Clin Auton Res (2012) 22:207258 DOI 10.

1007/s10286-012-0175-5

ABSTRACTS

23rd INTERNATIONAL SYMPOSIUM ON THE AUTONOMIC NERVOUS SYSTEM

Atlantis Resort Paradise Island, Bahamas October 31November 3, 2012 Preliminary Program
WEDNESDAY, OCTOBER 31, 2012 6:007:00 PM 7:007:15 PM Registration Imperial Foyer South I WelcomeDr. Michael Joyner, President Imperial Ballroom CD

Autonomic Failure: PAF, MSA, Parkinsons Disease Chairs: Eduardo Benarroch & Steven Vernino
7:157:30 PM Alpha synuclein as a cutaneous biomarker of Parkinson disease C.H. Gibbons, N. Wang, J. Lafo, R. Freeman Boston, MA, USA CSF biomarkers of central and peripheral catecholamine deciency in synucleinopathies D.S. Goldstein, L. Sewell, C. Holmes, C. Sims-ONeil, Y. Sharabi Bethesda, MD, USA Prognostic indicators and clinical spectrum of MSA based on autopsy-conrmed cases J.J. Figueroa, A.K. Parsaik, W. Singer, P. Sandroni, E.E. Benarroch, P.A. Low, J.H. Bower Rochester, MN, USA Mechanical stimulation of the feet improves gait and increases cardiac vagal prole in Parkinsons disease F. Barbic, M. Galli, M. Canesi, A. Porta, V. Cimolin, V. Bari, L. Dalla Vecchia, F. Dipaola, V. Pacetti, F. Meda, I. Bianchi, E. Brunetta, R. Furlan Milan, Italy Profound myocardial catecholamine depletion in Lewy body diseases D.S. Goldstein, P. Sullivan, T. Jenkins, C. Holmes, M. Basile, D.C. Mash, I.J. Kopin, Y. Sharabi Bethesda, MD, USA Autonomic dysfunction in Parkinsonian LRRK2 mutation carriers mez Esteban, K. Berganzo, V. Llorens, H.J.J. Zarranz B. Tijero, J.C. Go Bilbau, Spain Comparison of techniques for non-invasive assessment of systemic hemodynamics in autonomic function testing C. Sims-ONeil, S. Pechnik, L. Sewell, L. Nez, D.S. Goldstein Bethesda, MD, USA

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THURSDAY, NOVEMBER 1, 2012 7:308:00 AM Breakfast & Exhibits Imperial Ballroom B

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Clin Auton Res (2012) 22:207258 Plenary Lecture Master and commander: the brain and the autonomic nervous system Vaughan G. Maceeld, Ph.D University of Western Sydney & Neuroscience Research Australia Sydney, Australia

Cerebral Blood Flow, Neuroimaging in Brain and Heart & Pediatric Autonomic Disorders Chairs: Lucy Norcliffe-Kaufmann & Jens Tank
8:459:00 AM The middle cerebral artery dilates to sodium nitroprusside: a combined transcranial Doppler and near infrared spectroscopy study J.M Stewart, C.E. Schwartz, Z.R. Messer, C. Terilli, M.S. Medow, Valhalla, NY, USA Cerebral oxygenation, heart rate & blood pressure responses in congenital central hypoventilation syndrome (CCHS) during exogenous ventilatory challenges: PHOX2B genotype/CCHS phenotype association M.S. Carroll, P.P. Patwari, T.M. Stewart, C.D. Brogadir, A.S. Kenny, C.M. Rand, D.E. Weese-Mayer Chicago, IL, USA Time course of cardiac sympathetic denervation in Parkinson disease D.S. Goldstein Bethesda, MD, USA Parental attribution of symptoms in adolescents with postural tachycardia syndrome and its relation to child functioning and psychological variables E.M. Keating, R.M. Antiel, K.E. Weiss, D. Wallace, P.R. Fischer, C. Harbeck-Weber Rochester, MN, USA Cardiovagal sensitivity and orthostatic heart rate response in young patients with orthostatic intolerance W. Singer, A.K. Parsaik, E.E. Benarroch, P. Sandroni, P.A. Low Rochester, MN, USA Parental response to pain: the impact on functional disability, depression, anxiety, and pain acceptance in adolescents with chronic pain and orthostatic intolerance R.M. Antiel, E.M. Keating, K.E. Weiss, D.P. Wallace, P.R. Fischer, C. Harbeck-Weber Rochester, MN, USA Coffee Break Imperial Ballroom B

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Autonomic Regulation: Basic Science & Animal Studies Chairs: David Jardine & Imad Jarjour
10:3010:45 AM Relationship between ganglionic long-term potentiation (LTP) and homeostatic synaptic plasticity in experimental autoimmune autonomic ganglionopathy (EAAG) Z. Wang, S. Vernino Dallas, TX, USA Methionine sulfoxide reductase A: a novel molecular determinant of baroreex sensitivity, blood pressure and hypertensive end-organ damage R. Sabharwal, R. El Accaoui, M.K. Davis, J.A. Goeken, R. Weiss, F.M. Abboud, D. Meyerholz, M.W. Chapleau Iowa City, IA, USA Baroreex induced changes in stressed blood volume, not cardiac output curve, is the central mechanism preventing volume load induced pulmonary edema T. Sakamoto, T. Kakino, K. Sunagawa Fukuoka, Japan Prostaglandin D synthase is critical for development of chronic angiotensin II-salt hypertension in the rat G.D. Fink, N. Asirvatham-Jeyaraj East Lansing, MI, USA The central chemoreex activation induces sympathoexcitation and resets the arterial baroreex without compromising its pressure stabilizing function K. Saku, K. Sunagawa Fukuoka, Japan Advanced techniques and pitfalls of autonomic function assessment and arrhythmia analysis in the mouse model C.M. Welzig, J.B. Galper Charleston, SC, USA Lunch & Poster Session I Imperial Ballroom B Free Time AAS Business meeting Imperial Ballroom CD

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Awards Session Chairs: Michael Joyner & Wouter Wieling

4:004:45 PM Streeten Lecture The ups and downs of blood pressure & baroreex sensitivitya historical and personal perspective Mark Chapleau, Ph.D University of Iowa and Veterans Affairs Medical Center, Iowa City, IA, USA Streeten Travel Fellowship Award Blunted osmopressor response in familial dysautonomia N. Goulding, L. Norcliffe-Kaufmann, J. Martinez, D. Roncevic, L. Stok, F. Axelrod, H. Kaufmann New York, NY, USA FMS/Penaz Wesseling Award Paradox elevations in angiotensin II, independent of plasma renin activity, contribute to the supine hypertension of primary autonomic failure A.C. Arnold, L.E Okamoto, C. Shibao, A. Gamboa, S.R. Raj, D. Robertson, I. Biaggioni Nashville, TN, USA FMS/Penaz Wesseling Award Chronic effects of aliskiren versus hydrochlorothiazide on sympathetic neural responses to head-up tilt in hypertensive seniors Y. Okada, S.S. Jarvis, S.A. Best, T.B. Bivens, R.L. Meier, B.D. Levine, Q. Fu Dallas, TX, USA AAS Travel Award Association between cerebral autoregulation and white matter hyperintensities in elderly individuals S. Purkayastha, B. Paccha, I. Iloputaife, D.K. Kiely, F.A. Sorond, L.A. Lipsitz Roslindale, MA, USA AAS Travel Award The change in arterial stiffness during ganglionic blockade is associated with sympathetic nerve activity in women J.N. Barnes, R.E. Harvey, E.C. Hart, N. Charkoudian, T.B. Curry, J.H. Eisenach, W.T. Nicholson, M.J. Joyner, D.P. Casey Rochester, MN, USA

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FRIDAY, NOVEMBER 2, 2012 7:007:30 AM 7:308:15 AM Breakfast & Exhibits Imperial Ballroom B Plenary Lecture Autonomic responses to pregnancy Qi Fu, M.D., Ph.D Institute for Exercise and Environmental Medicine, Texas Health Presbyterian Hospital Dallas, and UT Southwestern Medical Center, Dallas, TX, USA

Microneurography & Cardiovascular Control in Humans/Cardiovascular Disease, Diabetes, Obesity & Aging Chairs: Jill Barnes & Qi Fu
8:158:30 AM Catheter based renal nerve ablation does not elicit a central sympatholytic response in difcult to control hypertensive patients J. Brinkmann, K. Heusser, B.M. Schmidt, J. Menne, G. Klein, H. Haller, A. Diedrich, J. Jordan, J. Tank Hanover, Germany Methodological considerations for assessing resting spontaneous baroreex control of muscle sympathetic nerve activity in humans S.W. Holwerda, H. Yang, J.R. Carter, P.J. Fadel Columbia, MO, USA Sleep deprivation augments cardiovascular reactivity to acute stress in humans H. Yang, J.J. Durocher, R.A. Larson, J.P. DellaValla, J.R. Carter Houghton, MI, USA Susceptibility to inducible ventricular arrhythmia in type I diabetic Akita mice is dependent on abnormalities of Ca2+ handling H. Jin, M. Rajab, M. Aronovitz, B. Wang, K. Picard, H. Park, M. Link, J.B. Galper Boston, MA, USA Sympathetic hyper-responsiveness In takotsubo cardiomyopathy L. Norcliffe-Kaufmann, J. Martinez, H. Kaufmann, H. Reynolds New York, NY, USA

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Clin Auton Res (2012) 22:207258 Improvement of obesity-associated insulin resistance during autonomic blockade A. Gamboa, L. Okamoto, A. Arnold, S. Raj, A. Diedrich, N. Abumrad, I. Biaggioni Nashville, TN, USA Coffee & Poster Session II Imperial Ballroom B

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Postural Orthostatic Tachycardia Syndrome (POTS) Chairs: Satish Raj & Wolfgang Singer
11:1511:30 AM Beta-2 adrenergic receptor polymorphism and hemodynamics in patients with postural orthostatic tachycardia syndrome and healthy controls M.N. Manento, L.R. Gullixson, K.K. Nickander, P.A. Low, J.H. Eisenach Rochester, MN, USA The pathophysiology of neuropathic and non-neuropathic postural tachycardia syndrome C. Gibbons, I. Bonyhay, A. Benson, R. Freeman Boston, MA, USA Deconditioning in patients with orthostatic intolerance A. Parsaik, T.G. Allison, W. Singer, D.M. Sletten, M.J. Joyner, E.E. Benarroch, P.A. Low, P. Sandroni Rochester, MN, USA Preliminary data on the durability of improved symptoms, functioning, and psychological distress in adolescents with POTS treated in a multidisciplinary treatment program B.K. Bruce, T.E. Harrison, K.E. Weiss, P.R. Fischer, S.P. Ahrens, W.N. Timm Rochester, MN, USA Objective measures of sleep in patients with POTS S.J. Kizilbash, P.R. Fischer, R.M. Lloyd Rochester, MN, USA Reduced alpha-adrenergic vascular response: the physiological link between postural orthostatic tachycardia syndrome and neurally mediated syncope N. Mehta, M. Tavora-Mehta, J.C. Guzman, C.A. Morillo Hamilton, ON, Canada Free Time Presidential Dinner Ripples Pool Deck SATURDAY, NOVEMBER 3, 2012 7:308:00 AM Breakfast & Exhibits Imperial Ballroom B

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Diabetic, Autoimmune & Other Autonomic Neuropathies Chairs: Christopher Gibbons & Christoph Schroeder
8:008:15 AM Multi-scale glycemic variability affects brain structure and functional outcomes in type 2 diabetes mellitus X. Cui, A. Galica, B. Manor, A. Abduljalil, C.-K. Peng, V. Novak Boston, MA, USA The laser Doppler imaging axon-reex are areaa novel regression thresholding based technique to assess neurovascular function T. Siepmann, B.M. Illigens, R. Freeman, C. Gibbons Boston, MA, USA Long-term outcomes in autoimmune autonomic ganglionopathy S. Muppidi, E.B. Spaeth, C. Gibbons, S. Vernino Dallas, TX, USA Type I diabetic Akita mice demonstrate decreased heart rate variability and increased inducibility of ventricular tachycardia which are reversed by statins C.M. Welzig, H.-J. Park, M. Rajab, M. Aronovitz, H. Jin, M.S. Link, J.B. Galper Charlston, SC, USA The quantication of sudomotor nerve bers: a multicenter study in diabetes C.H. Gibbons, J. Lafo, G. Smith, R. Singleton, R. Freeman Boston, MA, USA Coffee & Poster Session III Imperial Ballroom B

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Orthostatic Hypotension and Syncope Chairs: Rasna Sabharwal & Darren Casey
10:4511:00 AM Treatment of neurogenic orthostatic hypotension (NOH) with droxidopa: results from a multicenter, double-blind, randomized, placebo-controlled, parallel group, induction design study H. Kaufmann, P. Low, I. Biaggioni, C.J. Mathias, R. Freeman, L.A. Hewitt New York, NY, USA What is MSNA doing at the onset of syncope? D.L. Jardine Christchurch, New Zealand A meta-analysis of pharmacologic treatments of orthostatic hypotension C.H. Gibbons, S. Raj Boston, MA, USA Increasing cardiac output does not change middle cerebral artery blood velocity in the hyperthermic human C.G. Crandall, T. Seifert, T.E. Wilson, M. Bundgaard-Nielsen, N.H. Secher Dallas, TX, USA Patterns of diagnosis and intervention in neurogenic orthostatic hypotension (NOH): a patient-ow study H. Kaufmann, R.E. Paquette New York, NY, USA Open Discussion & Adjourn

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POSTER SESSION I Thursday, November 1, 2012

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Autonomic Failure: PAF, MSA, Parkinsons Disease

Poster #1 A randomized, double-blind, placebo-controlled clinical trial of Rifampicin in multiple system atrophy P.A. Low, S. Gilman, D. Robertson, I. Biaggioni, W. Singer, H. Kaufmann, S. Perlman, W. Cheshire, S. Vernino, R. Freeman, R.A. Hauser, S. Lessig Rochester, MN, USA Orthostatic hypotension in Parkinson disease: passive tilt vs. active standing J. Martinez, J.C. Esteban Gomez, B. Tijero Merino, K. Berganzo, H. Kaufmann New York, NY, USA Cerebellar and parkinsonian phenotypes in multiple system atrophy (MSA). Similarities and differences D. Roncevic, J. Martinez, L. Norcliffe-Kaufmann, H. Kaufmann New York, NY, USA A novel quantitative index of baroreex-sympathoneural function: application to patients with chronic autonomic failure F. Rahman, D.S. Goldstein Bethesda, MD, USA Loss of cerebral blood ow rhythm in Parkinsons disease and vascular parkinsonism S.-J. Yeh, B.-W. Chang, B.-Y. Liau, C.-C. Chiu Taichung, Taiwan

Poster #2

Poster #3

Poster #4

Poster #5

Pediatric Autonomic Disorders

Poster #6 Temperature prole in congenital central hypoventilation syndrome (CCHS) and rapid-onset obesity with hypothalamic dysfunction, hypoventilation, and autonomic dysregulation (ROHHAD): ibutton measures of peripheral skin temperature R. Saiyed, C.M. Rand, M.S. Carroll, P.P. Patwari, T. Stewart, C. Koliboski, D.E. Weese-Mayer Chicago, IL, USA Heart rate variability in hospitalized children: autonomic response to laughter and engagement P.P. Patwari, M.S. Carroll, K. Gray, M.K. Janda, A.S. Kenny, T.H. Stewart, C. Brogadir, S.H. Wang, D.M. Steinhorn Chicago, IL, USA Cardiac stroke volume and sympathetic/parasympathetic measurements increase the sensitivity and specicity of HUTT in children and adolescents M.T. Numan, J.E. Lankford, A. Gourishankar, I.J. Butler Houston, TX, USA

Poster #7

Poster #8

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Autonomic Regulation: Basic Science & Animal Studies

Poster #9 Biogenic amine metabolism in juvenile neurocardiogenic syncope with dysautonomia I.J. Butler, J.E. Lankford, M.T. Numan Houston, TX, USA The iceman revisited: autonomic function tests during performance of the Asian Tummo meditation technique J.T. Groothuis, M.T.E. Hopman Nijmegen, The Netherlands Evidence for central sensitization in bladder pain syndrome from the ICEPAC trial (Interstitial Cystitis: Elucidation of Psychophysiologic and Autonomic Characteristics)preliminary psychometric ndings J.W. Janata, F. Daneshgari, C.A.T. Bufngton, G. Chelimsky, M.D. Louttit, D. Zhang, T.C. Chelimsky Cleveland, OH, USA

Poster #10

Poster #11

Novel Therapies & Clinical Trials

Poster #12 The antiemetic efcacy of carbidopa: a randomized, double-blind, placebo-controlled crossover study in patients with familial dysautonomia L. Norcliffe-Kaufmann, J. Martinez, F. Axelrod, H. Kaufmann New York, NY, USA Comparative efcacy between the norepinephrine transporter blocker, atomoxetine, against midodrine for the treatment of orthostatic hypotension C.E. Ramirez, L.E. Okamoto, A. Gamboa, S.R. Raj, A. Diedrich, D. Robertson, I. Biaggioni, C. Shibao Nashville, TN, USA Benecial effects of oral rehydration solution on orthostatic intolerance M.S. Medow, D. Tewari, A. Aggarwal, Z. Messer, J.M. Stewart Valhalla, NY, USA

Poster #13

Poster #14

Gastrointestinal & Urogenital Systems, IBS, Cystitis

Poster #15 Musculoskeletal evaluation of patients with interstitial cystitis T.V. Sanses, G. Chelimsky, D. Zhang, J. Janata, T. Mahajan, B. Fenton, A. Askari, R. Elston, T. Chelimsky, ICEPAC Study Group Milwaukee, WI, USA Heart rate variability in pelvic pain P. Singh, J. Thayer, G. Chelimsky, T. Chelimsky Milwaukee, WI, USA Study of the P2X2 and 7 receptors in the enteric glial cells of ileum rat subjected to ischemia and reperfusion C.E. Mendes, K. Palombit, W. Tavares de Lima, P. Castelucci o Paulo, Brazil Sa Brainstem neuropeptides and vagal protection of the gastric mucosal against injury: role of prostaglandins, nitric oxide and calcitonin-gene related peptide in capsaicin afferents Y. Tache Los Angeles, CA, USA Autonomic dysfunction and esophageal dysmotility in persons with spinal cord injury G.J. Schilero, M. Radulovic, C. Renzi, C. Yen, W.A. Bauman, M. Korsten Bronx, NY, USA Real time change of prefrontal cortex activity related to normal and abnormal bladder lling in Parkinson disease: a functional near-infrared spectroscopy (fNIRS) study C. Yamaguchi, T. Uchiyama, T. Yamamoto, R. Sakakibara, M. Fuse, M. Yanagisawa, T. Kamai, T. Ichikawa, K. Hirata, S. Kuwabara, T. Yamanishi Tochigi, Japan Effect of Brilliant Blue G on P2X7 receptor after intestinal ischemia and reperfusion K. Palombit, C.E. Mendes, W. Tavares de Lima, P. Castelucci Sao Paulo, Brazil Photo-stimulating effects of low reactive level laser on bladder dysfunction in neurological disease rats T. Uchiyama, C. Yamaguchi, T. Yamamoto, R. Sakakibara, M. Fuse, M. Yanagisawa, T. Kamai, T. Ichikawa, K. Hirata, S. Kuwabara, T. Yamanishi Tochigi, Japan

Poster #16

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Poster #21

Poster #22

Cerebral Blood Flow Regulation

Poster #23 Cerebral blood ow in autonomic failure L. Rivera Lara, P. Novak Worcester, MA, USA

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Added clinical value of cerebral blood ow in juveniles and young adults with neurocardiogenic syncope and dysautonomia as measured by near-infrared spectroscopy J.E. Lankford, M.T. Numan, A. Gourishankar, I.J. Butler Houston, TX, USA

POSTER SESSION II Friday, November 2, 2012

9:4511:15 AM

Microneurography & Cardiovascular Reexes in Humans

Poster #25 Do the chronic heart failure patients have limited sympathetic response to a transient baroreex stress? P. Zubin Maslov, T. Breskovic, J.K. Shoemaker, Z. Dujic Split, Croatia Assessment of cardiovascular adrenergic function using the Valsalva maneuverreproducibility and validity of indices T.L. Gehrking, J.A. Gehrking, J.D. Schmelzer, P.A. Low, W. Singer Rochester, MN, USA Sex differences in limb vascular reactivity to mental stress in humans J.R. Carter, H. Yang, T.D. Drummer Houghton, MI, USA Melatonin does not alter skin sympathetic nerve responses to mental stress C.A. Ray, C.L. Sauder, M.D. Muller Hershey, PA, USA The arterial baroreex resets with orthostasis C.E. Schwartz, J.M. Stewart Hawthorne, NY, USA Carotid chemoreex and muscle metaboreex interactions in humans H. Edgell, M.K. Stickland Edmonton, AB, Canada Do multi-unit sympathetic discharge patterns change with age and cardiovascular disease? D.N. Brewer, P. Zubin Maslov, Z. Dujic, J.K. Shoemaker London, Ontario, Canada

Poster #26

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Poster #28

Poster #29

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Poster #31

Cardiovascular Disease, Obesity & Aging: Human Studies

Poster #32 Acute baroreex sensitivity impairment due to insulin-induced experimental hypoglycemia A. Rao, I. Bonyhay, S. Ballatori, G. Adler, R. Freeman Boston, MA, USA Autonomic contribution to blood pressure and resting energy expenditure in obese hispanics L.E. Okamoto, C. Shibao, A. Gamboa, A. Diedrich, G. Farley, S. Paranjape, I. Biaggioni Nashville, TN, USA The impact of injury to autonomic pathways on cardiovascular disease risk after spinal cord injury H.J.C. Ravensbergen, I.S. Sahota, S.A. Lear, V.E. Claydon Burnaby, British Columbia, Canada What is the best marker for obesity in individuals with spinal cord injury? H.J.C. Ravensbergen, M.C. Keenleyside, S.A. Lear, V.E. Claydon Burnaby, British Columbia, Canada Central arterial stiffness and autonomic modulation in active women P. Latchman, G. Gates, J. Pereira, R. Axtell, M. Bartels, R. De Meersman New Haven, CT, USA Impaired autonomic modulation in acute stroke improves with clinical recovery within 72 hours M.J. Hilz, H. Marthol, S. Moeller, J. Koehn, A. Akhundova, P. De Fina, S. Schwab Erlangen, Germany & New York, NY, USA Relation of cardiovagal baroreex sensitivity to impaired carotid artery elastic function in patients with tetralogy of Fallot A. Pinter, T. Horvath, A. Sarkozi, D. Cseh, M. Kollai Budapest, Hungary Features of vascular neurogenic regulation in patients with atrial brillation and heart failure O.V. Mamontov, A.V. Kozlenok, E.R. Bernhard, E.V. Parmon, E.V. Shlyakhto Saint-Petersburg, Russian Federation Calcitonin gene related peptide level and endocannabinoid system activity in patients with abdominal obesity and arterial hypertension E. Shlyakhto, E. Bazhenova, O. Belyaeva, A. Berezina, O. Berkovich, E. Baranova Saint-Petersburg, Russian Federation

Poster #33

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Poster #36

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Clin Auton Res (2012) 22:207258 Heart rate variability and high sensitivity C-reactive protein: inuence of coronary artery lesions N.Y. Tamburus, V.C. Kunz, R.F.L. Paula, M.R. Salviati, T.A.G. Nery, E. da Silva o Paulo, Brazil Sa

Sympathovagal Balance & Spectral Analysis

Poster #42 Oligober recordings detail single-ber sympathetic nerve discharge C.-K. Su, C.-H. Chiang, C.-M. Ho, C.-M. Lee, Y.-P. Fan Taipei, Taiwan Cardiovascular autonomic control in the rst year after spinal cord injury J. Inskip, M. McGrath, B. Kwon, V. Claydon Burnaby, BC, Canada Sympathovagal balancea thermodynamic perspective R. Schondorf, J. Benoit, M.J. Latte Montreal, QC, Canada The autonomic testing of normal subjects G. Chelimsky, S.M. Ialacci, T.C. Chelimsky Milwaukee, WI, USA

Poster #43

Poster #44

Poster #45

Blood Flow & Autonomics

Poster #46 Alpha-adrenergic blockade unmasks a greater compensatory vasodilation in hypoperfused contracting muscle D.P. Casey, M.J. Joyner Rochester, MN, USA COMPASS 31a rened and abbreviated composite autonomic symptom score D.M. Sletten, G.A. Suarez, P.A. Low, J. Mandrekar, W. Singer Rochester, MN, USA Autonomic, Blood Flow and Sensory Small Fiber Scale (ABSS) P. Novak Worcester, MA, USA Systemic dysautonomia in complex regional pain syndromea feasibility study K.R. Chemali, K. McNeeley, L. Zhou, T. Chelimsky Norfolk, VA, USA

Poster #47

Poster #48

Poster #49

POSTER SESSION III Saturday, November 3, 2012

9:1510:45 AM

Exercise, Temperature Regulation & Hypoxia

Poster #50 Thermophysiological consequences of an absent evening melatonin release in spinal cord injury H. Jones, J.T. Groothuis, T.M.H. Eijsvogels, J. Nyakayiru, R.J.M. Verheggen, A. Thompson, E.J.W. van Someren, G. Atkinson, M.T.E. Hopman, D.H.J. Thijssen Nijmegen, The Netherlands Post-exercise recovery period in patients with idiopathic ventricular arrhythmias E. Parmon, T. Tulintseva, E. Berngardt, E. Panova, E. Shlaykto Saint Petersburg, Russian Federation

Poster #51

Postural Orthostatic Tachycardia Syndrome

Poster #52 Regulation of circulation during exercise in adolescents with postural orthostatic tachycardia syndrome (POTS) A. Goodloe, D. Soma, C.K. Brands, P.R. Fischer, P.T. Pianosi Rochester, MN, USA Neuropsychological proles in adolescents with postural tachycardia syndrome (POTS) K.D. Evankovich, L.K. Jarjour, A.M. Hernandez, I.T. Jarjour Houston, TX, USA How important is the T in POTS using pediatric versus adult diagnostic criteria for postural tachycardia? I.T. Jarjour, A.M. Hernandez, L.K. Jarjour Houston, TX, USA Palpitations in postural tachycardia syndrome: what do they tell? R.K. Khurana Baltimore, MD, USA The spectrum of neuropathic orthostatic tachycardia W. Singer, T.L. Gehrking, P.A. Low Rochester, MN, USA

Poster #53

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Poster #58

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Poster #61

Origins of cognitive dysfunction in postural tachycardia syndrome A.C. Arnold, K. Haman, E.M. Garland, S.Y. Paranjape, C.A. Shibao, I. Biaggioni, D. Robertson, S.R. Raj Nashville, TN, USA Pharmacological I(f) pacemaker current inhibition in a human postural tachycardia syndrome (POTS) model C. Schroeder, K. Heusser, D. Rieck, F.C. Luft, J. Tank, J. Jordan Hannover, Germany Cardiovascular autonomic response to nitric oxide inhibition in POTS patients I. Bonyhay, C. Gibbons, A. Benson, R. Freeman Boston, MA, USA Postural tachycardia syndrome: optimal duration of diagnostic orthostatic challenge W.B. Plash, V. Nwazue, A. Diedrich, I. Biaggioni, E.M. Garland, S.Y. Paranjape, B.K. Black, W.D. Dupont, C. Shibao, S.R. Raj Nashville, TN, USA Uncoupling of serum interleukin-6 and C-reactive protein in lean patients with postural tachycardia syndrome L.E. Okamoto, S.R. Raj, A. Gamboa, C. Shibao, A.C. Arnold, A. Diedrich, G. Farley, D. Robertson, I. Biaggioni Nashville, TN, USA

Orthostatic Hypotension & Syncope

Poster #62 Blood pressure effect of droxidopa in hypotensive individuals with spinal cord injury J. Wecht, D. Rosado-Rivera, C. Yen, M. Radulovic, W. Bauman Bronx, NY, USA Prevalence of orthostatic hypotension in asymptomatic veterans J. Wecht, C. Yen, S. Pena, A. Ivan, W. Bauman Bronx, NY, USA Combination ergotamine and caffeine for the treatment of orthostatic hypotension C. Shibao, C.E. Ramirez, L.E. Okamoto, A.C. Arnold, A. Gamboa, P. Muppa, S.R. Raj, A. Diedrich, D. Robertson, I. Biaggioni Nashville, TN, USA Abnormal autonomic ndings in chronic subjective dizziness: sympathetic dysfunction or hyperactivity H. Lee, H.A. Kim Daegu, South Korea Neurogenic mechanisms and venous physiology in patients with orthostatic intolerance L. Saju, Z. Sun, R. Shields, F. Fouad-Tarazi Cleveland, OH, USA Mechanisms underlying the relationships between cardiovascular dysfunction and fall susceptibility in older adults B.H. Shaw, S.N. Robinovitch, V.E. Claydon Burnaby, BC, Canada Arterial baroreex asymmetry: an additional mechanism of orthostatic insufciency in patients with non-cardiac syncope O.V. Mamontov, M.I. Bogachev, E.V. Shlyakhto Saint-Petersburg, Russian Federation Myoclonic jerks in syncope are probably generated in the cortex J.G. van Dijk, R.D. Thijs, J. van Niekerk, W. Wieling, D.G. Benditt Leiden, The Netherlands

Poster #63

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Poster #66

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Poster #69

Diabetic, Autoimmune & Other Autonomic Neuropathies

Poster #70 Glucoregulation and autonomic function in older male patients with diabetes mellitus and obstructive sleep apnea J.L. Gilden, J. Cheng, B. Theckedath, P. Hung, J. Stoll North Chicago, IL, USA A case of paraneoplastic autonomic failure preceding Hodgkins lymphoma P. Muppa, C.E. Ramirez, B. Black, D. Robertson, A. Peltier, S.R. Raj, C. Shibao, I. Biaggioni Nashville, TN, USA 11-year follow-up of a case of autoimmune autonomic ganglionopathy W. Singer, D.M. Sletten, T.L. Gehrking, A.K. Parsaik, P.A. Low Rochester, MN, USA Autonomic function test outcomes in diabetes mellitus L.B. Tay, S. Srinivasan, C. Kang, T. Umapathi Singapore

Poster #71

Poster #72

Poster #73

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Clin Auton Res (2012) 22:207258 (PAF), and Parkinson disease (PD). We hypothesized that cerebrospinal uid levels of neuronal metabolites of catecholamines provide neurochemical biomarkers of these disorders. Methods: We measured cerebrospinal uid levels of catechols including dopamine, norepinephrine, and their main respective neuronal metabolites dihydroxyphenylacetic acid and dihydroxyphenylglycol in MSA, PAF, and PD. Cerebrospinal uid catechols were assayed in 146 subjects54 MSA, 20 PAF, 34 PD, and 38 controls. In 14 patients cerebrospinal uid was obtained before or within 2 years after the onset of Parkinsonism. Results: The MSA, PAF, and PD groups all had lower cerebrospinal uid dihydroxyphenylacetic acid [1.32 (SEM) 0.12 nmol/l, 0.86 0.09, 1.00 0.09] than controls (2.15 0.18 nmol/l; p \ 0.0001, p = 0.0002, p \ 0.0001). Dihydroxyphenylglycol was also lower in the three synucleinopathies (7.75 0.42, 5.82 0.65, 8.82 0.44 nmol/l) than controls (11.0 0.62 nmol/l; p = 0.009, p \ 0.0001, p \ 0.0001). Dihydroxyphenylacetic acid was lower and dihydroxyphenylglycol higher in PD than in PAF. Dihydroxyphenylacetic acid was 100 % sensitive at 89 % specicity in separating patients with recent onset of Parkinsonism from controls but was of no value in differentiating MSA from PD. Conclusions: Synucleinopathies feature cerebrospinal uid neurochemical evidence for central dopamine and norepinephrine deciency. PD and PAF involve differential central dopaminergic versus noradrenergic lesions. Cerebrospinal uid dihydroxyphenylacetic acid seems to provide a sensitive means to identify even early PD. (Ref.: Goldstein et al., Brain 2012; Mar 26. [Epub ahead of print])

Wednesday, October 31, 2012 Oral Presentations Alpha-synuclein as a cutaneous biomarker of Parkinson disease
C.H. Gibbons, N. Wang, J. Lafo, R. Freeman Department of Neurology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA Background: Parkinsons disease is a multisystem neurodegenerative disease characterized by the deposition of a-synuclein in the central, peripheral and enteric nervous system. Although the most prominent manifestations of Parkinsons disease are due to central, motor system neurodegeneration, there is widespread peripheral, autonomic and enteric nervous system degeneration with associated clinical features. Objective: To develop a biomarker for Parkinson disease. Methods: Fourteen patients with Parkinson disease and 10 age and gender matched control subjects underwent skin biopsies at the distal leg, distal thigh and proximal thigh. Skin biopsies were stained for PGP9.5, tyrosine hydroxylase, vasoactive intestinal peptide and a-synuclein. The density of nerve bers within specic dermal organelles (pilomotor muscles and sweat glands) was calculated. Because normal subjects have low levels of a-synuclein and Parkinsonian subjects have autonomic nerve degeneration, we chose a primary outcome as the proportion of these nerve bers that contained a-synuclein (determined by a-synuclein overlap with PGP 9.5), dened as the a-synuclein ratio. Results: Patients with PD had a distal sensory and autonomic neuropathy expressed by loss of intra-epidermal, pilomotor and sudomotor bers (P \ 0.05 vs. controls). Patients with PD had higher a-synuclein ratios compared to controls within pilomotor nerves at the distal leg (0.76 0.19 vs. 0.26 0.13, P \ 0.001), distal thigh (0.78 0.16 vs. 0.28 0.18; P \ 0.001) and proximal thigh (0.80 0.13 vs. 0.32 0.15; P \ 0.001). Patients with PD had higher a-synuclein ratios compared to controls within sudomotor nerves at the distal leg (0.20 0.11 vs. 0.02 0.01, P \ 0.005), distal thigh (0.18 0.12 vs. 0.02 0.01, P \ 0.005) and proximal thigh (0.20 0.14 vs. 0.02 0.01, P \ 0.005). Discussion: We have developed novel techniques to quantify the density of autonomic nerve ber innervation within specic dermal organelles, and have quantied the ratio of a-synuclein deposition within these nerve bers. We found signicantly elevated a-synuclein deposition ratios within both sympathetic adrenergic pilomotor and sympathetic cholinergic sudomotor bers in patients with Parkinson disease. These ndings suggest the a-synuclein ratio may be a biomarker in patients with Parkinson disease. Acknowledgement: Study supported by NIH NINDS K23NS050209 (CHG) and the RJG Foundation (CHG).

Prognostic indicators and clinical spectrum of MSA based on autopsy-conrmed cases

J.J. Figueroa, A.K. Parsaik, W. Singer, P. Sandroni, E.E. Benarroch, P.A. Low, J.H. Bower Department of Neurology, Mayo Clinic, Rochester, MN, USA Multiple system atrophy (MSA) is a progressive neurodegenerative disorder characterized by motor dysfunction with autonomic failure. The goal of our study was to evaluate phenotype at presentation, rate of motor deterioration, and survival time after onset of motor and autonomic symptoms in a cohort of autopsy conrmed MSA patients. We retrospectively studied the Mayo Clinic cohort of 49 autopsy conrmed MSA patients comprised of 33 (67 %) men and 16 (33 %) women. Disease duration from motor symptom onset (age 55.8 7.1 years) to death (age 65.5 8.6 years) was 9.7 4.7 years. Clinical phenotype at rst evaluation was MSA-P in 29 (60 %), MSA-C in 16 (32 %), MSA-PC in 2 (4 %), and pure autonomic failure in 2 (4 %). At presentation, patients had symmetric parkinsonism (27/32), retropulsion (12/14), absent resting tremor (37/44), poor levodopa responsiveness (18/22) and antecollis (5/7). Gait impairment was present at onset of motor symptoms in 80 %. Time from onset of motor symptoms to rst fall, wheelchair dependency and dysphagia was 1.5 0.8, 4.4 2.9 and 6.1 2.2 years respectively. Dysphagia requiring intervention was associated with the shortest survival time (1.4 1.2 years), followed by wheelchair dependency (4.4 2.9 years), fecal incontinence (6.0 3.8 years), presyncope and syncope (6.2 4.3 years), need for bladder catheterization (6.4 4.1 years) and erectile dysfunction (8.9 5.0 years). This study reveals important clinical characteristics and indicators of prognosis of MSA based on the natural history of a large cohort of well-characterized autopsy-conrmed cases of MSA.

CSF biomarkers of central and peripheral catecholamine deciency in synucleinopathies

D.S. Goldstein, L. Sewell, C. Holmes, C. Sims-ONeil, Y. Sharabi Clinical Neurocardiology Section, NINDS/NIH, Bethesda, MD, USA Background: Central catecholamine deciency characterizes primary chronic autonomic failure syndromes, including alpha-synucleinopathies such as multiple system atrophy (MSA), pure autonomic failure

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217 loss of catecholaminergic neurons both in the striatum and the heart, by assaying putamen and left ventricular apical concentrations of catecholamines and the catecholamine precursor DOPA, the immediate product of tyrosine hydroxylation, in post-mortem tissue from patients with PD, pure autonomic failure (PAF, a rare Lewy body disease that does not involve clinical evidence of central neurodegeneration), or multiple system atrophy (MSA, a non-Lewy body form of alpha-synucleinopathy). Methods: Putamen and apical myocardial tissue were obtained at autopsy within several hours of death in patients with end-stage PD, PAF, or MSA, and control patients (N = 4, 1, 1, and 6 as of this writing). Results: PD patients had strikingly decreased myocardial norepinephrine and dopamine contents (by 93 and 94 %) compared to controls (p = 0.008, p = 0.001). Decreased myocardial catecholamine contents were also evident in the PAF patient but were normal in the MSA patient. Myocardial and putamen DOPA were decreased in PD but to a lesser extent (about 2/3) than were the catecholamines. Post-mortem ndings conrmed neuroimaging and neurochemical data in the same patients during life. Conclusions: Lewy body diseases are associated with drastic myocardial catecholamine depletion, demonstrating that PD is not only a brain disease and movement disorder but is a more generalized disease that involves a form of dysautonomia. The decreases in norepinephrine and dopamine in the putamen and myocardium seem greater than explained by denervation alone, consistent with decreased vesicular storage in residual nerves.

Mechanical stimulation of the feet improves gait and increases cardiac vagal prole in Parkinsons disease
F. Barbic1, M. Galli2, M. Canesi3, A. Porta4, V. Cimolin2, V. Bari4, L. Dalla Vecchia5, F. Dipaola1, V. Pacetti1, F. Meda1, I. Bianchi1, E. Brunetta1, R. Furlan1 1 ` Sincopi e Disturbi della Postura, Clinica Medica-IRCCS Unita ` di Milano, Istituto Clinico Humanitas, Rozzano (MI), Universita Milano, Italy; 2Laboratorio per lanalisi della postura e del movimento L. Divieti, Politecnico di Milano, Milano, Italy; 3 Centro Parkinson, CTO, Milano, Italy; 4Dipartimento di Tecnologie ` di Milano, per la Salute, Istituto Ortopedico Galeazzi, Universita Milano, Italy; 5IRCCS, Fondazione Maugeri, Milano, Italy Background: Alterations in sensorimotor central integration and/or peripheral sensory function might play a role in movement disorders in Parkinsons disease (PD). Body mechanical stimulations was recently found to improve gait in PD. In addition, alterations in cardiovascular autonomic control are common in PD, although their relationships with movement disorders have not been fully addressed. Aims: We tested the hypothesis that bilateral plantar stimulation can improve gait and autonomic control of heart rate up to 24 h. Methods: We studied 13 patients with idiopathic PD (mean age 66 2 years, BMI 23 1 kg/m2, HoehnYahr scale 24) on their habitual pharmacological treatment. Every subject underwent mechanical pressure (0.8 kg/mm2) at the big toe tip and at the big toe metatarsal joint (plantar stimulation, PL) on both feet. Gait analysis and spectral analysis of heart rate variability provided quantitative indexes to assess movement disorders and cardiac autonomic prole (HFRR, marker of cardiac vagal modulation) before and 24 h after plantar stimulation. Results: Twenty-four hour after PL step mean length and gait velocity increased (23.3 6.2 from 537.7 40.8 mm and 0.06 0.02 from 0.93 0.09 m/s, respectively) and clock-wise rotation time decreased (-1.8 0.8 from 8.8 1.2 s). In addition, HFRR increased (1.2E-04 2.7E-04 from 4.5E-04 1.9E-04 m/sec2) compared to baseline, suggesting an enhancement of the cardiac vagal modulation. Conclusions: 24 h after plantar stimulation, PD patients showed changes in step length, gait velocity and body rotation time consistent with an improvement of their movement disorder. Plantar stimulation induced a concomitant increase in the vagal modulatory activity of heart rate.

Autonomic dysfunction in Parkinsonian LRRK2 mutation carriers

mez Esteban1, K. Berganzo1, V. Llorens2, B. Tijero1, J.C. Go H.J.J. Zarranz1 1 Movement Disorders and Autonomic Unit, Neurology Service, Cruces Hospital, Basque Health Service (Osakidetza), Department of Neurociences, University of the Basque Country, Spain; 2Nuclear Medicine Service, Cruces Hospital, Baracaldo, Spain Introduction: The aim of this study is to compare autonomic function in carriers of the LRRK2 (G2019S and R1441S) mutations and those with idiopathic Parkinsons Disease (iPD) Patients. Patients and methods: We studied 25 patients with a diagnosis of PD according to the UK Parkinsons Disease Society clinical diagnosis criteria (6 had the G2019S and 6 R1441G, and 13 had iPD without genetic mutations). All patients completed the SCOPA autonomic questionnaire, underwent blood pressure and heart rate monitoring during head up tilt with measurements of plasma norepinephrine, Valsalva maneuver and deep breathing, recording of sympathetic skin response (SSR), and cardiac MIBG scintigraphy. Results: Scores of the SCOPA questionnaire were similar in patients with and without the LRRK2 mutations. Three of the iPD and one of the LRRK2 carriers have orthostatic hypotension. During passive tilt, iPD patients have minor Blood pressure increase than LRRK patients. Arterial pressure overshoot during phase IV of the Valsalva maneuver was less pronounced in patients with iPD than LRRK2 mutation carriers. MIBG late (4 h) myocardial/mediastinal uptake ratios are higher in LRRK2 mutation carriers than iPD patients (1.51 0.28 vs. 1.32 0.25, p = 0.05) Discussion: Carriers of the LRRK2 gene mutation had less autonomic impairment than those with iPD as shown by higher cardiac MIBG uptake and less impairment of autonomic non-invasive test.

Profound myocardial catecholamine depletion in Lewy body diseases

D.S. Goldstein, P. Sullivan, T. Jenkins, C. Holmes, M. Basile, D.C. Mash, I.J. Kopin, Y. Sharabi Clinical Neurocardiology Section, NINDS/NIH, Bethesda, MD, USA Background: Striatal dopamine depletion is a neurochemical hallmark of Parkinson disease (PD) and a major cause of the characteristic movement disorder. Accumulating evidence indicates that PD and other Lewy body diseases also feature loss of cardiac sympathetic nerves, with decreased tyrosine hydroxylase, the rate-limiting enzyme in catecholamine biosynthesis, measured by semi-quantitative immunohistochemistry. We applied a quantitative neurochemical method to test whether Lewy body diseases characteristically involve

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Clin Auton Res (2012) 22:207258 increase in blood pressure that we may be worried about. The point here is that the delegated systemthe Commandercan operate without higher-order control to maintain our blood pressure, our heart rate, our temperature essentially constant. Yet, the Master can exert higher-order control that is either volitionally generated, such as during exercise or is the product of cognitive or affective processes, such as worrying or the experience of pain. In this talk, I will consider recent neuroimaging data that highlight the different roles of cortical and subcortical structures in the generation of sympathetic outow related to cardiovascular control. In particular, I will discuss the advantages of concurrent microneurography and functional magnetic resonance imaging (fMRI) in the identication of functional roles for various bulbar and suprabulbar structures, with particular reference to medullary and hypothalamic nuclei, the insula, precuneus and prefrontal cortex.

Comparison of techniques for non-invasive assessment of systemic hemodynamics in autonomic function testing
C. Sims-ONeil, S. Pechnik, L. Sewell, L. Nez, D.S. Goldstein Clinical Neurocardiology Section, NINDS/NIH, Bethesda, MD, USA Background: Neurogenic orthostatic hypotension is a cardinal manifestation of chronic autonomic failure (CAF). Systemic hemodynamic measurements include cardiac output (stroke volume times heart rate) and total peripheral resistance (TPR, mean arterial pressure divided by cardiac output). Normally, orthostasis decreases stroke volume, and heart rate and TPR increase reexively. In CAF, TPR should fail to increase during orthostasis, because of baroreex failure. This study compared three non-invasive methods for measuring orthostatic hemodynamic changes in CAF-impedance cardiography (BioZ), nger pulse contour (Nexn), and gas rebreathing (Innocor). Methods: A total of 78 subjects, 29 with and 49 without CAF, underwent simultaneous hemodynamic measurements by BioZ, Nexn, or Innocor during supine rest and at 5 min of head-up tilt. Results: Among supine subjects individual values by the three techniques agreed for stroke volume and TPR. CAF patients had higher TPR than did controls. During orthostasis, stroke volume decreased by all three measurements. Clear differences emerged for calculated orthostatic changes in TPR in CAF patients: BioZ reported a fall, Nexn no change, and Innocor an increase. In some patients, the Innocor rebreathing maneuver itself decreased stroke volume as indicated by the Nexn device, especially during orthostasis. Conclusions: All three non-invasive methods for tracking systemic hemodynamics yield similar results for TPR in supine subjects, and TPR during supine rest is increased in CAF. Impedance cardiography underestimates the orthostatic fall in stroke volume in CAF patients, resulting in a calculated orthostatic fall in TPR. Gas diffusion overestimates the orthostatic fall in stroke volume, resulting in a calculated orthostatic increase in TPR, due to artifactual effects of the rebreathing maneuver required for the cardiac output measurement. Of the three methods, the nger pulse contour approach seems to track most validly effects of orthostasis on TPR in CAF.

The middle cerebral artery dilates to sodium nitroprusside: a combined transcranial Doppler and near infrared spectroscopy study
J.M Stewart1,2, C.E. Schwartz1, Z.R. Messer2, C.Terilli2, M.S. Medow1,2 1 Department of Physiology, New York Medical College, Valhalla, NY, USA; 2Department of Pediatrics, New York Medical College, Valhalla, NY, USA Prior studies indicate that the middle cerebral artery (MCA) does not dilate in response to moderate orthostatic stress or changes in carbon dioxide. Thus, measurements of cerebral blood ow velocity (CBFv) by transcranial Doppler ultrasound (TCD) are sufcient to estimate relative changes in cerebral blood ow under these conditions. Systemically administered nitric oxide (NO) donors decrease CBFv. However, NO dilates cerebral arteries of all sizes in primate models. We investigated whether systemic bolus injection of the NO donor sodium nitroprusside (SNP) dilates the MCA and whether bolus phenylephrine constricts the MCA in 10 supine healthy volunteer subjects 1824 years old. We combined TCD of the MCA with near infrared spectroscopy (NIRS) over the frontal cortex. Cerebral oxygenation and total hemoglobin increased by 14 1 and 15 1 lM/L with 100 lg SNP despite hypotension, and were reduced by 6 1 and 7 1 lM with 150 lg phenylephrine despite hypertension. SNP increased NIRS derived cerebral blood ow estimates by approximately 40 % from baseline, while TCD derived CBFv decreased by 15 %. Phenylephrine decreased NIRS derived cerebral blood ow estimates by approximately 11 % from baseline, while TCD derived CBFv increased by 5 %. Studies using upright tilt and lower body negative pressure were performed for comparison with the literature and demonstrated similar relative changes in NIRS derived cerebral blood ow and TCD derived CBFv as orthostatic stress progressed. We conclude that the middle cerebral artery dilates to sodium nitroprusside and constricts to phenylephrine but does not dilate during orthostatic stress.

Thursday, November 1, 2012 Oral Presentations Plenary Lecture Master and commander: the brain and the autonomic nervous system
Vaughan G. Maceeld, Ph.D. School of Medicine, University of Western Sydney; Neuroscience Research Australia, Sydney, Australia The autonomic nervous system, so named because it operates automaticallywithout the need for conscious controlis very much a delegated system: it faithfully follows a set of instructions to bring about homeostasis, and attempts to maintain a stable internal environment in the presence of disease, yet these presets can be over-ridden by the requirements of higher-order control. We have all experienced the racing heart rate, and the cold, clammy palms associated with anxiety. Some of us may be in a state of chronic stress and are experiencing an

Cerebral oxygenation, heart rate & blood pressure responses in congenital central hypoventilation syndrome (CCHS) during exogenous ventilatory challenges: PHOX2B genotype/CCHS phenotype association
M.S. Carroll, P.P. Patwari, T.M. Stewart, C.D. Brogadir, A.S. Kenny, C.M. Rand, D.E. Weese-Mayer

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Clin Auton Res (2012) 22:207258 Center for Autonomic Medicine in Pediatrics, Ann and Robert H. Lurie Childrens Hospital, Northwestern University Feinberg School of Medicine, Chicago, IL, USA Congenital central hypoventilation syndrome (CCHS) is a disorder of respiratory and autonomic regulation, characterized by hypoventilation and diminished/absent ventilatory responses to hypoxia/ hypercarbia. However, ventilatory responses in CCHS have not been evaluated subsequent to identication of PHOX2B as the diseasedening gene, and recognition that the longer polyalanine repeat expansion mutations (PARMs) are typically associated with more severe clinical features. We therefore hypothesized that cerebral oxygenation and cardiovascular metrics in response to exogenous ventilatory challenges (EVC) would show a graded decit correlated with PHOX2B genotype among CCHS patients with PARMs. Thirtyone children and young adults (5 months27 years; 14 female) with CCHS were tested during wakefulness with 45 separate clinical EVCs (each with 4 distinct gas mixtures) during continuous comprehensive physiological monitoring. Three-minute challenges were administered between 3 min room-air periods, with minimal ventilatory support: Hyperoxia (100 % O2), hyperoxia-hypercarbia (95 % O2/ 5 % CO2) and hypoxia-hypercarbia (14 % O2/7 % CO2). The fourth challenge, hypoxia, consisted of 5 or 7 tidal breaths of N2. A comparison group of 4 young men (1821 years) were monitored while receiving all but the hypoxia challenge. Percent change from baseline (SEM) was calculated during each challenge for the cerebral near infrared spectroscopy (cNIRS) channel, mean blood pressure, and heart rate. Signicance was assessed at p \ 0.05 (paired t test). The 3 most common PARM genotypes were compared to assess genotypephenotype association. Though the cNIRS response was not consistently associated with polyalanine repeat length, it was impaired/ attenuated in CCHS versus controls during the hypoxia-hypercarbia challenge. Blood pressure responses were variable, but showed a CO2-dependent increase in CCHS. Heart rate was suppressed by hyperoxia in CCHS, but increased in the combined hypoxia-hypercarbia challenge. The heart rate response to the hypoxia-hypercarbia challenge was consistently correlated with polyalanine repeat length (blunted response with increasing PARM length). Overall, comprehensive physiological evaluation during ventilatory challenges indicated residual responsiveness in CCHS, providing a potential fulcrum for therapeutic interventions.

219 mean. Diffuse denervation was dened by both septal and free wall radioactivity more than 2 standard deviations below the normal mean. Results: The time between localized and diffuse denervation averaged 2.5 (SEM) 0.8 years. The mean change in septal radioactivity during this interval was -56 10 %, corresponding to 22 % loss per year. In one patient followed over more than 12 years, cardiac sympathetic innervation was normal for 6 years, with subsequent rapid loss of free wall radioactivity and then equally rapid loss of septal radioactivity with a delay of about 2 years. Conclusions: In Parkinson disease, once there is evidence for loss of sympathetic nerves in the left ventricular free wall, septal denervation rapidly ensues, resulting in remarkably swift diffuse denervation by 23 years later. Follow-up cardiac sympathetic neuroimaging in patients with localized cardiac denervation therefore may be a basis for a novel, quantitative means to assess potential treatments to retard the loss of catecholaminergic neurons that characterizes Parkinson disease.

Parental attribution of symptoms in adolescents with postural tachycardia syndrome and its relation to child functioning and psychological variables
E.M. Keating1, R.M. Antiel2, K.E. Weiss3, D. Wallace4, P.R. Fischer5, C. Harbeck-Weber3 1 Mayo Medical School, Mayo Clinic, Rochester, MN, USA; 2 Department of General Surgery, Mayo Clinic, Rochester, MN, USA; 3 Department of Psychiatry and Psychology, Mayo Clinic, Rochester, MN, USA; 4Integrative Pain Management, Childrens Mercy Hospital, Kansas City, MO, USA; 5Department of Pediatric and Adolescent Medicine, Mayo Clinic, Rochester, MN, USA Background: Chronic pain is a common symptom in adolescents with postural orthostatic tachycardia syndrome (POTS), and it is frequently associated with impairment in functioning. The manner in which parents respond to childrens pain may predict childrens functional disability, and parental responses to the pain are related to parental beliefs about the causes of the pain. The Parent Attribution Questionnaire (PAQ) was developed to assess these parental attributions regarding their childs pain. We evaluated parent attributions of symptoms in adolescents with POTS in order to determine how they are related to their childs functioning. Methods: 141 adolescent patients with chronic pain and clinical symptoms suggestive of POTS were seen in a multidisciplinary chronic pain clinic at Mayo Clinic. Of these patients, 37 were identied as having POTS with a postural heart range change of at least 40 beats per minute on tilt table testing. Parents of 114 of these patients completed a demographic questionnaire and PAQ. The PAQ is a 19-item questionnaire that asks parents to indicate the extent they believe medical (9 items) and psychosocial factors (10 items) account for their childs health condition. Results: In patients with chronic pain who have symptoms suggestive of possible autonomic dysfunction, higher parental attribution of symptoms to medical causes was associated with increased levels of functional disability (r = 0.33, p \ 0.001). Parental attribution of symptoms to psychological causes was linked to depression only in patients without POTS (r = 0.53, p \ 0.01) but not in those with POTS. Conclusions: Functional disability in adolescents with POTS relates to the degree to which parents attribute the childs symptoms to a medical problem. It is likely that helping parents avoid over-acceptance of incurable medical problems as causing pain could help children attain better functioning.

Time course of cardiac sympathetic denervation in Parkinson disease

D.S. Goldstein Clinical Neurocardiology Section, NINDS/NIH, Bethesda, MD, USA Background: Parkinson disease entails not only nigrostriatal dopaminergic but also cardiac noradrenergic denervation, which can occur before clinical onset of the movement disorder. The neuropathologic process in the heart appears to proceed retrogradely and centripetally. Localized denervation in the left ventricular myocardial free wall progresses to diffuse denervation, with late loss of interventricular septal innervation. We analyzed neuroimaging data from patients with localized denervation to estimate the loss rate of cardiac catecholaminergic neurons in Parkinson disease. Methods: Serial 18F-dopamine positron emission tomographic scanning data in Parkinson disease patients were reviewed and 4 patients identied who had localized followed by diffuse denervation. Localized denervation was dened by free wall 18F-dopamine-derived radioactivity more than 2 standard deviations below the normal mean and septal radioactivity within 2 standard deviations of the normal

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Clin Auton Res (2012) 22:207258 Background: Parental responses to pain may have an important impact on adolescent pain outcomes. Approximately 10 % of adolescents suffer from autonomic dysfunction marked by orthostatic intolerance, severe fatigue, and chronic pain. We sought to examine if parental responses to these symptoms are related to their childs functioning, psychological well-being, and pain acceptance. Methods: Participants included 141 adolescents with chronic pain and symptoms of orthostatic intolerance who were seen in a multidisciplinary pain clinic at the Mayo Clinic. Of the 141 patients, 37 (26 %) had excessive postural tachycardia (PT) with a heart rate change of at least 40 bpm on tilt table testing. Participants completed the Functional Disability Inventory, the Center of Epidemiological StudiesDepression Scale, the Spence Childrens Anxiety Scale, and the Chronic Pain Acceptance Questionnaire, adolescent version. Parents of 103 of these patients completed the Parent Response to Pain QuestionnaireRevised, which measures 4 theoretically driven parental factors: solicitous behaviors, secondary gain, promoting adaptive behavior, and encouragement of specic pain management. Results: Parent solicitous behaviors were signicantly related to anxiety (r = 0.21, p \ 0.05). Parent report of secondary gain was correlated with depression (r = 0.57, p \ 0.01) and negatively related to acceptance (r = -0.40, p \ 0.05). Upon further examination of the sub-sample of patients with excessive PT, parent report of secondary gain was related to functional disability (r = 0.39, p \ 0.05) and parent encouragement to use specic pain management skills was inversely associated with depression (r = -0.069, p \ 0.05). Conclusions: Differential parental responses to pain are signicantly related to adolescent anxiety, depression, and pain acceptance. Furthermore, in patients with co-morbid orthostatic intolerance parental responses are associated with functional disability and depression. These ndings suggest that parental responses to adolescent pain are related to patient outcomes and could have implications for effective interventions.

Cardiovagal sensitivity and orthostatic heart rate response in young patients with orthostatic intolerance
W. Singer, A.K. Parsaik, E.E. Benarroch, P. Sandroni, P.A. Low Department of Neurology, Mayo Clinic, Rochester, MN, USA Background and Objective: Orthostatic intolerance (OI) is increasingly recognized among adolescents but pathophysiologic mechanisms underlying this condition remain poorly understood. These patients typically have normal autonomic function as assessed using standardized autonomic testing. We frequently see high or very high values for cardiovagal indices in these patients and made the observation that those with unusually high HR responses to deep breathing (HRDB) and Valsalva maneuver (VM, Valsalva ratio = VR) also seem to have the most excessive HR responses to tilt. Such relationshipif presentwould be intriguing in terms of mechanisms underlying the magnitude of HR responses to tilt and of OI; factors such as excessive cardiac vagal modulation and baroreex sensitivity might be implicated. We therefore sought to evaluate whether the magnitude of cardiovagal indices predicts the orthostatic rise in HR and whether the pattern of ndings reveals insights into the pathophysiology underlying adolescent OI. Methods: 100 adolescent patients were randomly selected from a large cohort of patients referred to our laboratory for evaluation of symptoms of OI. HRDB and VR were quantied using standard techniques. Vagal baroreex sensitivity (vBRS) was dened as slope between systolic blood pressure (BP) decline during phase II and resulting change in RR interval. HR and BP responses to tilt were assessed using 30 s data averages, BP responses to the VM were assessed using systolic BP at the different phases of the maneuver. Correlations between different parameters were tested using Pearsons r. Results: HRDB and vBRS were not correlated with DHR or DBP during tilt. However, VR was signicantly correlated with DHR (p = 0.001). While VR was also strongly correlated with the BP changes during early phase II and phase IV of the VM, as well as the sum of both, only one of these BP indices (phase IV) was weakly correlated with DHR during tilt. No correlations were seen between BP and HR responses to tilt. Conclusions: These ndings argue against excessive cardiac vagal modulation or excessive BRS underlying the excessive orthostatic rise in HR in adolescents with OI. The pattern of ndings would rather suggest that the mechanism underlying the excessive orthostatic rise in HR also results in excessive BP responses to the VM and consequently excessive VR. This putative mechanism remains subject to further study. Supported by NIH (K23NS075141, U54NS065736, UL1RR24150) and Mayo Funds.

Relationship between ganglionic long-term potentiation (LTP) and homeostatic synaptic plasticity in experimental autoimmune autonomic ganglionopathy (EAAG)
Z. Wang, S. Vernino UT Southwestern University, Dallas, TX, USA The autonomic nervous system must be able to adapt to maintain homeostasis. Plasticity of ganglionic synaptic transmission represents one important mechanism of autonomic adaptation. We have shown that homeostatic plasticity of ganglionic neurotransmission occurs in EAAG. In EAAG, there is a reduction in synaptic ganglionic AChRs followed by a compensatory increase in neurotransmitter release to help offset the decit in synaptic transmission. Homeostatic plasticity is quite different from classical usedependent LTP. Both types of plasticity occur in autonomic ganglia, so the ganglionic synapse is an ideal system in which to study the interrelationship between these two forms of synaptic plasticity. We studied synaptic transmission in isolated mouse superior cervical ganglia using microelectrode and patch clamp electrophysiology methods. High frequency stimulation (HFS) of the preganglionic nerve (20 Hz for 20 s) in control ganglia induces a long-lasting increase in synaptic transmission due to increased probability of synaptic release. A second HFS does not produce further enhancement. Ganglia from mice with EAAG fail to show LTP. Inhibitors

Parental response to pain: the impact on functional disability, depression, anxiety, and pain acceptance in adolescents with chronic pain and orthostatic intolerance
R.M. Antiel1, E.M. Keating2, K.E. Weiss3, D.P. Wallace4, P.R. Fischer5, C. Harbeck-Weber3 1 Department of General Surgery, Mayo Clinic, Rochester, MN, USA; 2 Mayo Medical School, Rochester, MN, USA; 3 Department of Psychiatry and Psychology, Mayo Clinic, Rochester, MN, USA; 4Integrative Pain Management, Childrens Mercy Hospital, Kansas City, MO, USA; 5Department of Pediatric and Adolescent Medicine, Mayo Clinic, Rochester, MN, USA

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Clin Auton Res (2012) 22:207258 of nitric oxide synthase prevent the induction of LTP in control ganglia and also cause a normalization of presynaptic release in EAAG ganglia. These ndings indicate that homeostatic plasticity of synaptic transmission (as occurs in the EAAG model) shares common molecular mechanism with use-dependent plasticity (ganglionic LTP). The implication is that pharmacological manipulation of ganglionic LTP may be a useful therapeutic option for patients with autonomic disorders.

221 baroreex failure causes volume intolerance remains unknown. The aim of this investigation is to examine the mechanism of baroreex failure induced volume intolerance. Method: In 6 anesthetized dogs, we isolated carotid sinuses and controlled intra-carotid sinus pressure (CSP), while measuring the left (PLA) and right (PRA) atrial pressure, arterial pressure (AP) and aortic ow (CO). We closed the baroreex feedback loop by matching CSP to instantaneous AP, whereas opened by maintaining CSP constant independent of AP. We infused total of 22.5 ml/kg of dextran in an increment of 2.5 ml/kg. In each step, we measured PLA, PRA and CO in both open and closed loop conditions. We tted the CO curve to a logarithmic function and determined its functional slope S, as a measure of cardiac performance, for the left (SL) and right (SR) ventricle. We determined stressed blood volume and mean circulatory lling pressure (Pmcf). Results: Increases in PLA was lower in the closed loop than in the open loop condition (9 3 vs. 12 5 mmHg, p \ 0.05). Both SL and SR were lower in the closed loop than in the open loop condition (SL: 23 5 vs. 27 6 ml/kg/min, p \ 0.01, SR: 23 5 vs. 27 6 ml/kg/min, p \ 0.01) indicating that the baroreex lowers cardiac performance against volume overload. Pmcf after infusion of 22.5 ml/kg of dextran was lower in the closed loop than in the open loop condition (10.8 0.5 vs. 12.8 1.1 mmHg, p \ 0.005). Conclusion: In response to volume challenge, the baroreex lowered cardiac performance and prevented the increases in Pmcf. Although those two responses have antagonizing impact on PLA, the fact that the baroreex lowered PLA indicates that the baroreex induced changes in stressed volume is the central mechanism preventing pulmonary edema.

Methionine sulfoxide reductase A: a novel molecular determinant of baroreex sensitivity, blood pressure and hypertensive end-organ damage
R. Sabharwal, R. El Accaoui, M.K. Davis, J.A. Goeken, R. Weiss, F.M. Abboud, D. Meyerholz, M.W. Chapleau The University of Iowa and Veterans Affairs Medical Center, Iowa City, IA, USA Methionine sulfoxide reductase-A (MsrA) selectively reverses oxidation of methionine residues in proteins, thereby protecting against oxidative stress-induced cellular damage and dysfunction. We hypothesized that MsrA is required for normal autonomic and blood pressure (BP) regulation, and protects against hypertension-induced end-organ damage. BP, heart rate (HR) and locomotor activity were measured in MsrA decient (n = 13) and control C57BL/6 (n = 7) mice by telemetry, before and during infusion of angiotensin II (Ang II) (1,000 ng/kg/min for 4 weeks). Under basal conditions, MsrA-/mice exhibited mild hypertension (117 3 vs. 107 2 mmHg) and decreased locomotor activity. During periods when activity levels were similar, the hypertension in MsrA-/- mice was exacerbated (135 2 vs. 103 2 mmHg). MsrA-/- mice also exhibited decreases in spontaneous baroreex sensitivity (BRS, sequence technique) (0.9 0.1 vs. 2.2 0.1 ms/mmHg) and cardiovagal tone (HR response to cholinergic receptor blocker methylatropine = +32 5 vs. +100 17 bpm); and increases in BP variability (BPV) and sympathetic tone (HR response to beta adrenergic receptor blocker propranolol) (P \ 0.05). Ang II increased mean BP, BPV and sympathetic tone; and decreased BRS and vagal tone, with MsrA-/mice exhibiting markedly enhanced responses (P \ 0.05). Administration of the antioxidant tempol (1 mM, drinking water) reversed the Ang II-induced hypertension and autonomic dysregulation. Ang IIinfused MsrA-/- mice (n = 10) exhibited left ventricular dysfunction, increased diameter of the ascending aorta (echocardiography), and abdominal aortic aneurysms. We conclude that MsrA: (1) is required for normal BP, BRS and sympathovagal balance under basal conditions; (2) protects against Ang II-induced hypertension, autonomic dysfunction and end-organ damage; and (3) is a novel therapeutic target in hypertension. (HL14388, VA)

Prostaglandin D synthase is critical for development of chronic angiotensin II-salt hypertension in the rat
G.D. Fink, N. Asirvatham-Jeyaraj Department of Pharmacology and Toxicology, Michigan State University, East Lansing, MI, USA Chronic infusion of angiotensin II (150 ng/kg/min, sc) into rats ingesting a high salt diet (4.0 % NaCl) produces sustained hypertension (AngII-salt HT) caused in part by increased splanchnic sympathetic nerve activity. Previous work suggests that cyclooxygenase products generated in the brain during the rst few days of exposure to angiotensin II are necessary for these effects. Analyses of eicosanoid pathway gene expression in the brain during the early phase of AngII-salt HT highlighted lipocalin-type prostaglandin D synthase (L-PGDS) as a possible critical element in the response. To test that idea we continuously administered the highly selective L-PGDS inhibitor AT-56 into the brain of rats via intracerebroventricular (icv) infusion (6.6 lmol/h). We then induced our standard 14-day model of AngII-salt HT starting 5 days after icv AT-56 administration had begun. Rats receiving only icv vehicle served as controls. Blood pressure was measured continuously throughout the experiment by radiotelemetry. Sympathetic control of blood pressure was estimated from the depressor response to acute ganglion blockade with hexamethonium (30 mg/kg, ip). Control rats showed typical elevations in blood pressure during AngII infusion and a signicantly enhanced depressor response to ganglion blockade on day 8 after starting AngII. Rats receiving icv AT-56 exhibited no change in basal blood pressure but had a markedly and signicantly reduced blood pressure and sympathetic response to AngII infusion compared to control rats. Systemic administration of AT-56 via continuous subcutaneous infusion (6.6 lmol/h) also completely prevented the increases in blood pressure and sympathetic pressor activity normally

Baroreex induced changes in stressed blood volume, not cardiac output curve, is the central mechanism preventing volume load induced pulmonary edema
T. Sakamoto, T. Kakino, K. Sunagawa Department of Cardiovascular Medicine, Kyushu University, Fukuoka, Japan Background: We previously demonstrated that baroreex failure predisposes volume induced pulmonary edema. Since the baroreex changes both cardiac and vascular properties, how exactly the

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222 observed during AngII infusion. These studies reveal that L-PGDS, likely in the brain, is a necessary component of AngII-salt HT and sympathoexcitation. Since systemic inammation, sleep deprivation and obesity are all associated with increased brain levels of prostaglandin D and sympathoexcitation, our results may have broad implications for understanding neurogenic forms of hypertension.

Clin Auton Res (2012) 22:207258 well as cardiac arrhythmia is relatively uncommon compared to larger animals or humans, since high quality continuous long term ECG and arterial blood pressure (APB) recordings as well as the techniques for analysis of heart rate (HR), heart rate variability (HRV) and arrhythmia detection in the mouse present technical and computational challenges. Methods: We present data from several studies involving murine ECG and ABP signals from implanted wireless radiofrequency transmitters. We describe and compare different methods of digital signal processing, heart beat and arrhythmia detection and classication, computation of baroreex sensitivity, time domain and frequency domain HRV parameters, construction of composite plots for dynamics of HR and HRV data over time during interventional studies from an aspect specic to the mouse model. We illustrate technical challenges, common mistakes and solutions throughout the process from telemetry to the analysis results presentation. Results: During a decade of experience with murine ECG signal analysis, we have developed a toolbox of techniques specically tailored to the mouse model. Here we demonstrate the technical requirements for signal quality and processing, how wavelet based visualizations and spectrograms can signicantly aid in the characterization of dynamic changes and the detection of anomalies and artifacts and how specic plotting techniques can reveal unexpected ndings such as multiple transient atrial pacemakers during carbachol challenge experiments. We show the use of machine learning algorithms for the automatic detection and reliable subclassication of ventricular tachycardia and premature contractions after myocardial infarction with pattern recognition techniques such as articial neural networks in large data sets from long term ECG signals. Finally, we show that parallel processing and general-purpose computing on graphics processing units allow for accelerated analysis of continuous mouse ECG recordings over days with millions of heart beats as well as for providing near real-time computation of advanced analysis output during experiments.

The central chemoreex activation induces sympathoexcitation and resets the arterial baroreex without compromising its pressure stabilizing function
K. Saku, K. Sunagawa Department of Cardiovascular Medicine, Kyushu University, Fukuoka, Japan Background: The augmented chemoreex and impaired baroreex in heart failure result in excessive sympathoexcitation and poor prognosis. However, how the chemoreex interacts with the baroreex remains unknown. The purpose of this investigation was to examine the impact of chemoreex on the baroreex function under the openloop condition. Methods and Results: In 7 vagotomized rats, we vascularily isolated the bilateral carotid sinuses, controlled carotid sinus pressure (CSP) and measured SNA at the celiac ganglia and arterial pressure (AP). We activated the central chemoreex by hypercapnia (inhalation of 3 % CO2). Under the open baroreex loop, we compared the changes in AP and SNA in response to CSP with/without hypercapnia. Increasing CSP stepwise from 60 to 170 mmHg sigmoidally suppressed SNA, whereas the SNA suppression linearly decreased AP. Hypercapnia markedly increased SNA (DSNA = 53.4 7.1 %, p \ 0.01) irrespective of CSP indicating the resetting of the CSP SNA relationship (the neural arc). Hypercapnia increased the setpoint pressure (168.6 8.2 vs. 188.3 8.1 mmHg, p \ 0.01) of neural arc, whereas did not alter the SNAAP relationship (peripheral arc). The total loop gain from CSP to AP at the operating point remained unchanged (-1.09 0.13 vs. -1.43 0.18, p = ns). Random perturbation of CSP with binary white noise sequences indicated that hypercapnia did not affect the transfer functions of the neural or peripheral arcs. Therefore, the chemoreex activation did not impact on the baroreex dynamic characteristics of pressure stabilizing function. Conclusion: Hypercapnia resets the baroreex neural arc upward and increases arterial pressure, while does not affect baroreex pressure stabilizing characteristics. We conclude that the central chemoreex modies hemodynamics via sympathoexcitation without compromising baroreex function. The augmented chemoreex in heart failure cannot be responsible for the baroreex dysfunction. How chemoreex induced changes in hemodynamics contribute to CO2 homeostasis remains to be seen.

Streeten Lecture The ups and downs of blood pressure & baroreex sensitivitya historical and personal perspective
Mark W. Chapleau, Ph.D. University of Iowa and Veterans Affairs Medical Center, Iowa City, IA, USA The baroreceptor reex is a powerful regulator of blood pressure (BP). Increases and decreases in BP are buffered by baroreexmediated autonomic and circulatory adjustments. By minimizing BP variability, the baroreex protects against ischemia, syncope and endorgan damage (e.g., vascular and cardiac hypertrophy, renal failure, stroke). The baroreex also favorably inuences cardiac sympathovagal balance, and consequently affects the electrical properties of the heart. Decreased baroreex sensitivity (BRS) for control of heart rate (HR) predicts future arrhythmias and decreased survival in patients with myocardial infarction, heart failure and diabetes; increased BRS is protective. In my presentation, I will review experimental approaches and key discoveries related to the physiology and pathophysiology of the baroreceptor reex, with emphasis on studies leading up to and including work in my laboratory. Results obtained using a variety of approaches will be presented including recordings of baroreceptor afferent and sympathetic efferent nerve activity; telemetry-based measurements of cardiovascular and derived autonomic indices in conscious, genetically modied mice; electrophysiological and imaging studies of isolated baroreceptor neurons in

Advanced techniques and pitfalls of autonomic function assessment and arrhythmia analysis in the mouse model
C.M. Welzig1, J.B. Galper2 1 Department of Neurosciences, Medical University of South Carolina, Charleston, SC, USA; 2Molecular Cardiology Research Institute, Tufts Medical Center, Boston, MA, USA Background: Mice are very frequently employed as a mammalian research model and are used in a wide spectrum of experimental protocols. However, the study of autonomic function and disorders as

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Clin Auton Res (2012) 22:207258 culture; and viral vector-mediated gene transfer. Topics to be discussed include: (1) Ion channels determining the mechanosensitivity and excitability of baroreceptor afferents; (2) Modulation of afferent BRS by autocrine/paracrine factors; (3) Sensory and central mechanisms mediating adaptation and resetting of the baroreex in hypertension; (4) Mechanisms of dysautonomia in mouse models of disease and aging; and (5) Future directions for research. (NIH HL14388, US Dept Vet Aff, AHA)

223 was intact [16 5 AF-HT vs. 11 4 AF-NT vs. 7 1 pg/mL healthy; p = 0.29], and plasma prorenin was selectively elevated in hypertensive AF patients [2.0 0.5 AF-HT vs. 0.7 0.1 AF-NT vs. 0.6 0.1 ng/mL healthy; p \ 0.05]. While levels of Ang I were similar among groups, Ang II was paradoxically elevated [39 4 AF-HT vs. 42 6 AF-NT vs. 27 4 pg/mL healthy; p \ 0.05] in AF. In contrast, Ang-(17) was suppressed in AF patients [7 1 AFHT vs. 4 1 AF-NT vs. 22 6 pg/mL healthy; p \ 0.05]. The Ang II AT1 receptor antagonist losartan [50 mg, PO] signicantly reduced supine systolic blood pressure [25 15 mmHg at 6 h after administration; p \ 0.05] in 9 AF-HT patients. These ndings suggest an imbalance in Ang II and Ang-(17) activity in AF independent of hypertensive status. The source of Ang II in the absence of plasma renin activity is still under investigation. The loss of renin activity is not due to reduced renin content but may result from low substrate availability or defective enzyme activation. Prorenin levels are elevated in hypertensive AF patients, which could stimulate Ang II generation and actions. Regardless, Ang II appears to contribute to the supine hypertension of AF. Collectively, these patients offer a unique model to study cardiovascular regulation and Ang II production in the absence of autonomic and traditional renin inuences.

Blunted osmopressor response in familial dysautonomia

N. Goulding, L. Norcliffe-Kaufmann, J. Martinez, D. Roncevic, L. Stok, F. Axelrod, H. Kaufmann Dysautonomia Center, New York University School of Medicine, New York, NY, USA Drinking pure water markedly increases blood pressure in patients with chronic autonomic failure because water-induced hypo-osmolarity, sensed by peripheral osmoreceptors, triggers sympatho-excitation likely arising from a spinal mechanism. Osmosensory transduction involves transient receptor potential vanilloid 4 channels (TRPV4) expressed on afferent neurons with their cell bodies in the dorsal root ganglia (DRG). Patients with familial dysautonomia (FD, hereditary sensory and autonomic neuropathy type-III) have a reduced number of afferent neurons in the DRG. The aim of our study was to investigate whether a pronounced osmopressor response was also present in patients with FD. Nine patients with FD and 6 with chronic autonomic failure participated in this study (5 with MSA and 1 with PAF). Beat-to-beat BP was recorded in a supine position before and following the ingestion of 500 ml of room temperature water for 30 min. As expected, in patients with autonomic failure, mean blood pressure (MBP) increased signicantly after water ingestion (from 104 13 to 128 20 mmHg, p \ 0.05, max response D19 9 mmHg, p \ 0.01). In contrast, in patients with FD, water ingestion did not increase MBP signicantly over the 30 min period (90 13 to 94 13 mmHg, NS, max response D7 11 mmHg, NS,). Thus, the response to water drinking differed signicantly between the two groups (2-way ANOVA: p \ 0.0001). These ndings suggest an absence of functional peripheral osmoreceptors in FD patients and may have therapeutic implications.

Chronic effects of aliskiren versus hydrochlorothiazide on sympathetic neural responses to head-up tilt in hypertensive seniors
Y. Okada1,2, S.S. Jarvis1,2, S.A. Best1,2, T.B. Bivens1, R.L. Meier1, B.D. Levine1,2, Q. Fu1,2 1 Institute for Exercise and Environmental Medicine, Texas Health Presbyterian Hospital Dallas, TX, USA; 2UT Southwestern Medical Center, Dallas, TX, USA The cardiovascular risk remains high in hypertensives even with adequate blood pressure (BP) control. One possible mechanism may be persistent sympathetic activation via the baroreex. We tested the hypothesis that a direct renin inhibitor, aliskiren, would reduce BP without sympathetic activation, contrary to a diuretic, hydrochlorothiazide (HCTZ), in elderly hypertensives. Twelve hypertensives [stage I hypertension, 64 1 (SE) years] were treated either with aliskiren (n = 7, 300 mg daily) or HCTZ (n = 5, 25 mg daily) for 6 months. Muscle sympathetic nerve activity (MSNA), BP, heart rate (HR) and cardiac output (Qc) were measured supine and during a graded head-up tilt (HUT; 5-min 30 and 20-min 60) before and after treatment. Plasma norepinephrine and aldosterone were also assessed. Both groups had similar reductions in 24 h ambulatory BP after treatment (aliskiren: 128 3/72 2 post vs. 143 4/78 3 mmHg pre; HCTZ: 128 3/ 74 1 vs. 144 3/81 2 mmHg; all p \ 0.01). HR increased and Qc decreased during HUT in both groups with no change after treatment. MSNA was greater supine and during HUT after HCTZ treatment (supine, 75 11 post vs. 63 6 pre; 60 HUT, 86 6 vs. 78 6 bursts/100 beats; p = 0.02 for treatment). Conversely, after aliskiren treatment, supine MSNA remained unchanged, but upright MSNA was lower (supine, 69 13 vs. 64 8; 60 HUT, 75 11 vs. 82 11 bursts/100 beats; p = 0.01 for interaction of treatment 9 posture). Plasma norepinephrine concentration and aldosterone level during HUT were greater after HCTZ treatment (60 HUT; 844 225 vs. 638 175 pg/ml, p = 0.04 and 18.0 3.5 vs. 9.2 3.1 ng/dl, p = 0.02), but were unchanged after aliskiren treatment. Thus, aliskiren effectively lowered BP and reduced upright MSNA in elderly hypertensives. HCTZ evoked sympathetic activation and enhanced the reninangiotensin-aldosterone system during orthostasis.

Paradox elevations in angiotensin II, independent of plasma renin activity, contribute to the supine hypertension of primary autonomic failure
A.C. Arnold, L.E Okamoto, C. Shibao, A. Gamboa, S.R. Raj, D. Robertson, I. Biaggioni Division of Clinical Pharmacology, Vanderbilt University School of Medicine, Nashville, TN, USA At least 50 % of primary autonomic failure [AF] patients exhibit supine hypertension, despite profound impairments in sympathetic activity. Plasma renin activity is often undetectable in AF suggesting renin mechanisms are not involved. However, since aldosterone levels are preserved, we examined the status and contribution of the reninangiotensin [Ang] system in AF. Supine plasma Ang peptides were measured in hypertensive AF patients [AF-HT, n = 18], normotensive patients [AF-NT, n = 11] and matched healthy subjects [n = 10]. Despite suppressed renin activity, total renin concentration

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Clin Auton Res (2012) 22:207258 nervous system using ganglionic blockade, is associated with basal sympathetic tone. Nine healthy young women (24 3 years) and ten healthy older women (61 7 years) participated in this study. Heart rate, arterial pressure, and pulse wave velocity (PWV) were monitored before and during ganglionic blockade with trimethaphan. MSNA measured during quiet rest was greater in older women when expressed as both burst incidence (54 6 vs. 23 3 bursts/100 hb; p \ 0.01) and burst frequency (32 3 vs. 14 2 bursts/min; p \ 0.01). Aortic PWV was also higher in older women (9.0 0.6 vs. 6.4 0.3 m/s; p \ 0.01) at baseline and during ganglionic blockade (7.6 0.4 vs. 6.5 0.2 m/s; p \ 0.05). MSNA burst incidence and burst frequency were positively associated with baseline aortic PWV (r = 0.55, p \ 0.05; r = 0.63, p \ 0.01, respectively), but not peripheral PWV. Aortic PWV values during ganglionic blockade were not associated with baseline MSNA (BI: r = 0.38, p = 0.10; BF: r = 0.40, p = 0.09); however the change in aortic PWV after ganglionic blockade was inversely associated with MSNA (BI: r = -0.54, p \ 0.05; BF: r = -0.61, p \ 0.01). Taken together, these data suggest that increased sympathetic nerve activity may contribute to the development of arterial stiffness.

Association between cerebral autoregulation and white matter hyperintensities in elderly individuals
S. Purkayastha1, B. Paccha1, I. Iloputaife1, D.K. Kiely1, F.A. Sorond2, L.A. Lipsitz1 1 Institute for Aging Research, Hebrew SeniorLife, Roslindale, MA, USA; 2Neurology, Brigham and Womens Hospital, Boston, MA, USA Aim: Cerebral autoregulation (CA) maintains a relatively constant cerebral blood ow despite changes in perfusion pressure. Abnormalities in CA may threaten cerebral perfusion and result in ischemic damage to watershed regions in the periventricular white matter. Cerebral white matter hyperintensities (WMH) are prevalent among elderly people and are associated with chronic cerebral hypoperfusion and ischemic injury. The purpose of the study was to examine the association between CA and total cerebral WMH volume in elderly individuals. Methods: Thirty-seven subjects (79 6 years) from the MOBILIZE Boston study were recruited for assessment of total cerebral WMH using magnetic resonance imaging (MRI). Subjects were divided at median into low (N = 18) and high (N = 19) WMH groups based on total cerebral WMH obtained from the MRI images. Beat-to-beat blood pressure and middle cerebral artery blood velocity (MCAV) measurements were obtained from nger plethysmography and transcranial Doppler ultrasonography while subjects were seated upright for 5 min. Transfer function analyses of beat-to-beat MCAV and blood pressure variability were evaluated to determine CA. Lower transfer function gains between blood pressure and MCAV in the low frequency range (0.070.20 Hz) are considered better CA. Results: The variability in MCAV at low frequency was greater in the high compared to the low WMH group (2.39 0.6 vs. 1.02 0.2, P = 0.04) despite no differences in blood pressure variability between the two groups. Low frequency transfer function gain was also signicantly greater in the high compared to the low WMH group (0.88 0.08 vs. 0.64 0.05, P = 0.04). Conclusion: Our results suggest that a high total cerebral WMH burden is associated with impairment in CA in elderly individuals. Abnormal CA may predispose older people to cerebral hypoperfusion and ischemic damage to white matter in the brain.

Friday, November 2, 2012 Oral Presentations Plenary Lecture The autonomic responses to pregnancy
Qi Fu, M.D., Ph.D. Institute for Exercise and Environmental Medicine, Texas Health Presbyterian Hospital Dallas, and UT Southwestern Medical Center, Dallas, TX, USA In humans, pregnancy is associated with dramatic changes in maternal hemodynamics. These changes are detectable by 4 weeks of gestation,1,2 and reach a plateau in the second trimester of pregnancy.36 It has been proposed that hemodynamic changes during pregnancy occur through autonomic control mechanisms,7 but the actual role of the sympathetic nervous system in normal pregnancy as well as in hypertensive disorders of pregnancy is poorly understood. With the microneurographic technique, Greenwood et al8,9 found that muscle sympathetic nerve activity (MSNA) increased in normotensive pregnant women and was even greater in women with gestational hypertension and preeclampsia during the third trimester. They thereby concluded that sympathetic hyperactivity during the latter months of normal pregnancy helped to return the arterial pressure to non-pregnant levels, but when the increase in sympathetic activity was excessive, hypertension ensued. This notion was supported by the ndings of Schobel et al10 and Fischer et al11 showing that preeclampsia was in a state of sympathetic overactivity, which normalized after delivery. The key question that must be addressed then is whether sympathetic overactivity develops early during pregnancy, remaining high throughout gestation, or whether this sympathetic activation only occurs at term, providing the substrate for preeclampsia and other pregnancy associated cardiovascular complications. Recent work from our laboratory showed that resting MSNA increased markedly during early pregnancy (i.e., B8 weeks of gestation), remained elevated throughout the entire gestation, and was suppressed shortly after delivery in healthy normotensive women. These results suggest that sympathetic activation is a common phenomenon during pregnancy in humans. Conversely, total peripheral

The change in arterial stiffness during ganglionic blockade is associated with sympathetic nerve activity in women
J.N. Barnes1, R.E. Harvey1, E.C. Hart2, N. Charkoudian3, T.B. Curry1, J.H. Eisenach1, W.T. Nicholson1, M.J. Joyner1, D.P. Casey1,4 1 Department of Anesthesiology, Mayo Clinic, Rochester, MN, USA; 2 School of Physiology and Pharmacology, University of Bristol, Bristol, England, UK; 3Thermal and Mountain Medicine Division, U.S. Army Research Institute of Environmental Medicine, Natick, MA, USA; 4Department of Physiology and Biomedical Engineering, Mayo Clinic, Rochester, MN, USA Arterial stiffness is an independent risk factor for hypertension. Sympathetic overactivity may contribute to the age-related increase in arterial stiffness. Previously, it has been shown that arterial stiffness is associated with muscle sympathetic nerve activity (MSNA) in men. However, this has not been investigated in women. Accordingly, our purpose was to examine the association between arterial stiffness and MSNA in women. Furthermore, we sought to determine if the change in arterial stiffness, after eliminating the inuence of the autonomic

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Clin Auton Res (2012) 22:207258 resistance was lower during pregnancy compared to non-pregnancy, indicating blunted sympathetic vasoconstriction. We also found that race may affect sympathetic neural control during pregnancy. For example, Asian women had a much less prominent sympathetic activation to the skeletal muscle and the heart, but a greater activation of the renin-aldosterone system during pregnancy compared to White women. On the other hand, MSNA appeared to be comparable between Black and White pregnant women, but Blacks had greater sympathetic activation to the heart and the kidney early on during pregnancy. These different responses may contribute importantly to racial differences in the prevalence of gestational hypertension and preeclampsia in humans. Overactivation of the sympathetic nervous system can lead to an impairment of vasodilatation by a-adrenergic mechanisms.12,13 Thus, sympathetic overactivity may be a key factor in the development of hypertensive disorders during pregnancy. Indeed, we found some early signs of excessive sympathetic overactivity in one woman with gestational hypertension during the rst trimester. If these preliminary observations can be conrmed in more women with hypertensive pregnancies, it would provide invaluable information regarding the pathophysiology of gestational hypertension and preeclampsia. With this knowledge, early prevention or treatment targeted to the appropriate pathophysiology may be initiated, which may reduce maternal and fetal death or morbidity, as well as cardiovascular risks in women later in life. References: 1. Phippard AF, et al., J Hypertens. 1986;4(6):773779. 2. Chapman AB, et al., Am J Physiol. 1997;273(5 Pt 2):F777782. 3. Robson SC, et al., Am J Physiol. 1989;256(4 Pt 2):H10601065. 4. Capeless EL, Clapp JF. Am J Obstet Gynecol. 1989;161(6 Pt 1):14491453. 5. Clapp JF, 3rd, Capeless E. Am J Cardiol. 1997;80(11): 14691473. 6. Duvekot JJ, et al., Am J Obstet Gynecol. 1993;169(6): 13821392. 7. Ekholm EM, et al., Clin Auton Res. 1994;4(4):161165. 8. Greenwood JP, et al., Circulation. 2001;104(18):22002204. 9. Greenwood JP, et al., J Hypertens. 1998;16(5):617624. 10. Schobel HP, et al., N Engl J Med. 1996;335(20):14801485. 11. Fischer T, et al., Eur J Clin Invest. 2004;34(6):443448. 12. Hijmering ML, et al., J Am Coll Cardiol. 2002;39(4):683688. 13. Sverrisdottir YB, et al., PLoS One.2010;5(2):e9257.

225 Materials and methods: We studied 12 not preselected patients with difcult to control arterial hypertension (ages 4574 years) who had been admitted for renal nerve ablation. All patients were on C3 antihypertensive medications at full doses, including a diuretic. ECG, respiration, brachial and nger arterial blood pressure, and muscle sympathetic nerve activity (MSNA) were recorded before and 36 months after renal nerve ablation. Heart rate- (HRV) and blood pressure variability (BPV) were analyzed in the time and frequency domain. Pharmacological baroreex slopes were determined using the modied Oxford-bolus technique. Spontaneous sympathetic baroreex sensitivity was analyzed by the Kienbaum method. Results: Resting heart rate (pre: 61 9, post 58 8 bpm; p = 0.66) and supine blood pressure (pre: 157 20/85 12 mmHg; post: 157 20/84 12 mmHg; p = 1.0) were similar on both study days. Resting MSNA was similar before and after renal nerve ablation (pre: 34 8, post: 31 10 bursts/min; p = 0.50). In one case, blood pressure reduction of 66/30 mm Hg was not associated with a reduction in MSNA (40 vs. 41 bursts/min). Renal nerve ablation had no inuence on HRV and BPV. Baroreex mediated heart rate control and baroreex mediated control of sympathetic nerve trafc (pre: -4.8 4, post: -4.6 3 %/mm Hg; p = 0.7) did not change. Conclusion: Our data suggest that reduction in centrally generated sympathetic activity may be the exception rather than the rule following renal nerve ablation in unselected patients with difcult to control arterial hypertension. The large proportion of non responders in terms of blood pressure reduction is a matter of concern.

Methodological considerations for assessing resting spontaneous baroreex control of muscle sympathetic nerve activity in humans
S.W. Holwerda1, H. Yang2, J.R. Carter2, P.J. Fadel1 1 Department of Medical Pharmacology & Physiology, Dalton Cardiovascular Research Center, University of Missouri, Columbia, MO, USA; 2Department of Kinesiology and Integrative Physiology, Michigan Technological University, Houghton, MI, USA Spontaneous measurements for the estimation of baroreex control of muscle sympathetic nerve activity (MSNA) are increasingly being used to assess sympathetic baroreex sensitivity at rest primarily due to the relative ease of relating spontaneously occurring changes in MSNA and diastolic blood pressure (DBP). However, a thorough examination of this methodology for assessing spontaneous baroreex sensitivity in humans under resting conditions has not been performed. Indeed, although spontaneous measurements have been shown to correlate with MSNA baroreex sensitivity derived using the modied Oxford, the impact of bin size, baseline time duration, diastolic blood pressure range, and MSNA burst frequency remain unknown. This becomes important because published results have not used standard analyses methods. Thus, to comprehensively examine the inuence of varying analyses procedures on estimates of spontaneous MSNA baroreex sensitivity, weighted linear regression analysis between MSNA and DBP was performed in 100 subjects. First, intra-class correlation coefcients for varying bin sizes (1, 2, and 3 mmHg) and segment durations (1, 2, 5, and 10 min) were calculated to examine reliability of spontaneous MSNA baroreex sensitivity. Next, the inuence of the DBP range and MSNA burst frequency on the validity of the relationship between MSNA and DBP were considered. Interestingly, despite similar burst incidence MSNA baroreex sensitivity across all bin sizes, the reliability was weak for 2- and 1-min baseline durations. The diminished reliability appeared to be due to a signicant reduction in the DBP range across baseline time durations (e.g., 10 min, 25 1 vs. 1 min, 15 1 mmHg;

Catheter based renal nerve ablation does not elicit a central sympatholytic response in difcult to control hypertensive patients
J. Brinkmann1, K. Heusser1, B.M. Schmidt2, J. Menne2, G. Klein3, H. Haller2, A. Diedrich4, J. Jordan1, J. Tank1 1 Institute of Clinical Pharmacology, Hanover Medical School, Hanover, Germany; 2Division of Nephrology and Hypertension, Department of Medicine, Hanover Medical School, Hanover, Germany; 3Department of Electrophysiology, Division of Cardiovascular Medicine, Hanover Medical School, Hanover, Germany; 4Vanderbilt Autonomic Dysfunction Center, Division of Clinical Pharmacology, Nashville, TN, USA Background. Endovascular renal nerve ablation has been developed to treat resistant hypertension. Renal denervation may attenuate central sympathetic outow through decreased renal afferent nerve trafc as evidenced by a recently published case report. We tested the hypothesis that renal nerve ablation is accompanied by reduced central sympathetic nerve trafc in a larger sample.

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226 P \ 0.001); whereas MSNA burst frequency was similar across baseline time durations (P = 0.949). Overall, these ndings question the validity of using baseline period durations \5 min for assessing resting spontaneous MSNA baroreex sensitivity; an effect that appears to be related, in part, to smaller DBP ranges with shorter baseline periods.

Clin Auton Res (2012) 22:207258 diabetes. Here, we study the inducibility of ventricular tachycardia (VT) in the Akita mice by programmed ventricular electrical stimulation and investigate the ionic and cellular mechanism of arrhythmogenesis. Methods: Programmed ventricular electrical stimulation was performed in Akita and wild type (WT) mice. Left ventricular myocytes were isolated for electrophysiology and calcium imaging studies. Voltage and current clamp were used to record Ca2+ currents and action potentials. Sarcomere shortening and Ca2+ transient were measured using the Ionoptix system. Ca2+ sparks were recorded by confocal microscopy. Results: Inducibility of VT in Akita mice was signicantly increased (78.6 %, 11 of 14) compared to WT (28.6 %, 4/14, p = 0.006). Action potential duration at 90 % repolarization at 1 Hz was prolonged in Akita myocytes (61.5.1 7.7 ms, n = 7) versus WT (30.5 1.3 ms, n = 7, p \ 0.05). We determined whether these effects were associated with abnormalities of Ca homeostasis. L type Ca2+ current densities were unchanged compared to WT. However, Ca2+ transient decay time was increased in Akita (170.9 10.3 ms, n = 23) vs WT (138.6 7.3 ms, n = 20, p \ 0.05) while SERCA2a expression was decreased in the Akita heart. Furthermore, frequency of Ca2+ sparks was signicantly increased compared to WT (0.266 0.022, n = 36 vs. 0.043 0.003 sparks/lm/s, n = 13, p \ 0.001) consistent with increased Ca2+ leak. Consequently, cystolic Ca2+ concentration was signicantly elevated in Akita myocytes, leading to the occurrence of early and delayed after depolarizations which predispose to arrhythmia. Conclusions: The type 1 diabetic Akita mouse demonstrated a high level of inducibility of VT which may be due to prolongation of APD and abnormalities of Ca2+ handling.

Sleep deprivation augments cardiovascular reactivity to acute stress in humans

H. Yang1, J.J. Durocher1, R.A. Larson1, J.P. DellaValla2, J.R. Carter1 1 Department of Kinesiology and Integrative Physiology, Michigan Technological University, Houghton, MI, USA; 2Center for Sleep Medicine, Androscoggin Valley Hospital, Berlin, NH, USA Exaggerated cardiovascular reactivity to mental stress (MS) and cold pressor test (CPT) have been linked to increased risk of cardiovascular disease. Recent epidemiological studies identify sleep deprivation as an important risk factor for hypertension, yet the relations between sleep deprivation and cardiovascular reactivity remain equivocal. We hypothesized that 24 h total sleep deprivation (TSD) would augment cardiovascular reactivity to MS and CPT, and blunt MS-induced forearm vasodilation. Because associations between sleep deprivation and hypertension have been reported to be stronger in women, a secondary aim was to probe for sex differences. Mean arterial pressure (MAP) and heart rate (HR) were recorded during a 5 min MS trial and 2 min CPT trial in 28 young healthy subjects (14 men and 14 women) after normal sleep (NS) and TSD (randomized, crossover design). Forearm vascular conductance (FVC) was determined for the MS trial. MS increased MAP, HR, and FVC during both NS and TSD (p \ 0.001). HR reactivity during the nal 3 min of MS was augmented with TSD (D17 2 vs. D14 1 beats/min; p \ 0.05), and these augmented HR responses persisted during the 5 min recovery (D4 1 vs. D1 1 beats/min; p \ 0.01). Increases in MAP and FVC during MS were not different between NS and TSD. Similar to the MS trial, CPT increased MAP and HR during both NS and TSD (p \ 0.001), but only HR reactivity was augmented during TSD (D12 2 vs. D9 1 beats/min; p \ 0.05). The augmented HR persisted during the CPT recovery (D1 1 vs. D-1 1 beats/min; p \ 0.05). When analyzed for sex differences, cardiovascular responses to MS and CPT were not different between sexes or conditions (condition 9 time 9 sex, p [ 0.05). We conclude that TSD potentiates HR reactivity during and after both MS and CPT. These ndings provide new mechanistic insight regarding emerging links between sleep deprivation, stress, and cardiovascular risk.

Sympathetic hyper-responsiveness in takotsubo cardiomyopathy

L. Norcliffe-Kaufmann, J. Martinez, H. Kaufmann, H. Reynolds New York University Dysautonomia Center, New York, NY, USA Takotsubo cardiomyopathy primarily strikes post-menopausal women after an emotional shock or intense physical stress. Both stimuli trigger a powerful increase in sympathetic outow and the release of norepinephrine, which is unusually high during an episode, suggesting a hyperadrenergic mechanism for the disorder. The role of the baroreex in predisposing to takotsubo cardiomyopathy is uncertain. We studied 10 women who had a past episode of takotsubo cardiomyopathy and 10 age/BMI matched healthy women. Blood pressure and RR intervals were measured continuously and plasma catecholamines were sampled through an indwelling venous catheter. Sympathetic activation was provoked by hemodynamic (Valsalva), cognitive (stroop test) and emotional (event recall) stimuli. Parasympathetic function was assessed during slow paced breathing (E:I ratio). Baroreex sensitivity was measured using spectral and sequence techniques. Participants also underwent 24 h ambulatory blood pressure monitoring. Sympathetic responsiveness to hemodynamic, cognitive and emotional stimuli was exaggerated in the women with history of takotsubo compared to controls: Phase IV overshoot in BP after the release of the Valsalva strain was both amplied (DSBP: +31 6 vs. +10 4 mmHg, p \ 0.01) and prolonged (duration: 25 4 vs. 11 1 s); stroop test produced a greater increase in SBP (DSBP 40 6 vs. 28 3 mmHg, p \ 0.05). Compared to cognitive arousal, recalling the event that triggered their episode evoked an even greater pressor response in takotsubo women (+D 62 8 mmHg, p \ 0.04). Heart rate uctuations with paced breathing were signicantly lower in the takotsubo women (E:I ratio

Susceptibility to inducible ventricular arrhythmia in type I diabetic Akita mice is dependent on abnormalities of Ca2+ handling
H. Jin, M. Rajab, M. Aronovitz, B. Wang, K. Picard, H. Park, M. Link, J. B Galper Tufts Medical Center, MCRI, Tufts University, Boston, MA, USA Introduction: Diabetes mellitus is associated with increased risk of sudden cardiac death. Little evidence exists to support specic mechanisms to account for this association. Furthermore, there is no animal model which demonstrates arrhythmogenesis in the Type I diabetic heart. The Akita mouse has been shown to be a useful model for the study of the pathogenesis of secondary effects of type I

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Clin Auton Res (2012) 22:207258 1.15 vs. 1.42, p \ 0.01). Spectral and sequence analysis showed that baroreex gain was signicantly lower than normal. Women with takotsubo had higher peak SBP values captured during ambulatory monitoring (156 5 vs. 128 1 mmHg, p \ 0.05). No differences in catecholamine levels were apparent. Our ndings suggest that subtle abnormalities in baroreex function leading to exaggerated sympathetic responsiveness might play a role in predisposing women to takotsubo cardiomyopathy.

227 Methods: Hemodynamics and venous catecholamines were collected from POTS patients undergoing autonomic screening (n = 153, mean age 29 1 year, 129 females), and compared to healthy controls (n = 145, age 26 1 year, 87 females) who participated in ClinicalTrials.gov: High Resolution Phenotyping in Healthy Humans which included arterial pressure and catecholamines. Dominant, additive, and recessive linear models were performed with separate analyses for each variable and SNP. Results: Consistent with prior reports, norepinephrine (NE) was increased in POTS versus controls while supine and upright (P \ 0.05) but interestingly the epinephrine levels were decreased in POTS. Within controls, Arg16 homozygotes displayed greater HR and NE levels while supine and during HUT. Gln27 homozygotes displayed greater HR while supine and during HUT. In POTS, Arg16 homozygotes had a blunted increase in HR during HUT, and the Glu27 homozygotes had a greater NE response to HUT. Taken together, there was a HR-by-genotype interaction for position 16 during HUT at min 1 (P = 0.05) and min 5 (P = 0.04). We conclude that Arg16/Gly may inversely affect HR in POTS compared to controls, and there was evidence to suggest that Gln27/Glu inuenced catecholamines within POTS during HUT. We were unable to replicate previously reported effects of genotype on blood pressure in POTS. While these ndings lend additional evidence that ADRB2 polymorphisms inuence hemodynamics and catecholamines in POTS, denitive implications for management remain undetermined.

Improvement of obesity-associated insulin resistance during autonomic blockade

A. Gamboa, L. Okamoto, A. Arnold, S. Raj, A. Diedrich, N. Abumrad, I. Biaggioni. Department of Medicine, Vanderbilt University, Nashville, TN, USA A hallmark of obesity is the development of insulin resistance. Increased secretion of insulin is an initial compensatory mechanism and is thought to contribute to sympathetic activation in an attempt to restore energy balance. We have previously shown, however, that sympathetic activity has no benecial effect on resting energy expenditure in obesity. On the contrary, we hypothesize that sympathetic activation contributes to insulin resistance providing a negative feedback loop. To test this hypothesis, we determined insulin sensitivity (hyperinsulinemic euglycemic clamp) in obese subjects (30 \ BMI \ 40 kg/m2) during intact and during pharmacologically induced autonomic blockade (trimethaphan 4 mg/min IV infusion). Blood pressure was clamped during autonomic blockade by concomitant titrated IV infusion of the NOS inhibitor L-NMMA. Eleven obese subjects (41 3.6 years, 35 0.8 kg/m2, 144 4/ 90 4 mm Hg) were studied on two separate occasions randomly assigned. Seven were found to be insulin resistance and four to be insulin sensitive (Glucose Infusion Rate, GIR [ 4.5 mg/kg/min). There were no differences in age, total fat percentage, blood pressure or muscle sympathetic activity between groups. GIR increased during autonomic blockade only among subjects with insulin resistance (2.96 0.54 to 4.03 0.67 mg/kg/min for the intact and blocked days, p = 0.018). No improvement was seen in the insulin sensitive group (6.08 0.88 to 5.99 1.34 mg/kg/min for the intact and blocked days, p = 0.5). Our results support the concept that sympathetic activation has a detrimental effect on glucose utilization in obesity, and provides the rational to explore it as a therapeutic target.

The pathophysiology of neuropathic and nonneuropathic postural tachycardia syndrome

C. Gibbons, I. Bonyhay, A. Benson, R. Freeman Department of Neurology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA Objective: To dene the clinical characteristics, fatigue severity, autonomic function and differentiating features in individuals with neuropathic and non-neuropathic POTS. Background: The postural tachycardia syndrome (POTS) is dened as an exaggerated heart rate in the upright position with orthostatic intolerance. Some patients with POTS have an underlying small ber neuropathy. Methods: Twenty-one subjects (17F) with POTS and 10 healthy control subjects (7F) had skin biopsy analysis of intra-epidermal nerve ber density (IENFD), quantitative sensory testing (QST) and autonomic testing. Subjects completed quality of life, fatigue and disability questionnaires. Subjects were divided into neuropathic and non-neuropathic POTS, dened by abnormal IENFD and/or heat and heat-pain detection thresholds. Differences in autonomic function and symptom questionnaires were analyzed by ANOVA with corrections for multiple analyses. Signicance was set at P \ 0.05. Results: POTS subjects had signicantly greater fatigue, anxiety, physical impairment, orthostatic intolerance and perceived disability than controls (P \ 0.0001 all questionnaires). Individuals with nonneuropathic POTS had greater anxiety, orthostatic intolerance and perceived disability than those with neuropathic POTS. Neuropathic POTS subjects had higher supine blood pressures (P \ 0.05), higher heart rates (P \ 0.05), lower 30:15 ratios (P \ 0.05) and lower Valsalva ratios (P \ 0.05). POTS subjects had lower IENFD at the distal leg than controls (P \ 0.05) but those with non-neuropathic POTS were similar to controls. Neuropathic POTS subjects had higher levels of distal sympathetic adrenergic innervation than those with nonneuropathic POTS or healthy control subjects. Discussion: POTS subtypes can only be distinguished by evaluation for small ber neuropathy. Patients with non-neuropathic POTS have

Beta-2 adrenergic receptor polymorphism and hemodynamics in patients with postural orthostatic tachycardia syndrome and healthy controls
M.N. Manento1, L.R. Gullixson1, K.K. Nickander2, P.A. Low2, J.H. Eisenach1 1 Department of Anesthesiology, Mayo Clinic, Rochester, MN, USA; 2 Department of Neurology, Mayo Clinic, Rochester, MN, USA Previous studies suggest that polymorphisms in the beta-2 adrenergic receptor gene (ADRB2) inuence hemodynamics in postural tachycardia syndrome (POTS). To replicate these ndings in a large cohort of POTS patients and healthy controls who underwent head-up tilt (HUT), we tested the hypothesis that two common single nucleotide polymorphisms (SNPs) in the coding region of ADRB2 (Arg16/Gly and Gln27/Glu) inuence the hemodynamic and catecholamine responses to HUT.

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228 greater anxiety, orthostatic intolerance and perceived disability despite better overall autonomic function than those with neuropathic POTS. These ndings suggest that neuropathic and non-neuropathic POTS have different pathophysiological mechanisms that underlie the postural tachycardia. These ndings have implications for therapeutic interventions to treat this disorder. Acknowledgement: Study supported by NIH NINDS K23NS050209 (CHG) and NIH RO1 HL059459 (RF).

Clin Auton Res (2012) 22:207258 present study was designed to examine the durability of this intervention in improving symptoms, functioning and psychological distress in a sample of adolescents with POTS who had failed standard intervention. Fifteen adolescents, ages 1318, diagnosed with POTS were participants in this study. The majority of patients were female (73 %) and Caucasian (100 %). All of the patients also reported chronic pain in addition to their POTS symptoms. Measures included a questionnaire that assessed POTS symptoms, the Functional Disability Index, the Center for Epidemiological Studies-Depression-Child questionnaire, and the Multidimensional Anxiety Questionnaire. Measures were completed at admission and discharge from the 3 week multidisciplinary rehabilitation program and at 3 month follow-up. Using repeated measures ANOVA analyses, patients demonstrated signicant improvements across three time points (baseline, after treatment, and 3 months followup) on measures of depression (F = 15.46, p \ 0.001), anxiety (F = 4.82, p \ 0.05), and functional disability (F = 35.71, p \ 0.001). Patients also demonstrated signicant improvements in POTS symptoms which included rapid heart rate, nausea, dizziness, blurred vision, weakness, shakiness, anxiety, pale, clammy (F = 8.63, p \ 0.01). These data suggest that the improvements initially made at the end of multidisciplinary treatment are maintained at 3 month follow-up.

Deconditioning in patients with orthostatic intolerance

A. Parsaik, T.G. Allison, W. Singer, D.M. Sletten, M.J. Joyner, E.E. Benarroch, P.A. Low, P. Sandroni Mayo Clinic, Rochester, MN, USA Objective: To study the frequency and degree of deconditioning, clinical features and the relationship between deconditioning and autonomic parameters in patients with orthostatic intolerance. Methods: We retrospectively studied all patients seen for orthostatic intolerance at Mayo Clinic between January 2006 and June 2011, who underwent both standardized autonomic and exercise testing. Results: One hundred and eighty four patients [84 Postural Orthostatic Tachycardia Syndrome (POTS), 100 without orthostatic tachycardia (OI)] fullled inclusion criteria. Eighty nine percent were females; median age was 27.5 years (IQR2237). Symptoms duration was 4 years (IQR 27.8). Ninety three percent of patients had deconditioning (reduced maximum oxygen uptake with VO2 max% \85 %) during exercise. This nding was unrelated to age, gender, and duration of illness. The prevalence of deconditioning was similar between POTS (95 %) and OI (91 %). VO2 max% had a weak correlation with a few autonomic and laboratory parameters, but adequate predictors of VO2 max% could not be identied. Conclusion: Reduced VO2 max% consistent with deconditioning is present in almost all patients with orthostatic intolerance and may play a central role in pathophysiology. This nding provides a strong rationale for retraining in the treatment of orthostatic intolerance. None of the autonomic indices are reliable predictors of deconditioning.

Objective measures of sleep in patients with POTS

S.J. Kizilbash1, P.R. Fischer1, R.M. Lloyd1,2 1 Department of Pediatrics and Adolescent Medicine, Mayo Clinic, Rochester, MN, USA; 2Center for Sleep Medicine, Division of Pulmonary and Critical Care, Mayo Clinic, Rochester, MN, USA Background: Sleep disturbance is a common symptom reported by patients with Postural Orthostatic Tachycardia Syndrome (POTS). However, there are no studies investigating the objective measures of sleep. Objective: To analyze the objective measures of sleep in patients with POTS. Method: A retrospective chart review of pediatric patients presenting to Mayo Clinic for a multidisciplinary evaluation of chronic symptoms who were diagnosed with POTS based on [30 beats/min change in heart rate during a tilt table test. They also underwent sleep evaluation with one or more objective studies of sleep; Polysomnography (PSG), Actigraphy and/or Multiple Sleep Latency Test (MSLT) between 3/2000 and 3/2012. Results: Fifty-eight patients fullled the inclusion criterion. The mean age at onset of symptoms was 12.9 years and 71 % were females. Fatigue was reported by 92 %, subjective insomnia by 54 % and hypersomnia by 40 % of patients. PSG showed increased initial sleep latency [15 min) in 47 % and increased arousal ([12/h) in 43.1 %. Increased periodic limb movement index was seen in 45.1 % (normal B5 in pediatrics) indicating periodic limb movement disorder (PLMD). There was no statistically signicant difference in the mean ferritin values of patients with and without PLMD (27.5 vs. 24.7 mcg/ L, p 0.51). Sleep architecture was relatively preserved. Mean Apnea/ Hypopnea Index was 1.9 events per hour (normal B1 in pediatrics). Actigraphy demonstrated delayed sleep phase tendencies in 88.8 % and day time napping in 77.7 %. Ten of the 17 patients who underwent actigraphy had ndings consistent with erratic sleep pattern. Of the 10 patients who underwent MSLT, 6 had evidence of central hypersomnolence including 4 with idiopathic hypersomnia and 2 with narcolepsy. Conclusion: Patients with POTS have objective evidence of primary sleep disorders including periodic limb movement disorder, circadian rhythm disturbance and central hypersomnia.

Preliminary data on the durability of improved symptoms, functioning, and psychological distress in adolescents with POTS treated in a multidisciplinary treatment program
B.K. Bruce1, T.E. Harrison2, K.E. Weiss1, P.R. Fischer3, S.P. Ahrens3, W.N. Timm4 Departments of Psychology and Psychiatry,1 Anesthesiology,2 Pediatric and Adolescent Medicine,3 and Physical Medicine and Rehabilitation,4 Mayo Clinic, Rochester, MN, USA Postural orthostatic tachycardia syndrome (POTS) can result in signicant disability and psychological distress in adolescents. Symptoms of POTS can include sweating, dizziness, shortness of breath, and presyncope which can lead to the avoidance of many activities. Often school attendance is signicantly impacted, as well as participation in sports, social activities, and family participation. In the most severe patients, POTS can result in patients who are essentially home-bound. Treatment to date has focused primarily upon pharmacological treatment. An initial study showed signicant improvement in functioning, depression, and anxiety in patients with POTS following multidisciplinary treatment. The

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Clin Auton Res (2012) 22:207258

229 relationships between glycemic variability, brain tissue and functional measures. Methods: Forty-three T2DM and twenty-six non-DM subjects aged 5085 years completed continuous glucose monitoring (CGM) for 3 days. Glycemic variability was quantied using a novel approach based on the ensemble empirical mode decomposition algorithm (EEMD). EEMD enables decomposition of the raw GCM time-series into multiple glycemic variability cycles (GVCs) linked to physiological rhythms: e.g., autonomic and hormonal (0.52 h), meal (45 h); sleep/wake (1012 h) and diurnals. Regional brain volumes were quantied from 3T MRIs. Numerous laboratory, cognitive and functional assessments were completed. Results: The DM group demonstrated greater glycemic variability than controls at multiple time-scales (GVCs: 2 h, meal, sleep/awake, diurnal, p \ 0.0001), which were correlated with higher HbA1c (p \ 0.05). In diabetics, greater GVC for sleep/wake cycle was associated with worse verbal learning scores (r2 = 0.24, p \ 0.015) and depression (r2 = 0.18, p \ 0.014). For all subjects, GVCs were associated with slower normal and dual task walking (r2 = 0.10.37, p \ 0.05). GVCs (0.52 h) were linked to lower regional gray matter volumes in learning and memory circuits, insular cortex and regions for motor and visuospatial processing, mainly in the temporal and parietal lobes (r2 = 0.260.74, p \ 0.05). GVCs (0.52 h) were linked with less blood pressure dipping at night, worse sleep efciency and atrophy of the insular cortex. Conclusions: Multi-scale GV is a promising measure of glycemic control that may be sensitive to underlying inuences associated with different physiological rhythms; e.g. hormonal modulation, cardiovascular autonomic rhythms, meal and sleep/wake cycle. In diabetics, increased GV is associated with worse cognition, more depression and brain atrophy. DM-related increases in glycemic variability associated with multiple physiological rhythms may be independent predictors of brain atrophy and functional decline.

Reduced alpha-adrenergic vascular response: the physiological link between postural orthostatic tachycardia syndrome and neurally mediated syncope
N. Mehta, M. Tavora-Mehta, J.C. Guzman, C.A. Morillo Department of Cardiology, McMaster University, Hamilton, ON, Canada Introduction: The purpose of this study was to test the hypothesis that impaired alpha (a) adrenergic vascular response may be a common pathophysiological link between Postural Orthostatic Tachycardia Syndrome (POTS) and neurally mediated syncope (NMS). Methods: Fifteen POTS and 15 NMS patients who had a positive head-up tilt test (HUT) at 70, during 15 min drug free, were compared to 15 patients with suspected NMS with a negative HUT with isoproterenol provocation (Neg-HUT). The alpha-adrenergic sensitivity (D blood pressure-phenylephrine) and activity (D blood pressure-phentolamine) and catecholamine levels in supine and at 5 and 10 min of HUT were analyzed. Cardiac hemodynamic parameters obtained from the Task Force Monitor were measured at supine and during a 15 min drug free HUT. Results: Mean a-adrenergic sensitivity was reduced in all three groups compared to healthy volunteers from literature data (Normal values: 107 38). a-adrenergic sensitivity was lower in POTS patients compared to Neg-HUT patients (32.3 28.5 vs. 54.0 33.3; p = 0.04). No differences were observed in a-adrenergic activity. Stroke index (SI) was similar between groups in supine and during HUT. Compared to Neg-HUT, POTS patients had higher norepinephrine levels at 10 min of HUT and higher heart rate delta (D) changes (from supine to HUT). Conversely, POTS had lower D changes in total peripheral resistance index (TPRI) (-163.3 773.0 vs. 230.4 825.3 vs. 644.2 542.9 dyn s m/cm5, respectively; p \ 0.05). Conclusions: Alpha receptor sensitivity was signicantly impaired in POTS patients compared to patients with a negative HUT. TPRI response to orthostatic challenge was also primarily impaired in POTS patients. Impaired a-adrenergic receptor sensitivity may share a common pathophysiological pathway in orthostatic intolerance syndromes.

The laser Doppler imaging axon-reex are areaa novel regression thresholding based technique to assess neurovascular function
T. Siepmann, B.M. Illigens, R. Freeman, C. Gibbons Department of Neurology, Carl Gustav Medical School, Dresden, Germany Background: Laser Doppler Imaging (LDI) can measure neurovascular function in patients with small ber neuropathy through assessment of the vasomotor axon-reex. However, previous studies show conicting results in patients with neuropathy, in part, because no standard LDI data analysis method has been established. This study reports the efcacy of a novel LDI image analysis technique in the detection of vasomotor C-ber function changes in a capsaicin model of small ber neuropathy. Methods: Eighteen healthy subjects ages 2127 underwent occlusive application of 0.1 % capsaicin cream on the lateral thigh over 48 h to cause local small ber nerve damage. Placebo was applied on the contralateral thigh under randomized conditions. Axon-reex mediated are was induced through iontophoresis of 10 %-acetylcholine. Post-capsaicin and placebo LDI measurements were taken from both thighs for 4 weeks on day 3, 10, 17, 24 and 31. LDI axon-reex are area assessment was performed using our regression thresholding technique and the results were compared to two previously reported LDI methods. Skin biopsies were performed to measure intra-epidermal nerve ber density (IENFD) in the capsaicin and placebo treated regions. Results: IENFD was reduced in capsaicin treated skin (2.8 2.9 bers/mm capsaicin vs. 17.4 5.7 bers/mm placebo: p \ 0.0001). The axon-reex are area as measured by our regression method was

Saturday, November 3, 2012 Oral Presentations Multi-scale glycemic variability affects brain structure and functional outcomes in type 2 diabetes mellitus
X. Cui1,2, A. Galica3, B. Manor3, A. Abduljalil4, C.-K. Peng1,5, V. Novak3 1 Division of Interdisciplinary Medicine and Biotechnology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA; 2School of Information Engineering, Wuhan University of Technology, Wuhan, Hubei, China; 3Division of Gerontology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA; 4Center for Advanced Magnetic resonance Imaging, The Ohio State University, OH, USA; 5Center for Dynamical Biomarkers and Translational Medicine, National Central University, Chungli, Taiwan Background: Diabetes mellitus (DM) increases the risk for dementia. However, complex interactions between chronic hyperglycemia and glycemic variability are not well understood. We studied the

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230 reduced on all evaluation days in capsaicin treated skin (p \ 0.05) but not in control treated skin. Our regression threshold method proved more sensitive than the two previously reported LDI methods in showing differences between capsaicin treated and control skin on all testing days (p \ 0.05) Discussion: This study demonstrates that regression thresholding based LDI measurements of the axon-reex are area can detect neurovascular dysfunction due to small nerve ber damage. This technique appears to differentiate neuropathic and non-neuropathic cutaneous regions more effectively than previously reported methods. This test may supplement the clinical assessment of small ber neuropathy

Clin Auton Res (2012) 22:207258 Introduction: Diabetes mellitus is associated with an impaired response of the heart to parasympathetic stimulation and increased cardiovascular mortality and sudden death. Decreased heart rate variability (HRV) has been shown to be a risk factor for cardiovascular disease and has been associated with sudden cardiac death in young type I diabetics, while parasympathetic stimulation has been shown to be protective against ventricular tachycardia (VT). We previously demonstrated that patients treated with pravastatin had increased parasympathetic activity and decreased ventricular ectopy. We also previously demonstrated that the Type I diabetic (Akita) mouse has a markedly decreased response to parasympathetic stimulation. Here we determine whether pravachol treatment reverses the abnormality in HRV and heart rate response to parasympathetic stimulation in Akita mice and whether this effect is associated with decreased inducibility of VT via programmed ventricular stimulation in the Akita mouse. Methods: Heart rate was determined using implantable ECG transmitters. The increase in the normalized high frequency component of HRV (HF) determined as HF fraction, was calculated over time after injection of propranolol in placebo and pravachol treated Akita mice. For programmed stimulation, an intracardiac octapolar catheter was placed in the right ventricle via the jugular vein followed by drive trains of 8 beats at 100 with up to 3 premature extrastimuli at progressively shorter cycle lengths until refractoriness. These were repeated at drive trains of 90 and 80 ms. VT was dened as C4 beats. Results: HF fraction at 15 min after propranolol was decreased in Akitas, 48.6 5.2 % versus 70.9 4.8 % in WT (n = 10, P = 0.005) and increased from 58.2 2.5 % in placebo to 68.8 3.6 % (n = 7, P = 0.033) in pravachol (10 mg/kg) treated mice. The decrease in heart rate in response to carbamylcholine was also signicantly increased in Pravachol treated mice. Akita mice were signicantly more vulnerable to stimulation of VT 78.57 % (11 of 14), compared to WT 28.57 % (4 of 14, P = 0.006). Pravastatin treated Akita mice were less vulnerable to VT 36.84 % (7 of 19), compared to placebo treated Akita mice 75 % (12 of 16, P = 0.023). Conclusion: These data support the hypothesis that statins might protect the diabetic heart from arrhythmias via an increase in HRV.

Long-term outcomes in autoimmune autonomic ganglionopathy

S. Muppidi 1, E.B. Spaeth1, C. Gibbons2, S. Vernino1 1 Department of Neurology and Neurotherapeutics, UT Southwestern Medical Center, Dallas, TX, USA; 2Department of Neurology, Beth Israel Deaconess Medical Center, Boston, MA, USA Objective: To assess the long-term outcome in patients with autoimmune autonomic ganglionopathy (AAG). Methods: We identied AAG patients from two medical centers from 2003 to present. We reviewed clinical manifestations, comprehensive autonomic evaluation, ganglionic acetylcholine receptor (gnAChR) antibody titers and immunosuppressive therapy. Some patients completed an Activities of Daily Living (ADL) questionnaire related to their autonomic dysfunction at onset and at present. Results: Thirteen patients during the study period (nine women; mean age of 54.3 years) were identied. Twelve were seropositive (gnAChR titer [0.05). Three patients had acute onset (\4 weeks), ve had subacute onset (48 weeks), and ve had chronic onset ([8 weeks). At onset, all but one patient had orthostatic hypotension and GI hypomotility. Eleven patients had decreased sweating, saliva production, and bladder urgency. All four men had erectile dysfunction. Four patients complained of limb sensory symptoms. All but one patient had severe global autonomic failure and eight had pupillary dysfunction on objective testing. Composite Autonomic Severity Score was[8/10 in eight patients. Autonomic function improved in some patients with decrease in antibody titer. For initial therapy, twelve patients received prednisone, eight received IVIG and/or plasma exchange. For maintenance immunosuppression, patients were on prednisone and either azathioprine or mycophenolate mofetil and some were on regular plasma exchange therapy. Mean duration of follow up was 6 years and during the follow up, one patient developed diffuse Large B Cell Lymphoma after treatment with mycophenolate mofetil. One patient was diagnosed with rectal adenoma carcinoma at the onset of AAG symptoms. Five patients completed a questionnaire regarding ADL, and all but had a signicant improvement. Conclusions: In our series, AAG patients responded to immunosuppressive therapy, with dramatic improvement in their ADLs and some improvement in objective measures of autonomic function. Two patients had malignancy, but the relationship to AAG is unclear.

The quantication of sudomotor nerve bers: a multicenter study in diabetes

C.H. Gibbons1, J. Lafo1, G. Smith2, R. Singleton2, R. Freeman1 1 Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA; 2University of Utah, Salt Lake City, UT, USA Background: We have recently reported techniques to quantify the sweat gland nerve ber density (SGNFD) in healthy subjects and patients with diabetes. We sought to validate these ndings against a well established cohort of healthy controls and patients with diabetes and to develop novel methods to improve collaborative efforts on the structural investigation of autonomic nerve bers. Methods: We compared the sweat gland nerve ber density (SGNFD) of a cohort of 36 patients with diabetes and 72 healthy controls studied in Boston to a group of 151 patients with diabetes and 30 healthy controls studied at the University of Utah. Tissue was reviewed from existing skin biopsies taken for evaluation of intraepidermal nerve ber density (IENFD) and stained with PGP 9.5. Every sweat gland was digitally captured by light microscopy with an in focus, and blurred image. Images were transferred digitally from Utah to Boston for analysis using automated and manual counting as previously reported (Gibbons, Muscle & Nerve 2010). Results: There were signicant differences between control sweat glands and diabetic sweat glands in the Utah group using the

Type I diabetic Akita mice demonstrate decreased heart rate variability and increased inducibility of ventricular tachycardia which are reversed by statins
C.M. Welzig1, H.-J. Park2, M. Rajab2, M. Aronovitz2, H. Jin2, M.S. Link2, J.B. Galper2 1 Department of Neurosciences, Medical University of South Carolina, SC, USA; 2Molecular Cardiology Research Institute, Tufts Medical Center, Boston, MA, USA

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Clin Auton Res (2012) 22:207258 automated SGNFD counting technique at the proximal thigh (13.4 4.9 % vs. 8.5 4.8 %, P \ 0.001), distal thigh (13.3 7.2 % vs. 9.3 7.7 %, P \ 0.05) and distal leg (12.5 7.4 % vs. 6.8 6.8 %, P \ 0.001). There were signicant differences between control sweat glands and diabetic sweat glands in the Utah group using the manual SGNFD counting technique at the proximal thigh (53.9 15.1 % vs. 33.8 9.6 %, P \ 0.001), distal thigh (48.6 17.2 % vs. 34.5 19.7 %, P \ 0.05) and distal leg (40.1 17.4 % vs. 16.8 15.5 %, P \ 0.001). There were no signicant differences in SGNFD by group (control or diabetes) or biopsy location obtained from the Utah and Boston cohorts (P = NS). Discussion: Both the automated and manual sweat gland counting methods could detect differences between groups of control subjects and individuals with diabetes. The manual counting technique more clearly discriminates individual subjects, but is more labor intensive. Our data highlight the ability to analyze SGNFD from existing skin biopsy databases and demonstrate a simple method suitable for collaborative studies via electronic transfer of images for analysis.

231 patients were headache 11 versus 0 %, dizziness 8 versus 1 %, nausea 5 versus 0 %, and fatigue 4 versus 3 %. Conclusions: Droxidopa signicantly improved symptoms and raised BP in the standing position in symptomatic NOH patients. The drug was well-tolerated and caused no serious AEs.

What is MSNA doing at the onset of syncope?

D.L. Jardine Department of General Medicine, Christchurch Hospital, Christchurch, NZ Background: The mechanism of vasovagal syncope has traditionally been thought to consist of vasodilatation (mediated by peripheral sympathetic withdrawal) and bradycardia, secondary to increased vagal activity on the heart. Recent MSNA studies have challenged not only vasodilatation as the key mechanism, but also sympathetic withdrawal. Aim: To review all recordings of tilt-induced syncope in our laboratory with satisfactory BP, HR and MSNA recordings in order to clarify the sequence of events particularly during the nal minute of presyncope. Methods: All patients selected were being investigated for symptoms of vasovagal syncope and underwent 60 head-up tilt testing with continuous monitoring of BP (intra-arterial or FINAPRES), HR and MSNA. In addition, stroke volume, cardiac output and total peripheral resistance were derived from the arterial waveform using MODELFLOW. If patients remained normotensive after 20 min of tilt, GTN spray was administered, as per tilt protocol. Results: 65 patients (mean age 46.1 2 years, 37 females) were selected from 340 tilts undertaken between January 1995 and September 2005. During presyncope, MBP fell from 101 2 to 62 2 mmHg [p \ 0.001]; HR from 82 2 to 78 3 bpm; cardiac output from 89 2 to 77 3 % baseline [p \ 0.001]; and TPR from 114 4 to 92 3 [p \ 0.001]. During the last minute, MSNA [bursts/min] fell in 56 patients [88 %], but only below baseline levels in 14 [22 %]. MSNA burst size [burst area per beat] increased in 24 [38 %]. MSNA recording elds only included recovery from syncope in 32 [50 %]. Conclusion: Measurement of MSNA during the last stages of presyncope is difcult and results may be affected by eld loss, sampling intervals and variation in the onset of hypotension and bradycardia between individuals. During the last minute of presyncope, MSNA burst frequency falls in most patients, and this is not all mediated by the bradycardia effect. Burst size is more variable and may fall later or even increase in some patients.

Treatment of neurogenic orthostatic hypotension (NOH) with droxidopa: results from a multicenter, double-blind, randomized, placebo-controlled, parallel group, induction design study
H. Kaufmann1, P. Low2, I. Biaggioni3, C.J. Mathias4, R. Freeman5, L. A. Hewitt6 1 New York University Dysautonomia Center, New York, NY, USA; 2 Mayo Clinic, Rochester, MN, USA; 3Vanderbilt University, Nashville, TN, USA; 4Imperial College London, London, UK; 5Beth Israel Deaconess Medical Center, Boston, MA, USA; 6Chelsea Therapeutics Inc., Charlotte, NC, USA Objective: Assess the clinical effect of droxidopa in subjects with symptomatic NOH. Background: Symptoms of NOH (e.g, lightheadedness, falls, and syncope) result from low blood pressure (BP) upon standing due to impaired norepinephrine release from sympathetic nerve terminals. Droxidopa, an orally active synthetic amino acid, may improve standing BP and NOH symptoms by augmenting norepinephrine levels. Methods: Multinational trial evaluated safety and efcacy of droxidopa in 263 symptomatic NOH patients. Primary efcacy variable was the Orthostatic Hypotension Questionnaire (OHQ) composite score. After an open-label droxidopa dose-optimization phase (100600 mg tid) and 7-day washout, patients were randomized in double-blind fashion to receive droxidopa or placebo for 7 days. Results: Responders (C1 point improvement on OHQ item 1 and C10 mmHg increase in standing systolic BP [SBP] during the openlabel phase) were randomized to treatment with their optimized droxidopa dose (n = 82) or placebo (n = 80). Underlying diseases and age were similar in the droxidopa and placebo groups: age 57 versus 56 years, 51 versus 53 % male, Parkinsons disease 43 versus 38 %, multiple system atrophy 17 versus 15 %, primary autonomic failure 32 versus 35 %, and nondiabetic autonomic neuropathy 3 versus 7 %, respectively, and other diagnoses 5 % in both groups. The mean change in OHQ composite score showed a statistically signicant, clinically meaningful improvement in patients taking droxidopa vs those taking placebo (-1.83 2.07 vs. -0.93 1.69, respectively, p = 0.003). Standing SBP increased 11.2 mmHg with droxidopa versus 3.9 mmHg with placebo (p \ 0.001). Supine hypertension (SBP [ 180 mmHg) occurred in 4 (5 %) droxidopatreated versus 2 (3 %) placebo-treated patients. The most frequent adverse events (AEs) in droxidopa-treated versus placebo-treated

A meta-analysis of pharmacologic treatments of orthostatic hypotension

C.H. Gibbons1, S. Raj2 1 Department of Neurology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA; 2Department of Neurology, Vanderbilt University Medical Center, Nashville, TN, USA Background: A number of pharmacologic therapies are widely utilized for the treatment of orthostatic hypotension, although the benets are not fully established. Objective: To identify and evaluate the benets and harms of all pharmacologic treatments for postural hypotension.

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232 Methods: We conducted a review of all available literature from the Cochrane central register of controlled trials, Medline (19662010) and EMBASE (19802010) using the following search terms: orthostatic hypotension, postural hypotension, orthostatic intolerance, neurally mediated hypotension and autonomic hypotension. We searched for randomized, double blind, placebo controlled trials. Our primary outcome was the change in mean systolic and or diastolic pressure in the upright position pre and post-treatment. Secondary outcomes included change in symptom scores, chronic change in upright blood pressure and adverse events due to treatment. Results: We reviewed [3,000 abstracts and identied 62 articles appropriate for review. Although several articles suggest a benet of drug treatment, none of the articles reported complete outcome data, blinding or randomization and none of the data was available from the authors of the articles. Discussion: After an exhaustive review of the literature on orthostatic hypotension, we conclude that there is insufcient data to make conclusions about the effectiveness of any pharmacologic treatments. All studies reported information in a limited and diverse fashion, with many outcome values only included in gure format. Some studies only reported diastolic, systolic or mean blood pressures, or mean change in blood pressures. We were unable to obtain actual data from any study. We conclude that the American Autonomic Society should take a lead role in dening outcomes for studies of orthostatic hypotension.

Clin Auton Res (2012) 22:207258 increase in cardiac output due to volume infusion. These data indicate that, unlike normothermia, increases in cardiac output via volume infusion do not increase cerebral perfusion in hyperthermic individuals. Therefore, the preservation of LBNP tolerance while hyperthermic, following rapid volume infusion, is not due to increases in cerebral perfusion prior to the LBNP challenge.

Patterns of diagnosis and intervention in neurogenic orthostatic hypotension (NOH): a patient-ow study
H. Kaufmann1, R.E. Paquette2 1 New York University, Dysautonomia Center, New York, NY, USA; 2 Copernicus, Boston, MA, USA Objective: To elucidate current patterns of treatment for neurogenic orthostatic hypotension (Neurogenic OH or NOH), especially roles of different specialties, factors governing treatment decisions, and interventions utilized. Methods: For this patient-ow study, 110 neurologists, 110 cardiologists, and 110 primary-care physicians (PCPs) were interviewed. All had C120 patients per month, including C8 with NOH (C10 for neurologists) in Parkinsons disease (PD), multiple system atrophy (MSA), or pure autonomic failure (PAF). Each interview included 3 chart reviews for a total of 990 unique patient charts. Results: Clinicians roles: By monthly average, neurologists were seeing the most NOH patients (48, including 35 with PD). However, substantial numbers were seen by PCPs (41, including 22 with PD and 10 with MSA) and cardiologists (37, including 16 with PD and 14 with PAF). Treatment decisions: At diagnosis, neurologists had prescribed medications for 83 % of NOH patients, cardiologists for 80 %, and PCPs for 57 %. For changing therapy, 95 % of neurologists, 91 % of cardiologists, and 74 % of PCPs considered themselves the primary decision-maker, and 67, 58, and 59 % felt somewhat to completely condent in treating NOH. However, only 5 % of NOH patients had undergone any change of therapy during the past 2 years. Interventions: Among the chart reviews, 67 % of NOH patients initially received monotherapy, 9 % received combination therapies, and 24 % received no pharmacotherapy. Among monotherapy users, 53 % took udrocortisone and 33 % midodrine. Neurologists were the most likely to prescribe monotherapy, to prescribe medication plus lifestyle modication, and to consider their patients NOH very well to extremely well controlled (52 % of neurologists cases, 48 % of cardiologists cases, and 36 % of PCPs cases). Conclusions: Although neurologists see the most NOH, especially in PD, cardiologists and PCPs have substantial numbers of patients and often act autonomously. Across specialties, physicians appear to do little to alter NOH management over time.

Increasing cardiac output does not change middle cerebral artery blood velocity in the hyperthermic human
C.G. Crandall1, T. Seifert2, T.E. Wilson3, M. Bundgaard-Nielsen2, N.H. Secher2 1 University of Texas Southwestern Medical Center and Institute for Exercise and Environmental Medicine, Texas Health Presbyterian Hospital Dallas, TX, USA; 2Risghospitalet, University of Copenhagen; 3Ohio University College of Osteopathic Medicine Hyperthermia severely compromises lower-body negative pressure (LBNP) tolerance, while tolerance in this thermal condition is preserved if preceded by rapid volume infusion (Keller et al. J Phyisol 2009). In normothermic individuals, volume infusion increases cerebral blood ow, reportedly due to increases in cardiac output (Ogoh et al. J Phyisol 2005). The present study tested the hypothesis that rapid volume infusion in hyperthermic individuals increases cerebral perfusion, which may contribute to the aforementioned preservation of LBNP tolerance. In 8 healthy male subjects (29 5 years), middle cerebral artery blood velocity (transcranial Doppler), arterial blood pressure (cannulation of radial artery), cardiac output (thermodilution), and PaCO2 (arterial blood gas) were measured while subjects were normothermic, passively heat stressed (i.e., hyperthermic), and hyperthermic after rapid infusion of 500 ml synthetic colloid plus saline (12 ml/kg total volume infused). Hyperthermia increased pulmonary artery blood temperature (36.6 0.3 to 37.7 0.3 C; P \ 0.01) and cardiac output (6.4 0.9 to 10.7 2.1 l/min; P \ 0.01), while decreasing cerebral blood velocity (59 7 to 53 12 cm/s; P \ 0.01) and mean arterial pressure (91 8 to 80 7 mmHg; P \ 0.01). Subsequent volume infusion, while remaining hyperthermic, further increased cardiac output (to 13.8 2.4 l/min; P \ 0.01 relative to normothermia and hyperthermia), without changing cerebral blood velocity (55 12 cm/s; P = 0.4) or mean arterial pressure (82 5 mmHg; P = 0.3). PaCO2 was unchanged throughout all conditions and perturbations. Thus, cerebral perfusion was unchanged despite *3 l/min

Poster Session I Poster #1 A randomized, double-blind, placebo-controlled clinical trial of Rifampicin in multiple system atrophy
P.A. Low1, S. Gilman2, D. Robertson3, I. Biaggioni3, W. Singer1, H. Kaufmann4, S. Perlman5, W. Cheshire6, S. Vernino7; R. Freeman8, R.A. Hauser9, S. Lessig10 1 Mayo Clinic, Rochester, MN, USA; 2University of Michigan, Ann Arbor, MI, USA; 3Vanderbilt University, Nashville, TN, USA; 4New York University Dysautonomia Center, New York, NY, USA;

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Clin Auton Res (2012) 22:207258

5

233
1

UCLA Medical Center, Los Angeles, CA, USA; 6Mayo Clinic, Jacksonville, FL, USA; 7University of Texas Southwestern Medical Center, Dallas, TX, USA; 8Beth Israel Deaconess Medical Center, Boston, MA, USA; 9University of South Florida, Tampa, FL, USA; 10 University of California, San Diego, San Diego, CA, USA Objective: To describe a Phase III study intended to determine whether Rifampicin slows or reverses the progression of multiple system atrophy (MSA). Background: MSA is a rapidly progressive disorder characterized by autonomic failure with parkinsonism and/or cerebellar ataxia. It is dened neuropathologically by glial cytoplasmic inclusions consisting of aggregated misfolded alpha-synuclein with widespread neuronal degeneration. In a transgenic mouse model of MSA, Rifampicin, a bactericidal antibiotic, inhibits formation of alpha-synuclein brils and disaggregates already formed brils, thereby improving behavioral abnormalities and halting or reversing neuropathological changes. Methods: We initiated a randomized, double-blind, placebo-controlled 12 months clinical safety/efcacy study of 100 pts with possible or probable MSA, 50 % consigned to active drug (Rifampicin 300 mg twice daily), 50 % to placebo (Riboavin capsules twice daily). Subjects recruited from 10 US sites. Inclusion criteria include subjects of either gender; ages 3080 years; \4 years from time of diagnosis; expected survival at least 3 years; able to give informed consent; MMSE [ 24. Exclusion criteria include modied UMSARS 1 score [17; tetrabenazine, rasagiline or selegiline; abnormal liver function tests; medications affecting autonomic function; neuroleptics; dementia. Primary outcome measure will be rate of change from baseline to 12 months in total UMSARS 1 score. Secondary outcome measures will include change from baseline to completion in total UMSARS score; slope analysis of rate of progression in total UMSARS score from baseline to 12 months; change from baseline to 12 months in UMSARS subscores. Results: The original study was funded by NINDS as a 2 center study. It was subsequently expanded under the Autonomic Rare Disease Consortium to a multicenter (10 sites) study conned to the United States of America. Recruitment commenced in April 2011 with the goal of recruiting 100 subjects over 2 years. By April 2012 we had completed recruitment. Subjects were predominantly white (90 %) and elderly (60.9 8.4 years), with a slight predominance of males (M:F, 62:38) and a ratio of MSA-C:MSA-P of 58:42 %. Ratio of Probable:possible MSA was 57:43 %. UMSARS Score: UMSARS I (excluding Q11) was 12.5 3.6, indicating mild-moderate symptoms and impairment of activities of daily living. UMSARS II was 15.9 4.6. UMSARS IV was 2.1 0.8. COMPASS_select was 14.7 11.8. Most severely affected domains were those of orthostatic intolerance, bladder dysfunction and sleep disorder. Dropouts thus far have comprised 4 subjects. There have been 1 death and 3 completions. Conclusions: The goal of recruiting 100 subject with relatively mildmoderate MSA within 24 months has been accomplished in 12 months. We chose 10 centers with a heavy research interest and strong autonomic emphasis. Patients were evenly distributed between possible and probable MSA. There was a slight predominance of MSA-C over MSA-P. It is feasible to recruit early MSA. Rifampin has been well-tolerated and its toxicity has been manageable. Patient compliance has been high with only 4 subjects dropping out to date.

New York University Medical Center, New York, NY, USA; Hospital de Cruces, Bilboa, Spain

Orthostatic hypotension (OH) dened as a reduction of systolic blood pressure of at least 20 mmHg or diastolic blood pressure of at least 10 mmHg within 3 min of active standing or head-up-tilt (HUT) is common in Parkinson disease (PD). We compared the frequency of OH when assessed by head-up-tilt test (HUT) versus active standing in 233 patients with PD. 116 patients (73 men and 43 women) underwent a 60 HUT and 117 patients (62 men and 53 women) underwent an active standing procedure. Blood pressure and heart rate were measured before and after 3 min in the upright position. The average dose of levodopa and direct dopaminergic agonists and the frequency of other medications was similar in both cohorts. The prevalence of OH was 70 % in those undergoing HUT and 41 % in those undergoing active standing (p \ 0.001). However, patients undergoing HUT were signicantly older (72.1 vs. 61.2 years, p \ 0.001) and had higher systolic blood pressure while supine (151 vs. 134 mmHg, p \ 0.001). Prevalence of OH by age showed that the 4050 years old group (n:15) had 20 % prevalence of OH with HUT versus 40 % with active standing (NS); in the 5060 years old group (n:38), 33 % had OH with HUT versus 47 % with active standing (NS), in the 6070 years old group (n:67), 78 % had OH with HUT versus 43 % with active standing (p \ 0.004), and in the 7080 years old group (n:85), 60 % had OH with HUT and 36 % with active standing (p \ 0.04). Thus, in younger patients with PD active standing and HUT showed similar prevalence of OH. However, among PD patients 60 years and older the prevalence of OH was signicantly higher with HUT than active standing. These ndings have practical implication for diagnosis and clinical management.

Poster #3 Cerebellar and parkinsonian phenotypes in multiple system atrophy (MSA). Similarities and differences
D. Roncevic, J. Martinez, L. Norcliffe-Kaufmann, H. Kaufmann New York University Dysautonomia Center, New York, NY, USA Based on the predominant motor abnormality, two MSA clinical phenotypes are identied: parkinsonian (MSA-P) and cerebellar (MSA-C). It is unclear whether in addition to the motor decit there are other signicant differences between these phenotypes. We reviewed clinical data from 97 patients with possible (12 %) or probable (88 %) MSA based on Consensus criteria, from the database of the NYU Dysautonomia Center. Of these, 60 % were classied as MSA-P and 40 % as MSA-C. Age at rst visit was similar in MSA P and C (both 61). Brain MRIs were more frequently abnormal in MSAC than MSA-P patients (93 vs. 51 %; p \ 0.001), the predominant abnormality being cerebellar and pontine atrophy. Autonomic symptoms preceded motor abnormalities in 59 % of MSA-C versus 44 % of MSA-P patients. Autonomic symptoms were felt 2.8 + 2.4 years before motor decits in both phenotypes. Forty-four patients had an appropriate trial of levodopa; 70 % had poor or no motor response, while 30 % had an initial, but short-lived good response to levodopa. Of those with good response, 93 % had MSAP. Orthostatic hypotension, at least 20/10 mmHg within 3 min of tilt, occurred in 85 % of MSA-C and 79 % of MSA-P patients, while a fall of 30/15 mmHg occurred in 69 %, both in MSA-C and MSA-P. Heart rate variability was similarly reduced in both phenotypes. Absence of blood pressure overshoot during phase IV of Valsalva maneuver was recorded in 86 % of MSA-C versus 66 % of MSA-P

Poster #2 Orthostatic hypotension in Parkinson disease: passive tilt vs. active standing
J. Martinez1, J.C. Esteban Gomez2, B. Tijero Merino2, K. Berganzo2, H. Kaufmann1

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234 (p \ 0.05). Plasma concentration of norepinephrine, supine and upright was similar in both phenotypes. In sum, MSA-C and MSA-P patients had similar gender distribution, age of rst visit, and frequency of OH. MSA-C patients more often had autonomic symptoms as the rst abnormality. They also had more abnormal MRIs, more frequently abnormal Valsalva maneuver and less response to levodopa.

Clin Auton Res (2012) 22:207258 of Automatic Control Engineering, Feng Chia University, Taichung, Taiwan Objectives: Differential diagnosis between vascular parkinsonism (vP) and idiopathic Parkinsons Disease (PD) is often difcult, due to the overlap in clinical presentation. The aim of the study was to use cerebral blood ow (CBF) regulation study to distinguish the two conditions and the mechanism of control of CBF. Materials and methods: We studied fourteen PD (6 female and 8 male; age = 58.3 + 12.2 years), 16 vP (2 female and 14 male; age = 71.3 + 8.9 years) and 10 normal subjects (NL) (3 female and 8 male; age = 56.5 + 8.6 years) as control group, who had undergone a simultaneously continuous TCD and beat-to-beat BP (CBP) monitoring. Several TCD markers and cross-correlation analysis (CCF) of CBF and BP were used to establish the status of CBF regulation. Results: The TCD PI resulted signicantly higher in VP (PI = 1.05 + 0.28) than in NL (0.79 + 0.16) but higher compared to PD (0.85 + 0.18). The percentage of decrease of CBF velocity in TCD during tilting resulted signicantly higher in vP (23.8 + 15.3 %) than in NL (8.5 + 12.7 %) but higher compared to PD (18.2 + 8.2 %). We found that a cut-off of PI [1.2 could differentiate PD from VP with a 100 % specicity and a 60 % sensitivity. CCF coherence (the percentage of number with correlation [0.5) was signicantly higher in NL (90 %) compared to PD (61.5 %) and vP (37.5 %). Phase shift in CCF showed good coupling in NL with 1.9 + 0.8 beats shift but graded loss of coupling on CBF and BP in PD and vP (phase shift = 3.4 + 1.0 and 2.8 + 1.1 beats respectively). Conclusions: PI and dynamic change of CBF in tilting can be used to differentiate vP and PD with a good degree of certainty. In healthy subjects, the CBF regulation is active even during the steady equilibrium state between normal physiological BP range. Graded loss of coupling between CBF and BP is positively related to PD and vP.

Poster #4 A novel quantitative index of baroreexsympathoneural function: application to patients with chronic autonomic failure
F. Rahman1, D.S. Goldstein2 1 Internal Medicine Residency Program, Boston University, Boston, MA, USA; 2Clinical Neurocardiology Section, NINDS/NIH, Bethesda, MD, USA Background: Beat-to-beat blood pressure and heart rate recordings during the Valsalva maneuver can be used to evaluate baroreex function without pharmacological manipulations. One can calculate baroreex-cardiovagal gain (BCG) from the slope of the relationship between cardiac interbeat interval and systolic blood pressure during the fall in pressure in Phase II. Failure of blood pressure to increase from its nadir at the end of Phase II and lack of a pressure overshoot in Phase IV constitute qualitative means to assess baroreex-sympathoneural function. Here we report a simple quantitative index of baroreex-sympathoneural function based on beat-to-beat systolic pressure during and after the Valsalva maneuver and application of this method in patients with chronic autonomic failure syndromes. Low frequency power of heart rate variability from power spectral analysis has been proposed as an index of the ability to modulate autonomic outows by baroreexes. Method: Using the trapezoid rule, we calculated areas below the baseline systolic pressure in Phases II and IV of the Valsalva maneuver in a total of 288 subjects, including patients with chronic autonomic failure manifested by orthostatic hypotension in Parkinson disease, multiple system atrophy, or pure autonomic failure. BCG and the log of low frequency power were measured in the same subjects. Orthostatic fractional changes in plasma norepinephrine provided a neurochemical index of baroreex-sympathoneural function. Results: The sum of baroreex areas in Phases II and III-IV was higher in patients with Parkinson disease with orthostatic hypotension, pure autonomic failure, or multiple system atrophy than in controls (p \ 0.00001 each). Individual values for the log of baroreex total area correlated negatively with the log of BCG (r = -0.47, p \ 0.0001), the log of low frequency power (r = -0.47, p \ 0.0001), and the orthostatic fractional increase in plasma norepinephrine (r = -0.35, p \ 0.0001). Interpretation: The baroreex areas method provides a quantitative index of baroreex-sympathoneural function.

Poster #6 Temperature prole in congenital central hypoventilation syndrome (CCHS) and rapid-onset obesity with hypothalamic dysfunction, hypoventilation, and autonomic dysregulation (ROHHAD): ibutton measures of peripheral skin temperature
R. Saiyed, C.M. Rand, M.S. Carroll, P.P. Patwari, T. Stewart, C. Koliboski, D.E. Weese-Mayer Ann and Robert H Lurie Childrens Hospital of Chicago, Chicago, IL, USA Rationale: Human body temperature results from a balance of heat production/loss, varies diurnally, and is driven by an endogenous circadian rhythm. Peripheral skin temperature, measured at distal extremities, is inversely related to core body temperature but typically offset by 1 h. Preliminary data suggest altered temperature/circadian regulation patterns in CCHS and ROHHAD, both disorders of respiratory and autonomic control. These data, coupled with anecdotal observations of cool extremities in both disorders, led us to hypothesize that children with CCHS and ROHHAD will have reduced peripheral skin temperature (vs. controls) and that children with ROHHAD will demonstrate an augmented variability in temperature patterns (vs. controls). Methods: Study subjects included 14 cases (7 PHOX2B mutationconrmed CCHS cases, 7 phenotypically conrmed ROHHAD cases) and 9 healthy controls. Peripheral skin temperature was measured with the Thermochron iButton, (Maxim, Dallas), afxed to a cotton

Poster #5 Loss of cerebral blood ow rhythm in Parkinsons disease and vascular parkinsonism
S.-J. Yeh1, B.-W. Chang2, B.-Y. Liau2, C.-C. Chiu3 1 Department of Neurology, Cheng-Ching Hospital, Taichung, Taiwan; 2Hong-Kong University, Taichung, Taiwan; 3Department

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Clin Auton Res (2012) 22:207258 wrist-band, with temperature measures every 3 min, for a period of *96 h. Results: Compared to controls, CCHS cases had signicantly lower daytime (31.8 vs. 32.5, p \ 0.01) and nighttime (32.5 vs. 33.6, p \ 0.001) mean peripheral skin temperature. Compared to controls, children with ROHHAD had a trend toward lower mean daytime peripheral skin temperature (32.1 vs. 32.5, NS) and a signicantly higher nighttime mean peripheral skin temperature (34.1 vs. 33.6 p \ 0.01). Conclusions: These results conrm our hypotheses of altered peripheral temperature regulation patterns in CCHS and ROHHAD. CCHS cases exhibited lower overall temperatures with an attenuated diurnal variation, while wide uctuations in peripheral temperatures were characteristic of ROHHAD cases. These data serve to comprehensively characterize temperature proles and related dysregulation in this cohort and begin to unravel the distinct mechanisms of temperature regulation in these related disorders of respiratory and autonomic regulation.

235 Conclusion: These ndings demonstrate an important difference in a childs response to variable stimuli. While anxiety was reduced following clown-intervention, the SNS tone increased contrary to our hypothesissuggesting that similar, unexpected ndings may be present in other activities involving environmental stimuli in hospitalized children.

Poster #8 Cardiac stroke volume and sympathetic/ parasympathetic measurements increase the sensitivity and specicity of HUTT in children and adolescents
M.T. Numan, J.E. Lankford, A. Gourishankar, I.J. Butler Department of Pediatric Cardiology, Center of Dysautonomia, University of Texas, Houston, TX, USA Head up tilt table test (HUTT) is gold standard in evaluating autonomic dysfunction and syncope in children and adolescents. Limitations of conventional HUTT, cycling blood pressure (BP) every one to 2 min, with heart rate (HR) correlated with patient symptoms, has low sensitivity and specicity. Investigators have evaluated more reliable and sensitive physiological parameters to increase predictability of HUTT. From May 2009 to May 2012 we performed 422 HUTT evaluations on children and adolescents. The rst group of 152 patients had conventional HUTT, including HR, arm cuff BP, and oxygen saturation recorded every minute for 10 min while supine, for 30 min while head up 70o and for 10 min with supine reposition while recording patient symptoms. The second group included 270 patients with HUTT using Task Force Monitor with display and storage of continuous BP, HR, cardiac stroke volume (SV) by trans-thoracic impedance and calculated sympathetic and parasympathetic activity correlated with symptoms and signs. Median ages were 12.5 and 13.2 years in group one and two, respectively. Patients from both groups were referred by pediatric neurologists, cardiologists, gastroenterologists and rheumatologists with syncope (63 %), dizziness (88 %), lightheadedness and headaches (52 %), chronic nausea and stomach pains (32 %), chronic fatigue (42 %), convulsions (6 %), bromyalgia (2 %), palpitations and chest tightness (12 %) and metabolic disorders (10 %). A positive test was dened in group one as severe symptoms of syncope, blackout, vomiting, severe headache, excessive fatigue and tremors or convulsions accompanied by changes in HR (tachycardia, bradycardia) and/or blood pressure. In group two, similar symptoms were accompanied by signicant changes in HR, BP, cardiac SV and sympathetic/parasympathetic activity. There was increased ability to correlate clinical manifestations with physiological abnormalities on HUTT in the second cohort of subjects and also an increased sensitivity of the test to determine whether there was orthostatic intolerance

Poster #7 Heart rate variability in hospitalized children: autonomic response to laughter and engagement
P.P. Patwari1, M.S. Carroll1, K. Gray2, M.K. Janda2, A.S. Kenny1, T.H. Stewart1, C. Brogadir1, S.H. Wang3, D.M. Steinhorn3 1 Center for Autonomic Medicine in Pediatrics, Childrens Memorial Hospital in Chicago, IL, USA; 2Pediatrics, Childrens Memorial Hospital in Chicago, IL, USA; 3Pediatric Critical Care, Childrens Memorial Hospital in Chicago, IL, USA Introduction: With growing evidence of autonomic nervous system (ANS) function as a biomarker in disease and the importance of environment in recovery, we proposed that effects of enjoyable intervention (affecting hospital environment) in children could be quantied through the ANS measure of heart rate variability (HRV). We hypothesized that the induction of laughter from clown exposure would relieve stress, distinct from quiet engagement with measurable changes in the ANS response resulting in increased parasympathetic (PSNS) and decreased sympathetic (SNS) tone. Methods: Hospitalized children without fear of clowns, heart rate altering medication, or hearing/visual/development impairment were recruited. Primary dependent variables were State-Trait Anxiety Inventory (STAI) for children and adolescents and HRV metrics (noninvasive monitoring; NOX-T3;CareFusion,CA). Subjects were exposed to active engagement (Clown Care, Big Apple Circus) and quiet engagement (quiet project with volunteer) with cardiorespiratory monitoring prior to, during, and after intervention. Waveforms were exported and analyzed with custom MATLAB software to calculate normalized measures for a 3-min segment of each condition. Values for HRV included: standard deviation of the NN interval (SDNN), high frequency (HF, 0.150.4 Hz) reecting PSNS tone, and low frequency (LF, 0.040.15 Hz) ratio [LF/(HF + LF)] reecting SNS tone. Results: The Pilot Cohort included 48 subjects: mean age 10.5 years (range: 5.317.9). Mean STAI scores reect a signicant reduction in anxiety after both interventions (mean SD: Baseline 50 14; Post-clown 44 10; Post-volunteer 44 10; p \ 0.05 pre/post t test). We found a reduction in mean SDNN with only volunteerintervention (Baseline 60.5 5.3; post-volunteer 44.8 4.2; p \ 0.05), signicant increase in SNS with only clown-intervention (Baseline 0.488 0.018; post-clown 0.514 0.017; p \ 0.05). No signicant change in PSNS tone with either intervention.

Poster #9 Biogenic amine metabolism in juvenile neurocardiogenic syncope with dysautonomia

I.J. Butler, J.E. Lankford, M.T. Numan Department of Pediatric Neurology, Center for Dysautonomia, University of Texas at Houston Medical School, Houston, TX, USA

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236 In a cohort of children and adolescents with neurocardiogenic syncope and dysautonomia with physiological abnormalities on head up tilt table testing (HUTT), seventeen youngsters had a diagnostic lumbar puncture to evaluate persistent daily headaches. In addition to opening cerebrospinal uid (CSF) pressure and routine analyses, biogenic amine and biopterin metabolites were quantied by high performance liquid chromatography (Medical Neurogenetics, Atlanta, GA). There were seventeen subjects (14 females), aged 12.520.5 years and one subject had two lumbar punctures 5 years apart. Serotonin metabolite levels of 5-hydroxyindoleacetic acid (5HIAA) were decreased in eleven subjects and dopamine metabolite levels of homovanillic acid (HVA) were decreased in eleven subjects. Twelve subjects had a defect in either 5HIAA and/or HVA metabolites. Neopterin was decreased in one only subject with normal biogenic amine metabolites and one subject had a low CSF 5-methyltetrahydrofolate level (cerebral folate deciency with folate receptor antibodies). Patients with decient 5HIAA and HVA levels showed more severe clinical symptoms during HUTT and were less tolerant of upright posture. Defects in peripheral catecholamines have been evaluated in adults with dysautonomia and defects in peripheral serotonin levels have been observed in migraine patients. This study indicates that there are defects in dopamine and serotonin in the central nervous system in juvenile onset neurocardiogenic syncope with dysautonomia. Normal CSF levels of biopterin metabolites (neopterin and tetrahydrobiopterin) in subjects with defective biogenic amine levels do not indicate a metabolic defect in biogenic amine biosynthesis. One subject showed a severe decrement in HVA levels over an interval of 5 years. A neurodevelopmental defect in biogenic amines in the central nervous system should be further evaluated in juvenile onset neurocardiogenic syncope and dysautonomia. Clinical correlation with severity of orthostatic intolerance and biogenic amine decits is an interesting observation.

Clin Auton Res (2012) 22:207258 performance of the Asian Tummo meditation technique a deep breathing pattern with a Valsalva-like pattern was evidently visible in the blood pressure and heart rate recordings. With meditation, the cardiovascular reactions during the forced respiration, Valsalva maneuvers and cold pressure test were all normal, although the responses were more evident compared to the control situation. During the head-up tilt the Valsalva-like pattern in blood pressure and heart rate was more pronounced which resulted in large shifts in blood pressure and heart rate during the head-up tilt with phases of severe hypotension followed by recovery phases. Conclusions: During the performance of the Asian Tummo meditation, the breathing pattern combined with whole body tensing results in a Valsalva-like pattern in blood pressure and heart rate. No actual inuence of the meditation technique on the autonomic nervous system nor on the responses during the autonomic function tests was observed.

Poster #11 Evidence for central sensitization in bladder pain syndrome from the ICEPAC trial (interstitial cystitis: elucidation of psychophysiologic and autonomic characteristics)preliminary psychometric ndings
J.W. Janata1, F. Daneshgari1, C.A.T. Bufngton2, G. Chelimsky3, M.D. Louttit1, D. Zhang4, T.C. Chelimsky3 1 University Hospitals Case Medical Center, Cleveland, OH, USA; 2 The Ohio State University, Columbus, OH, USA; 3Medical College of Wisconsin, Milwaukee, WI, USA; 4Case Western Reserve University, Cleveland, OH, USA Background: Interstitial cystitis (ICBladder Pain Syndrome), is characterized by pain in the bladder worse when full and better when empty along with urgency and frequency. Despite extensive research, the pathophysiology is unknown and there is no effective treatment. ICEPAC aims to evaluate psychophysiologic contributions to this disorder in general and to elucidate the role of central processing in particular. Methods: ICEPAC completed enrollment will include 76 women with IC, 76 women with myofascial pelvic pain disorder (MPP), 38 1st degree female relatives of IC subjects without pelvic pain, and 38 healthy age-matched women. Subjects complete comprehensive psychological measures of pain, function, catastrophizing, childhood trauma, PTSD, somatization, anxiety and stress. A subset of patients also undergo a Trier stress test, with assessment of the resulting catecholaminergic and hypothalamic-pituitary response. Results: Initial recruitment has included 50 subjects: 22 with IC/MPP, 7 with MPP alone and 21 healthy controls. Ages ranged from 18 to 62. Compared to healthy controls, the pain groups show elevated levels of somatization, depression, anxiety, PTSD symptoms, pain catastrophizing and childhood trauma, and both groups show impairment of function. However, the IC/MPP group compared to the MPP group has signicantly higher scores on childhood emotional abuse (mean = 12.4 vs. 9.0), PTSD symptoms (13.3 vs. 5.1), and pain catastrophizing (28.0 vs. 16.6). Conclusion: These results are consistent with early exposure to trauma and subsequent central nervous system sensitization evidenced by PTSD symptoms and increased emotional processing of nociceptive input. These promising early ndings require the conrmation that additional recruitment will provide. Evidence for autonomic signatures or correlates is pending continued recruitment.

Poster #10 The iceman revisited: autonomic function tests during performance of the Asian Tummo meditation technique
J.T. Groothuis1,2, M.T.E. Hopman1 1 Department of Physiology, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands; 2Department of Rehabilitation, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands Background: The world record holder of full-body ice immersion claims he can inuence his autonomic nervous system through the Asian Tummo meditation technique. We previously demonstrated (AAS 2010) that he did not demonstrate the typical immediate blood pressure or heart rate elevation during submersion into ice (water). To assess whether he can actually inuence his autonomic nervous system, we performed autonomic function tests with and without meditation. Methods: We performed different autonomic function tests, i.e. Valsalva maneuver, forced respiration, head-up tilt and a cold pressure test of the hand, on a 53 year old male (the Iceman) on two different days; once in a normal control situation without any meditation technique, whilst during the other occasion he was performing the Asian Tummo meditation technique. Blood pressure and heart rate were measured continuously using an automatic blood pressure device (Nexn). Results: Without mediation, the cardiovascular reactions on the autonomic function tests were completely normal. During the

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237 1 adrenergic agonist, midodrine. We studied 34 patients who had a similar pressor response to atomoxetine (18 mg) and midodrine (510 mg), dened a priori as an increase in at least 15 mm Hg in seated systolic blood pressure (SBP), 60 min after drug administration. Both, atomoxetine and midodrine increased seated SBP by 32 (95 % CI: 23.440.9, P \ 0.001) and 30 mm Hg (95 % CI: 21.139.1, P \ 0.001), respectively compared with placebo. No difference in seated SBP was observed between atomoxetine and midodrine. In contrast, atomoxetine had a greater pressor response on standing. Atomoxetine increased standing SBP by 12 mm Hg (95 % CI: 0.622.4, P = 0.039), compared with midodrine. Of note, both atomoxetine and midodrine signicantly improved pre-syncopal symptoms. Atomoxetine reduced the lightheadedness score by 2 points (95 % CI: 0.073.53, P = 0.04), compared to baseline. Similarly, midodrine reduced the lightheadedness score by 2 points (95 % CI: 0.493.51, P = 0.01), compared to baseline score. In conclusion, atomoxetine has a greater effect on orthostatic tolerance as dened by standing systolic blood pressure compared with midodrine.

Poster #12 The antiemetic efcacy of carbidopa: a randomized, double-blind, placebo-controlled, crossover study in patients with familial dysautonomia
L. Norcliffe-Kaufmann, J. Martinez, F. Axelrod, H. Kaufmann New York University Dysautonomia Center, New York, NY, USA One of the most disabling features of patients with familial dysautonomia (Riley Day syndrome, hereditary autonomic and sensory neuropathy type III) are recurrent vomiting attacks that can last for hours and are associated with high levels of circulating dopamine. None of the available treatments are effective. To determine whether treatment with carbidopa, a competitive inhibitor of the enzyme dopa decarboxylase that blocks the synthesis of dopamine outside the brain, can improve symptoms we enrolled 12 patients with FD in an openlabel titration and treatment study. This was followed by a randomized, double-blind, placebo-controlled crossover study to evaluate its antiemetic efcacy. Symptoms severity was measured daily on a validated patient reported outcome scale (Rhodes Index) and at scheduled ofce visits (Global Clinical Impression of Severity Scale). Vomiting was prevented by previous fundoplication surgery in each case, but all patients experienced severe cyclical nausea and uncontrollable retching that was refractory to standard treatments. Average daily dose of carbidopa was 480 mg (range 325600 mg/day) and was well tolerated. Twenty-four hour urinary dopamine excretion was signicantly lower while on carbidopa (147 32 ug/g crt) than at baseline (271 41 ug/g crt, p \ 0.0001). In the double-blind phase, patients experienced signicantly less nausea and retching each day while on carbidopa than while on placebo (composite Rhodes Index score: carbidopa 6.9 2.2 vs. placebo 9.7 2.5, p \ 0.0001). Patients also reported that their symptoms were less severe on carbidopa compared with placebo at scheduled study visits (Global Clinical Impression of Severity: 2 0.5 vs. 4 1 units, p \ 0.02). We conclude that carbidopa inhibits the formation of dopamine in the periphery and is a safe, effective antiemetic in patients with FD.

Poster #14 Benecial effects of oral rehydration solution on orthostatic intolerance

M.S. Medow, D. Tewari, A. Aggarwal, Z. Messer and J.M. Stewart Department of Pediatrics, New York Medical College, Valhalla, NY, USA Background and Aim: OI can cause excessive upright heart rate (HR), and blood pressure (BP) decreases, initiated by postural contraction of central blood volume (CBV) by translocation of blood from the upper to lower body. Intravenous isotonic saline (IVS) CVB expansion effectively reduces OI regardless of etiology; oral hydration fails to provide similar benet. ORS (glucose + sodium) efciently rehydrates cholera patients, suggesting it can increase CBV. We propose that equal volumes of ORS or IVS can improve orthostatic tolerance by mitigating changes in HR and BP in fainting patients. Methods: We studied subjects with OI (N = 4), with 3 postural faints during the past year or Postural Orthostatic Tachycardia Syndrome, and healthy controls (N = 4), and separately evaluated baseline (no treatment), IVS and ORS. Orthostasis using Lower Body Negative Pressure (LBNP) was applied sequentially at -15, -30, -40 mmHg for 5 min each, and -55 mmHg for 1 h or until OI was elicited. Results: While controls tolerated -55 mmHg, fainters could not. Controls became tachycardiac with decreased pressure (32.4 % HR increase from baseline), but fainters HR remained unchanged during LBNP. In fainters, IV saline and ORS resulted in heart rate increases at -40 mmHg, signicantly greater (p \ 0.05) than baseline. In controls, mean arterial pressure (MAP) remained unchanged from baseline to -40 mmHg, but decreased signicantly (43.7 %, p \ 0.01) in fainters. Following IV saline in fainters, MAP fell signicantly comparing baseline to 40 mmHg (76.5 7.2 vs. 54.9 2.4, [p \ 0.05]). In contrast, ingestion of ORS by fainters prevented this decrease as MAP remained unchanged (78.1 9.2 vs. 75.5 5.5 mmHg, baseline vs. -40 mmHg). Conclusion: This pilot study suggests ORS may be benecial in decreasing orthostasis in fainters, possibly afforded by allowing appropriate increases in HR and BP maintenance, thereby avoiding syncope. ORS may be a practical, cost-effective alternative to IVS for OI management.

Poster #13 Comparative efcacy between the norepinephrine transporter blocker, atomoxetine, against midodrine for the treatment of orthostatic hypotension
C.E. Ramirez, L.E. Okamoto, A. Gamboa, S.R. Raj, A. Diedrich, D. Robertson, I. Biaggioni, C. Shibao Department of Medicine, Division of Clinical Pharmacology, Vanderbilt University School of Medicine, Nashville, TN, USA Orthostatic hypotension is the hallmark of autonomic failure. Patients usually require medication to prevent the blood pressure fall and presyncopal symptoms on standing position. We have previously reported that atomoxetine, a norepinephrine transporter blocker that potentiates residual sympathetic tone, has a pressor effect in autonomic failure. The aim of this study was to test the hypothesis that for the same pressor response, atomoxetine is more effective on improving blood pressure on standing and reducing pre-syncopal symptoms compared with the alpha-

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Clin Auton Res (2012) 22:207258 Methods: This IRB-approved prospective study compared HRV in the supine and upright positions in 14 healthy females [18 years screened for diseases with autonomic abnormalities, and 20 subjects with either interstitial cystitis or myofascial pelvic pain. The tilt study was divided into 5 min of supine rest, 10 min upright epochs, and the last 5 min of supine rest. The study compared the 2 periods of supine rest with the rst upright epoch. Standard time and frequency domain measures were compared using students t test for groups with unequal variance. Results: Demographic variables were not different in the 2 populations. Mean RR interval supine in pelvic pain subjects was 849 170 ms (71 bpm) compared to 1,000 218 ms (60 bpm) in healthy subjects (p = 0.004), and upright 733 134 ms (82 bpm) versus 853 135 (70 bpm, p = 0.05). RMSSD was 44 42 versus 76 59 (p = 0.02) supine, and 23 15 versus 44 39 upright (p = 0.07). Conclusion: Women with pelvic pain have signicantly higher heart rates at rest and standing compared to healthy women with significantly less variability. Their values at rest are nearly identical to the those of healthy women standing suggesting that their resting sympathetic tone may be at the level of standing healthy sympathetic tone.

Poster #15 Musculoskeletal evaluation of patients with interstitial cystitis

T.V. Sanses1, G. Chelimsky2, D. Zhang3, J. Janata1, T. Mahajan1, B. Fenton4, A. Askari1, R. Elston3, T. Chelimsky2, ICEPAC Study Group3 1 University Hospitals Case Medical Center, Cleveland, OH, USA; 2 Medical College of Wisconsin, Milwaukee, WI, USA; 3Case Western Reserve University, Cleveland, OH, USA; 4SUMMA Health System, Akron, OH, USA Objectives: To determine the distribution and correlations of pain across ve body locations in women with Interstitial Cystitis (IC) and healthy age-matched women. Background: We hypothesized that deep muscular pelvic pain in patients with IC is due to a generalized pain disorder with altered afferent signaling. Therefore, the pain is not limited to the pelvic area, but rather a more centralized disorder. Methods: Interstitial Cystitis Elucidation of Psychophysiologic and Autonomic Characteristics study (ICEPAC) is a multicenter prospective cohort trial. Subjects underwent muscular tender point assessment in 5 areas: general body, abdomen, inguinal, inner thigh, and pelvic area. Pain was assessed using a 010 Numeric Rating Scale (NRS). We calculated the overall intraclass correlation (ICC), where the classes are the body locations, and the 10 pairwise correlations across the 5 locations of pelvic, body, lower extremity, abdominal and inguinal tender points. Positive pairwise correlations and overall ICC would support our hypothesis. Results: We examined 17 patients with IC and 20 healthy age-matched women. We found no difference in age and weight between the groups. The range of mean NRS pain scores for different body locations in subjects with IC was 4.15.2 and in healthy controls 0.21.0. The mean pelvic NRS pain score in subjects with IC was higher 4.91 3.34 than in healthy controls 0.19 0.31, p \ 0.01. The ICC coefcients for women with IC and healthy age-matched controls were positive 0.58 and 0.541, respectively. Within the group of women with IC, the pairwise correlation coefcients were high between pelvic and abdominal (0.70), and between pelvic and inguinal (0.73) muscle groups. Similar but smaller correlations were noticed in healthy controls. Conclusions: Muscular, including pelvic, pain in women with IC could be due to a generalized pain disorder with altered afferent signaling. These results will be conrmed after the nal enrollment is completed.

Poster #17 Study of the P2X2 and 7 receptors in the enteric glial cells of ileum rat subjected to ischemia and reperfusion
C.E. Mendes1, K. Palombit1, W. Tavares de Lima2, P. Castelucci1 1 o Paulo, Brazil; Department of Anatomy, University of Sa 2 o Paulo, Brazil Department of Pharmacology, University of Sa Intestinal ischemia/reperfusion (I/R-i) injury is a common problem in hospitalized patients, and is associated with high morbidity and mortality in both surgical and trauma patients. The enteric neurons and glial cells are affected in the ischemia. The aim was to study the effect of I/R-i on enteric glial cells, neurons and P2X2 and 7 receptors. The ileal artery was occluded for 35 min with an atraumatic vascular clamp. The animals were sacriced after 0 h (h), 24 h, and 14 days (d) after ischemia. Sham-operated groups were subjected to identical manipulations without the arterial occlusion. The tissues were prepared for double marking of P2X2 and 7 receptors with anti-Hu (pan-neuronal), S100 (glial marker), and glial brillary acidic protein (GFAP/glial marker). The P2X2 receptor-IR cells co-localized 90 % with anti-Hu-IR neurons and 30 % with S100-IR glial cells in all groups. P2X7 receptor-IR co-localized 100 % with anti-Hu-IR neurons and S100-IR glial cells in all groups. S100-IR co-localized 70 % with GFAP-IR glial cells, and anti-Hu-IR not co-localize with GFAP in all groups. The density (cell/cm2) of P2X2-IR/cm2 decreased by 18, 13, 3 %, and P2X7-IR/ cm2 decreased by 8, 10 and 4 % in the 0, 24 h and 14 days I/R-i groups, respectively. Hu-IR/cm2 neurons decreased by 23 % (0 h), 21 % (24 h) and 13 % (14 days). S100-IR/cm2 decreased by 13 % only I/R-i 14d group, and GFAP-IR/cm2 increased by 19 % (0 h) 5 % (24 h) and 7 % (14 days) in the I/R-i groups. The prolife area (lm2) of anti-Hu-IR neurons did not differ statistically, and S100-IR glial cells decreased by 9 % in all groups. Our ndings indicate that the I/R-i is associated with alterations in the P2X2 and 7 receptors, enteric neurons and enteric glial cells that may result in changes motility intestinal.

Poster #16 Heart rate variability (HRV) in pelvic pain

P. Singh1, J. Thayer2, G. Chelimsky3, T. Chelimsky3 1 Case Western Reserve University, Cleveland, OH, USA; 2The Ohio State University, Columbus, OH, USA; 3The Medical College of Wisconsin, Milwaukee, WI, USA Background: HRV has not been studied in pelvic pain. Hypothesis: Based on other pain syndrome literature, HRV should reect heightened sympathetic and diminished parasympathetic function.

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239 chains is involved in regulation of esophageal sphincter contraction, muscular wall relaxation, blood vessel constriction, and augmented peristaltic activity. Little is known, however, regarding the effects of spinal cord injury (SCI) upon esophageal motility. Objective: To compare differences in esophageal motility between persons with SCI and able-bodied (AB) controls using high resolution manometry (Given Imaging, Duluth, GA). Methods: After fasting 12 h, a catheter containing multiple pressure sensors was introduced into the esophagi of subjects to a heightindexed depth to enable visualization of both upper and lower esophageal sphincters. Each subject performed 10 wet swallows while esophageal pressure topography and impedance were recorded at 116 different detection points along the probe. The mean amplitude of the propagating pressure wave (PPW), and the percentage of observed double peaked swallows (%DS) were recorded. Results: SCI group included 11 subjects. Duration of injury 142 years; mean age, 48 12 years. Mean PPW amplitude was signicantly decreased in the SCI group compared to the AB group (75 23 mmHg versus 140 61, respectively; p = 0.0171). %DS was signicantly increased in the SCI group compared to the AB group (28 19 and 5 8; p = 0.0169). Conclusion: The inability to generate adequate esophageal peristalsis in the SCI cohort suggests loss of esophageal autonomic control. The increase in %DS noted in the SCI group suggests a compensatory mechanism for bolus clearance. The clinical consequences of the observed non-specic esophageal motility disorder (NEMD) are not well understood, although limited studies in the able-bodied have demonstrated progression to achalasia in over 50 %. NEMD might therefore predispose to tracheobronchial aspiration and pneumonia in the SCI population. Studies are ongoing to examine the role of NEMD upon airway inammation and aspiration risk.

Poster #18 Brainstem neuropeptides and vagal protection of the gastric mucosal against injury: role of prostaglandins, nitric oxide and calcitonin-gene related peptide in capsaicin afferents
Y. Tache Cure: Digestive Diseases Research Center and Center for Neurovisceral Sciences & Womens Health, Digestive Diseases Division, David Geffen School of Medicine at UCLA and VA Greater Los Angeles Healthcare System, Los Angeles, CA, USA Earlier studies indicated that the integrity of vagal pathway was required to confer gastric protection against damaging agents. Several peptides located in the brainstem initially identied to inuence vagal outow to the stomach, as assessed by electrophysiological approach or by vagaldependent alterations of gastric secretory and motor function, were investigated for their inuence in the vagal regulation of gastric mucosa resistance to injury in conscious rats. Thyrotropin releasing hormone (TRH), or the stable TRH agonist, RX-77368, injected at low doses into the cisterna magna (ic) or the dorsal motor nucleus (DMN) protects the gastric mucosa against intragastric ethanol-induced gastric injury through stimulation of vagal cholinergic pathways, inducing the release of gastric prostaglandins/nitric oxide (NO) and the recruitment of efferent function of capsaicin sensitive afferent bers containing calcitonin-gene related peptide (CGRP). TRH antibody injected bilaterally into the DMN or ic prevented the adaptive gastric protection induced by intragastric administration of mild irritants (0.35 N HCl or 20 % ethanol) before strong irritants (0.6 N HCl, 60 % ethanol). Microinjection of TRH antibody bilaterally into the DMN abrogates the gastroprotection against 60 % ethanol induced by kainic acid microinjected into the raphe pallidus indicative that activation of endogenous TRH containing raphe-DMN projections play a role in adaptive gastric protection. Peptide YY, CGRP, adrenomedullin and corticotripin releasing factor injected intracisternally also protect against ethanol injury largely through similar peripheral effectors mechanisms than TRH. Synergistic interaction between RX77368 and PYY agonist [Pro34]PYY to confer gastroprotection against ethanol are observed when injected ic at subthreshold doses Therefore gastric prostaglandins and CGRP/NO pathways represent a common nal mechanism through which brain peptides confer vagally mediated gastroprotection against injury. A better understanding of brain circuitries through which these peptides are released will provide new strategies to recruit integrated and multifaceted gastroprotective mechanisms.

Poster #20 Real time change of prefrontal cortex activity related to normal and abnormal bladder lling in Parkinson disease: A functional near-infrared spectroscopy (fNIRS) study
C. Yamaguchi1, T. Uchiyama1,2, T. Yamamoto2, R. Sakakibara3, M. Fuse1,4, M. Yanagisawa4, T. Kamai5, T. Ichikawa4, K. Hirata6, S. Kuwabara2, T. Yamanishi1 1 Continence Centre & Department Neuro-urology, Dokkyo Medical University; 2Department of Neurology, Chiba University Graduate School of Medicine; 3Neurology Division, Department of Internal Medicine, Sakura Medical Center, Toho University; 4Department of Urology, Chiba University Graduate School of Medicine; 5 Department of Urology, Dokkyo Medical University; 6Department of Neurology, Dokkyo Medical University Patients with Parkinsons disease (PD) frequently have lower urinary tract dysfunction (LUTD). However, the mechanism of LUTD in PD has not been claried yet. We noninvasively showed the real time change of oxy-Hb in prefrontal cortex in patients with PD and evaluated the association between prefrontal cortex and LUTD in PD. We recruited 6 patients with PD, who were informed consent and different from the subjects in preliminary study last year; 3 women and 3 men; mean age 60 years (5561), untreated and 4 patients had detrusor overactivity during bladder lling. The fNIRS prove was placed on two area (right and left) of the subjects frontal head, and we measured oxy-Hb concentration in bilateral anterior parts of prefrontal cortex (may be Brodmanns area 9, 10) during bladder lling in cystometry by fNIRS (NIRO 200,

Poster #19 Autonomic dysfunction and esophageal dysmotility in persons with spinal cord injury
G.J. Schilero1,2, M. Radulovic1,2, C. Renzi1, C. Yen1, W.A. Bauman1,2,3, M. Korsten1,2 1 Rehabilitation Research and Development Center of Excellence for the Medical Consequences of Spinal Cord Injury, The James J. Peters Veterans Affairs Medical Center, Bronx, NY, USA; 2 Department of Medicine, The Mount Sinai School of Medicine, New York, NY, USA; 3Department of Rehabilitation Medicine, The Mount Sinai School of Medicine, New York, NY, USA Background: Parasympathetic innervation of the esophagus provides motor innervation to the muscular layer and secreto-motor innervation to glands. Sympathetic input arising from cervical and thoracic

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240 Hamamatsu Photonics Inc, Japan). The oxy-Hb concentration was calculated by the Beer-Lambert method. In patients with PD, oxy-Hb concentration gradually increased in bilateral anterior parts of prefrontal cortex from the start to end of bladder lling. However, regardless of the appearance of detrusor overactivity, this rate was smaller than our data in other subjects without detrusor overactivity. And the rate in patients with detrusor overactivity was smaller than that without detrusor overactivity. Furthermore, the specic change of oxy-Hb concentration was shown under detrusor overactivity during bladder lling in real time; oxy-Hb spontaneously increased at the beginning of detrusor overactivity and oxy-Hb concentration remarkably decreased under detrusor overactivity occurring. There was no signicant difference in oxy-Hb concentration between right and left prefrontal cortex. We showed the specic changes of oxy-Hb concentration synchronised with normal and abnormal bladder ling in bilateral prefrontal cortex of patients with PD by using fNIRS. In patients with PD, dysfunction of prefrontal cortex may be involved in LUTD, in particular detrusor overactivity.
1

Clin Auton Res (2012) 22:207258 Continence Center and Department Neuro-urology, Dokkyo Medical University; 2Department of Neurology, Chiba University Graduate School of Medicine; 3Neurology Division, Department of Internal Medicine, Sakura Medical Center, Toho University; 4Department of Urology, Chiba University Graduate School of Medicine; 5 Department of Urology, Dokkyo Medical University; 6Department of Neurology, Dokkyo Medical University Photo-stimulation using low reactive level laser was reported to have neurobiological effects. As these effects, inhibition of Ad- and C- bre nerve conductions, activation of central descending inhibitory system, and suppression of local synaptic neurotransmission were reported. Micturition reex is constructed by activation of peripheral Ad- and C- bre afferent nerves, and which is controlled by central descending inhibitory system. Then, the photo-stimulation will be applicable to modulate these neural controls. Therefore, we investigate the photo-stimulating effect of low reactive level laser on bladder dysfunction in neurological disease rats. Experiments were performed on adult male SpragueDawley rats with bilateral injections to substantia nigra of 6OHDA (PD model), spinal injury (SP model) or saline (Normal model). Cystometric investigation was performed, and interval time between voids, urine volume per void, and maximum bladder pressure during voiding were investigated. After 3060 min baseline recording, photo-stimulation using low reactive level laser or sham stimulation via prove was irradiated to bilateral L6/S1 intervertebral foramen transcutaneously via the probe contacted to body or directly via the probe non-contacted to body. Recording after the stimulation was continued for several hours until micturition cycle returned to baseline. Compared with the baseline record, in indirect and direct sham-stimulated groups in each model, interval time between voids and urine volume per void were not unchanged. Both in indirect and direct photo-stimulated groups in each model, interval time between voids and urine volume per void was signicantly increased. These changes were stimulation-time dependent. In any groups, maximum bladder pressure was unchanged. Photo-stimulation using low reactive level laser to bilateral L6/ S1 root modulated storage function but not voiding function in each model. These effects may be considered to be inhibition of afferent nerve conduction, activation of central descending inhibitory system, and suppression of local synaptic neurotransmission, as well as analgesic effect.

Poster #21 Effect of Brilliant Blue G on P2X7 receptor after intestinal ischemia and reperfusion
K. Palombit1, C.E. Mendes1, W. Tavares de Lima2, P. Castelucci1 1 o Paulo, Brazil; Department of Anatomy, University of Sa 2 o Paulo, Brazil Department of Pharmacology, University of Sa In pathological conditions including ischemia, the extracellular ATP can reach high levels, activating the P2X7 receptor. Several studies have shown that injury can be attenuated by the antagonist of P2X7 receptor, the Brilliant Blue G (BBG). In the present work, we analyzed the effects of the BBG on the P2X7 receptor and ileum myenteric plexus of rats after intestinal ischemia and reperfusion (I/R). The ileal artery was occluded for 45 min with an atraumatic vascular clamp. BBG (50 and 100 mg/kg) or saline (vehicle) was given subcutaneous 1 and 24 h after injury (I/R 24 h group). In the I/R 14 days group, BBG was given 1 h and once daily for the next 5 days. We too analyzed I/R 0 h group (not reperfusion). Myenteric neurons were evaluated for immunoreactivity against the P2X7 receptor, nitric oxide synthase (NOS), neurolament (NF) and choline acetyl transferase (ChAT) (n = 5). P2X7 receptor-IR was observed to co-localize 100 % with NOS-IR, NF-IR and ChAT-IR neurons in all groups. The neuronal density (neurons/cm2) of the I/R 0 h group was decreased by 40 % of P2X7IR, NOS-IR, NF-IR and ChAT-IR neurons. In the I/R 24 h saline group the density of P2X7-IR, NOS-IR, NF-IR and ChAT-IR neurons was decreased by 19, 46, 59 and 30 %, respectively, and in the BBG50 and BBG100 I/R 24 h groups was reduced by 19, 33, 41 and 30 %, respectively. The density of P2X7-IR, NOS-IR, NF-IR and ChAT-IR neurons was reduced by 16, 56, 37 and 45 % in the I/R 14d saline group, respectively, and in the BBG50 and BBG100 I/R 14 days groups the densities was reduced by 3, 35, 27 and 21 %, respectively. This work indicates that I/R causes myenteric neuronal loss in I/R 0 h, saline 24 h and 14 days groups, and BBG treatment appeared to be effective in protecting neuronal class studied.

Poster #23 Cerebral blood ow in autonomic failure

L. Rivera Lara, P. Novak Department of Neurology, University of Massachusetts, MA, USA Background: Autonomic failure (AF), especially adrenergic, can be associated with orthostatic symptoms that are due cerebral hypoperfusion. Usually, the orthostatic blood pressure changes are used as a proxy for status of cerebral perfusion. However, the relationship between the cerebral blood ow velocity, that is more direct marker of cerebral perfusion and AF, is not well understood. Methods: 228 subjects, 136/92 women/men, mean age 53 years, sd 17.6 years, with orthostatic symptoms, and 40 healthy controls, underwent standardized autonomic testing (deep breathing, Valsalva maneuver, tilt test, QSART, skin biopsy). Cerebral blood ow velocity (CBv) from the left middle cerebral artery was monitored during the supine baseline and tilt using transcranial doppler. Composite autonomic

Poster #22 Photo-stimulating effects of low reactive level laser on bladder dysfunction in neurological disease rats
T. Uchiyama1,2, C. Yamaguchi1, T. Yamamoto2, R. Sakakibara3, M. Fuse1,4, M. Yanagisawa4, T. Kamai5, T. Ichikawa4, K. Hirata6, S. Kuwabara2, T. Yamanishi1

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Clin Auton Res (2012) 22:207258 severity score (CASS) has been used for grading AF into mild, moderate and severe. Results: Mild/moderate/severe AF was detected in 119/76/33 subjects. ANOVA showed signicant difference in mean CBv in graded AF, both in supine and tilt. The reduction of CBv was proportional to severity of AF, being the most abnormal in severe AF. There was also supine hypertension in severe AF. The drop of CBv during the tilt test was not signicant among all AF groups. The correlation between orthostatic hypotension and drop of the CBv during the tilt test was not signicant. Conclusion: CBv abnormalities are associated with AF. Baseline CBv is inversely proportional to degree of AF. The lowest baseline CBv was seen in severe AF group (in spite of supine hypertension in that group) indicating the presence of intracranial vasoconstriction. Chronic hypoperfusion can be associated with AF irrespectively of position of the body, e.g. supine or standing.

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Poster Session II Poster #25 Do the chronic heart failure patients have limited sympathetic response to a transient baroreex stress?
P. Zubin Maslov1, T. Breskovic1, J.K. Shoemaker2,3, Z. Dujic1 1 Department of Physiology, University of Split School of Medicine, Split, Croatia; 2Neurovascular Research Laboratory, School of Kinesiology, Western University, London, Ontario, Canada; 3 Department of Physiology and Pharmacology, Western University, London, Ontario, Canada Diastolic blood pressure (DBP) fall resulting from premature ventricular contraction (PVC) causes baroreceptor unloading and increase in the amplitude and duration of multi-unit sympathetic bursts suggesting an increase in axonal recruitment in that cardiac cycle. These larger bursts and their axonal content may reect the ability of the sympathetic nervous system to respond to hypotension. Chronic sympathetic hyperactivation characterizes heart failure (CHF) raising a question regarding the ability of these patients to further enhance sympathetic drive. We quantied the action potential (AP) content within multi-unit muscle sympathetic nerve activity (MSNA) from microneurographic recordings during sinus rhythm and during PVCs, quantifying the APs per burst and classifying these APs into clusters based on their peak-to-peak amplitude. Sympathetic neurograms were obtained from 4 moderate CHF patients, providing 188 sinus rhythmrelated bursts and 38 post-PVC bursts, and from two similarly aged control individuals, providing 129 sinus rhythm-related bursts and 36 post-PVC bursts. Compared to controls (10 3 APs/burst) the CHF group had higher AP content per burst during sinus rhythm (15 9 APs/burst P = 0.01) as well as higher number of active clusters per burst (4 1 vs. 3 1 clusters/burst, CHF patients vs. controls, respectively, P = 0.01). In both GROUPS, post-PVC bursts had higher AP frequency, number of APs, and number of active AP clusters (P = 0.05) compared with sinus-rhythm bursts. Our data indicate that despite their chronic sympathetic hyperactivity, CHF patients demonstrate the ability to enhance sympathetic outow further through increased number of APs/burst. The higher cluster number in the post-PVC bursts suggests CHF patients retain the ability to recruit additional, larger APs.

Poster #24 Added clinical value of cerebral blood ow in juveniles and young adults with neurocardiogenic syncope and dysautonomia as measured by near-infrared spectroscopy
J.E. Lankford, M.T. Numan, A. Gourishankar, I.J. Butler Department of Pediatric Neurology, Center for Dysautonomia, University of Texas at Houston Medical School, Houston, TX, USA Transcranial Doppler ultrasonography (TCD) has been utilized as a surrogate measure of cerebral blood ow with demonstrated impairments in cerebral blood ow in patients with orthostatic intolerance (OI). In our institution, near-infrared spectroscopy (NIRS) has been utilized as a method of measuring cerebral blood ow. During the period July 2010 to January 2012, we reviewed 71 adolescents and young adults diagnosed with neurocardiogenic syncope and dysautonomia who underwent bilateral cerebral perfusion monitoring with NIRS during head up tilt test (HUTT). Data was analyzed by visualization of contour changes in NIRS values. We used previously described phases of HUTT: dynamic tilt phase (early in tilt test), static phase (during tilt test), and post-tilt phase (return to supine). We found three variations in the dynamic tilt phase (gradual decrement, steep decline and no change), six variations in the static phase (constant throughout test, constant until onset of a steep decline, gradual decline throughout test, gradual decline until onset of a steep decline, waxing and waning throughout test, waxing and waning until onset of steep decline), and three variations in the post-tilt phase (mild, moderate, and severe overshoot). We also observed a distinction between the two cerebral hemispheres with respect to NIRS values during HUTT in 22 patients. Finally, 42 patients were unable to complete the HUTT (30 min duration) due to severe clinical postural intolerance. These results conrmed a decrease in cerebral blood ow as assessed by NIRS in patients with OI and autonomic dysfunction. Distinctly, we have proled the cerebral blood ow contours throughout the phases of HUTT and compared the values in both hemispheres. Discovery of such variations in cerebral blood ow may add insight into the clinical spectrum of this condition and physiological changes observed enable correlation with severity of postural intolerance.

Poster #26 Assessment of cardiovascular adrenergic function using the Valsalva maneuverreproducibility and validity of indices
T.L. Gehrking, J.A. Gehrking, J.D. Schmelzer, P.A. Low, W. Singer Department of Neurology, Mayo Clinic, Rochester, MN, USA Background: The Valsalva maneuver (VM) has a long tradition as integral component of standardized autonomic function testing. While heart rate responses to the VM provide information about cardiovagal integrity, blood pressure (BP) responses during certain phases of the maneuver provide valuable information about cardiovascular adren-

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242 ergic function. Various adrenergic indices derived from the VM have been described, but comparative assessment of their reproducibility and validity is lacking. We therefore sought to systematically evaluate previously described indices of cardiovascular adrenergic function derived from the VM in a cohort of subjects with graded adrenergic impairment. Methods: Using a large autonomic research database, we randomly selected three age-matched groups of 30 subjects: group one with severe adrenergic impairment dened as the presence of neurogenic orthostatic hypotension, group two with mild to moderate adrenergic impairment based on abnormal BP responses to the VM and/or borderline orthostatic BP drop, and group three consisting of healthy control subjects. Nine adrenergic indices were derived for each subject from two technically adequate VMs: BP drop and pulse pressure compression during early phase II, BP recovery during late phase II (calculated from baseline and from early phase II), BP overshoot during phase IV (magnitude and duration), BP recovery time (PRT), 50 % PRT, and a baroreex sensitivity index calculated from PRT. Reproducibility and validity of each parameter was assessed using correlation analysis and between group comparisons. Results: Signicant within parameter correlations were seen for all indices, but the most reproducible parameters were BP recovery during late phase II related to baseline, PRT, and BP drop during early phase II (Pearsons r = 0.910.96). The best separation of groups was achieved using BP recovery during late phase II (related to baseline and early phase II) as well as PRT (all perfect or near perfect separation between groups 1 and 3). BP drop and pulse pressure compression during early phase II and parameters related to phase IV overshoot showed the most overlap between groups. Conclusions: Parameters used to assess adrenergic function derived from the VM show considerable differences in reproducibility and validity. Superior parameters are those assessing late phase II BP recovery and PRT, while other parameters are less reproducible and/ or show greater overlap between normal and abnormal. Supported by NIH (NS44233, U54NS065736, K23NS075141, UL1RR24150) and Mayo Funds.

Clin Auton Res (2012) 22:207258 conductance were calculated as limb blood ow divided by MAP. MS elicited similar increases in MAP D10 1 vs. D11 1 mmHg), HR (D16 2 vs. D17 2 beats/min), FBF (D81 16 vs. D82 15 %) and FVC (D62 13 vs. D64 13 %) in men and women, respectively. In contrast, CBF (D16 8 vs. D42 8 %; p = 0.016) and CVC (D4 7 vs. D29 8 %; p = 0.012) responses to MS were exaggerated in women compared to men. Changes in FVC were signicantly correlated with changes in CVC in women (r = 0.674; p = 0.004), but not men. MSNA reactivity to MS tended to be augmented in men (D6 1 vs. D3 1 bursts/min; p = 0.11), and the changes in CVC were negatively correlated with increases of MSNA in men (r = -0.411; p = 0.045), but not women. In conclusion, our data suggest different patterns of calf vascular reactivity to MS in men and women that might relate, in part, to MSNA reactivity and/or altered vascular transduction of MSNA.

Poster #28 Melatonin does not alter skin sympathetic nerve response to mental stress
C.A. Ray, C.L. Sauder, M.D. Muller Penn State Heart & Vascular Institute, Penn State University College of Medicine, Hershey, PA, USA Melatonin attenuates muscle sympathetic nerve activity (MSNA) responses to sympathoexcitatory stimuli (e.g., orthostatic stress and otolithic stimulation). It is not known if melatonin has the same effect on skin sympathetic nerve activity (SSNA). Because melatonin has been reported to alter thermoregulation in which SSNA also contributes, it was hypothesized that melatonin would attenuate SSNA to a sympathoexcitatory stimulus. Therefore, the purpose of this study was to examine if melatonin alters SSNA responses to mental stress. Cognitive stress elicits marked increases in SSNA thus allowing us to observe potential attenuation in SSNA by melatonin. Nine young healthy subjects (6 men, 3 women) underwent experimental testing on two separate days. Three minutes of mental stress (i.e., mental arithmetic) were conducted before and after ingestion of melatonin (3 mg) or placebo. Participants were dressed in a water-perfused suit to maintain skin temperature at 35 C. Mental stress elicited comparable increases in mean arterial pressure (17 4 vs. 13 3 mmHg) and heart rate (28 6 vs. 25 5 beats/min) before and after melatonin ingestion. Both early (i.e., rst 10 s) and sustained (i.e., entire 3 min) responses for SSNA to mental stress were analyzed. Before ingestion of melatonin, mental stress elicited increases in SSNA within the rst 10 s (D218 24 %) and over the entire 3 min (D125 17 %). After ingestion of melatonin, SSNA responses were comparable in the rst 10 s (D203 16 %) and over the entire 3 min (D83 6 %). Mean skin temperature and sweat rate did not change with melatonin. Responses on the placebo day were not different between the two trials. In summary, unlike its effect on MSNA, melatonin did not alter SSNA responses to sympathoexcitation, as elicited by mental stress. This nding indicates that melatonin has contrasting effects on muscle and skin sympathetic nerve activity in humans. Supported by NIH (HL109952).

Poster #27 Sex differences in limb vascular reactivity to mental stress in humans
J.R. Carter1, H. Yang1, T.D. Drummer2 1 Department of Kinesiology and Integrative Physiology, Michigan Technological University, Houghton, MI, USA; 2Department of Mathematical Sciences, Michigan Technological University, Houghton, MI, USA Mental stress (MS) elicits a robust and consistent forearm vasodilation, but vascular reactivity in the calf remains inconsistent. MS has been reported to induce calf vasodilation more frequently in women (Butt et al., Clin Auto Res, 1999). Muscle sympathetic nerve activity (MSNA) is an important contributor to calf blood ow, yet the relations between sex, limb blood ow, and MSNA reactivity to MS have not been adequately explored. We hypothesized that MS would elicit more dramatic vasodilation of the calf in women, and that this might be explained by reduced MSNA reactivity and/or blunted sympathetic vascular transduction. We measured heart rate (HR), mean arterial pressure (MAP), calf blood ow (CBF), and forearm blood ow (FBF) in 18 men (age, 23 2 years) and 15 women (age, 22 1 years) during 5 min of supine baseline and 5 min of MS (serial subtraction). Calf (CVC) and forearm (FVC) vascular

Poster #29 The arterial baroreex resets with orthostasis

C.E. Schwartz, J.M. Stewart Department of Physiology, New York Medical College, Hawthorne, NY, USA

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Clin Auton Res (2012) 22:207258 The arterial baroreexes, located in the coronary sinus and along the arch of the aorta, are essential to the rapid short term autonomic regulation of blood pressure. In the past, they were believed to be inactivated during exercise because blood pressure, heart rate and sympathetic activity were so radically changed from their resting functional relationships with blood pressure. However, it was discovered that all relationships between coronary sinus pressure and either HR or sympathetic vasoconstriction maintained their curvilinear sigmoidal shape but were reset, or shifted, so as to best maintain BP during exercise. We examined the resetting of the arterial baroreexes during orthostasis comparing upright tilt with supine relationships between systolic BP and HR (the cardiovagal baroreex), mean BP and ventilation (the ventilatory baroreex) and diastolic BP and sympathetic nerve activity (the sympathetic baroreex). We used the modied Oxford method in which BP was rapidly varied with bolus injections of sodium nitroprusside followed 1 min later by phenylephrine. Both the cardiovagal and ventilatory baroreexes were reset with no change in gain or response range. In contrast, the sympathetic baroreex was augmented as well as shifted causing a similar increase in peripheral resistance that optimally defended the subject against hypotension. Increased peripheral resistance is not present in active skeletal muscles during exercise. This difference is likely selective for exercising muscle and may represent the actions of functional sympatholysis by which exercise metabolites interfere with adrenergic vasoconstriction.

243 -4.5 7.4 mmHg; Norm: -4.5 3.9 mmHg; Hypo:-5.2 5.5 mmHg; n = 8; P = 0.89). These preliminary results demonstrate a reduction in MSNA during PECO with suppression of the chemoreceptors, suggesting that the metaboreex sensitizes the chemoreex, and that the chemoreex may play a role in the integrated MSNA response to handgrip exercise.

Poster #31 Do multi-unit sympathetic discharge patterns change with age and cardiovascular disease?
D.N. Brewer1, P. Zubin Maslov2, Z. Dujic2, J.K. Shoemaker1 1 School of Kinesiology, Western University, London, Ontario, Canada; 2School of Medicine, University of Split, Split, Croatia Burst frequency in integrated muscle sympathetic nerve activity (MSNA) suggests increased sympathetic outow with age and cardiovascular disease (CVD). Assessment of burst frequency alone ignores the action potential (AP) content of each burst causing potential error in assessing sympathetic outow. This study tested the hypothesis that age and CVD increase MSNA by contrasting MSNA burst patterns of the integrated signal with AP content patterns. MSNA (microneurography) was recorded in Young, Older healthy, metabolic syndrome (MET), coronary artery disease (CAD) and congestive heart failure (CHF; Class II) (n = 7 per group) individuals. A signicant MANOVA, F(32,108) = 2.088, p \ 0.05, g2 = 0.9 suggested that variables of MSNA were different between groups. Univariate analysis using Tukeys HSD post hoc suggested that, compared with Young (17 6 b/min), burst frequency increased in Older (31 6), MET (34 10) and CAD (34 8) (P \ 0.001) and more in CHF (55 9 b/min; P \ 0.05 vs. all groups). APs per burst were similar across groups: young (11 6 APs/b), Older (7.7 2) and CHF (13 6) (NS; effect size = 0.92). Compared to Young (187 112 APs/min), APs per min were not different in Older (235 92), MET (305 103) or CAD (299 105) patients (NS) but increased to 746 367 APs/min in CHF (P \ 0.05 vs. all groups). Therefore, increased MSNA burst frequency with age or with moderate CVD disease or risk (CAD and MET) does not translate to more total AP discharge until severe cardiovascular disease (CHF) when a small increase in APs/burst compounds the elevated burst incidence to produce greater sympathetic outow. These results challenge the use of burst frequency alone as a discriminator between groups of varying age and health status. Supported by CIHR and NSERC funding.

Poster #30 Carotid chemoreex and muscle metaboreex interactions in humans

H. Edgell, M.K. Stickland Department of Medicine, University of Alberta, Edmonton, AB, Canada Both metaboreceptors and chemoreceptors play a role in the sympathetic response to exercise, and interactions between these reexes have been shown previously. The purpose of this study was to isolate the muscle metaboreex while stimulating/inhibiting the carotid chemoreceptor to better understand their interactions. Nine young healthy men (Height: 179.9 7.4 cm, Weight: 91.5 22.1 kg, Age: 24.0 3.7, VO2: 51.3 13.0 mL/kg/min) performed three trials of 40 % maximal voluntary contraction handgrip for 2 min, followed by 3 min of post-exercise circulatory occlusion (PECO). In random order, subjects either breathed room air, hypoxia (target SpO2 = 85 %), or hyperoxia (FIO2 = 1.0) during the PECO in order to modulate the chemoreex. Following these trials, a resting hypoxia trial was conducted without handgrip or PECO. Ventilation (VE), heart rate (HR), blood pressure (BP) and muscle sympathetic nervous activity (MSNA) data were continuously obtained. As expected, exercise increased all variables, and PECO in normoxia reduced all variables compared to exercise; however all except HR remained above baseline. Hyperoxia resulted in a greater reduction in MSNA during PECO as compared to both normoxia and hypoxia (Hyper: -18.0 6.2 bursts/min, Norm: -11.2 10.0 bursts/min, Hypo: -11.3 6.2 bursts/min; n = 6; P = 0.02). Hypoxia attenuated the reduction in HR during PECO as compared to both normoxia and hyperoxia (Hyper: -31.1 6.2 bpm, Norm: -26.6 7.2 bpm, Hypo: -3.8 7.1 bpm; n = 9; P \ 0.001), while there was a tendency for the reduction in VE during PECO to be less in hypoxia (Hyper: -4.9 6.8L/min; Norm: -3.8 2.9L/min; Hypo: +2.0 7.8L/min; n = 9; P = 0.08). There was no change in the reduction of BP during PECO with hyperoxia or hypoxia (Hyper:

Poster #32 Acute baroreex sensitivity impairment due to insulininduced experimental hypoglycemia
A. Rao2, I. Bonyhay1, S. Ballatori1, G. Adler2, R. Freeman1 1 Department of Neurology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA; 2Division of Endocrinology, Diabetes, and Hypertension, Brigham and Womens Hospital, Harvard Medical School, Boston, MA, USA Background: In our previous studies, we demonstrated that baroreex sensitivity (BRS) was impaired 16 h after antecedent hypoglycemia.

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244 However, it is not known when this BRS impairment begins after the exposure of hypoglycemia and whether other acute hemodynamic changes occur with the baroreex change. Objective: To test the hypothesis that BRS impairment occurs during the hypoglycemia exposure. Methods: Hyperinsulinemic hypoglycemic clamp studies were performed in 15 healthy study participants (age 25 5 years, BMI: 23 4; 12 men) not taking any medications. The night before study procedures, study participants were admitted to the Clinical Research Center at Brigham and Womens Hospital and were asked to fast and remain supine after midnight. Hypoglycemic clamps were performed in the morning with insulin (80 mU/m2 body surface area/min) infused for 150 min. Dextrose (20 %) was infused to maintain glucose levels at 50 mg/dL for 120 min. Modied Oxford baroreex tests were performed in duplicate immediately before initiating the clamp (euglycemia) and during the nal 30 min of hypoglycemia: a bolus injection of 100 lg sodium nitroprusside (vasodilator) was administered, followed 60 s later by a bolus injection of 150 lg phenylephrine hydrochloride (vasoconstrictor). The sequential administration of these agents produces a drop followed by a rise in blood pressure over a short time course. Changes in autonomic measures, blood pressure response and baroreex sensitivity (BRS), were analyzed by repeated measures ANOVA. Results: Blood pressure prior to each modied Oxford was not different between euglycemic (E) and hypoglycemic (H) states (MAP: E: 86 4 vs. H: 84 5 mmHg), whereas heart rate signicantly increased during hypoglycemia (E: 58 6 vs. H: 71 8 bpm, P \ 0.001). Blood pressure response to phenylephrine was signicantly blunted during hypoglycemia (E: 32 15 vs. H: 20 9 mmHg, P \ 0.01), which was also accompanied by a signicant decrease in BRS (E: 36 16 vs. H: 19 8 ms/mmHg, P \ 0.005). Conclusion: The present study demonstrates that hypoglycemia acutely decreases BRS, suggesting ongoing hypoglycemia reduces vagal control of the heart. These ndings could have clinical implications in patients experiencing ongoing hypoglycemia.

Clin Auton Res (2012) 22:207258 BP selectively by reducing autonomic function because it decreased BP by only 15 4 mmHg in a control group of patients with pure autonomic failure and severe supine hypertension. Baseline REE was higher in obese Hispanics than in lean Hispanics (1,836 128 vs. 1,321 37 kcal/d; P \ 0.01), but the difference disappeared after adjusting for fat-free mass (FFM). Furthermore, the fall in REE adjusted for FFM after trimethaphan was similar in both groups (lean -59 15 vs. obese -54 22 kcal/day adjusted by FFM; p [ 0.05). Compared to obese Hispanics, obese Caucasians had similar baseline and intrinsic BP and REE, which fell by a magnitude similar to that of obese Hispanics with trimethaphan. In conclusion, sympathetic activation induced by obesity is an important factor of BP elevation in both obese Hispanics and Caucasians, but does not contribute to the increase in REE.

Poster #34 The impact of injury to autonomic pathways on cardiovascular disease risk after spinal cord injury
H.J.C. Ravensbergen1,2, I.S. Sahota1,2, S.A. Lear1,3, V.E. Claydon1,2 1 Department of Biomedical Physiology and Kinesiology, Simon Fraser University, Burnaby, British Columbia, Canada; 2International Collaboration On Repair Discoveries, Department of Medicine, University of British Columbia (ICORD), Vancouver, British Columbia, Canada; 3Faculty of Health Sciences, Simon Fraser University, Burnaby, British Columbia. Introduction: The leading cause of morbidity and mortality in individuals with spinal cord injury (SCI) is cardiovascular disease. The mechanisms underlying the high risk of cardiovascular disease after SCI are unclear. Leading a sedentary lifestyle after SCI has been proposed to be the main contributing factor. However, we propose that direct injury to cardiovascular autonomic pathways plays an important role. We, therefore, aimed to compare risk factors for cardiovascular disease between individuals with autonomically complete SCI, autonomically incomplete SCI, and able-bodied controls. Methods: Completeness of injury to cardiovascular autonomic pathways was determined by level of injury (above T5), low plasma noradrenaline, and decreased power of low frequency oscillations in systolic blood pressure. Classic cardiovascular risk factors were evaluated (glucose tolerance, insulin sensitivity, fasting lipid proles and measures of obesity). Physical activity was determined using questionnaires. We tested 19 able-bodied controls, and 29 individuals with SCI (13 autonomically complete and 16 autonomically incomplete). Results: Glucose tolerance and insulin sensitivity were impaired only in the autonomically complete SCI group. HDL cholesterol and the HDL/total cholesterol ratio were lower in both SCI groups compared to controls. We did not nd any differences in LDL cholesterol between groups. Physical activity scores were similar in all groups. Severity of impairment in glucose tolerance was positively correlated with severity of autonomic injury. Conclusion: These results are compatible with an independent relationship between autonomic dysfunction after SCI and impaired glucose handling. Impairments in lipid proles were observed in both SCI groups. These ndings support the need to target treatment towards autonomic dysfunction after SCI, in addition to lifestyle modication, in order to reduce morbidity and mortality due to cardiovascular disease.

Poster #33 Autonomic contribution to blood pressure and resting energy expenditure in obese hispanics
L.E. Okamoto, C. Shibao, A. Gamboa, A. Diedrich, G. Farley, S. Paranjape, I. Biaggioni Department of Medicine, Division of Clinical Pharmacology, Vanderbilt University, Nashville, TN, USA Compared to Caucasians, obese Hispanics are at higher risk for diabetes and metabolic syndrome but have lower prevalence of hypertension, suggesting different mechanisms of obesity hypertension. To assess the autonomic contribution to blood pressure (BP) and resting energy expenditure (REE), we induced autonomic withdrawal with the ganglionic blocker trimethaphan in 10 lean (BMI 23.8 0.5 kg/m2, 33 3 years.) and 9 obese (BMI 35.1 1.2 kg/ m2, 42 3 years.) mestizo Hispanics, and 7 obese (BMI 35.4 0.9 kg/m2, 37 3 years.) Caucasians. Baseline supine systolic BP was higher in obese Hispanics compared to lean Hispanics (116 5 vs. 96 2 mmHg; P \ 0.01). After autonomic blockade, systolic BP fell more in obese Hispanics compared to lean Hispanics (-25 5 vs. -3 3 mmHg; P \ 0.01), and the intrinsic BP in the absence of autonomic inuences was similar between the two groups (93 5 vs. 93 3 mmHg; P [ 0.05). Trimethaphan lowered

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245 increased central arterial stiffness could be implicated in the etiology of hypertension. Sedentary AA women have been shown to have signicantly higher levels of autonomic dysfunction, signicantly lower levels of BRS and signicantly higher levels of arterial stiffness versus their Caucasian (C) counterparts. Regular physical activity by individuals at high risk for developing hypertension has been shown to reduce the rise in blood pressure that occurs over time. Aim: To determine if there are differences in BRS, autonomic function and central arterial stiffness between very active AA women and matched C women. Materials and methods: We compared 8 very active AA women to 17 age, height, weight and blood pressure matched C women. Autonomic modulation and BRS were assessed using spectral density analysis and transfer function analysis of the electrocardiogram and beat-tobeat blood pressure. Central arterial stiffness was determined via pulse wave velocity. Results: No signicant differences existed between groups in BRS (AA = 19.6 4.6 vs. C = 16.4 10.7 ms/mmHg, p = 0.4); sympathetic vasomotor activity (LFSBP) (AA = 3.6 2.0 vs. C = 3.8 2.0 mmHg2, p = 0.8); parasympathetic nervous activity (HFln) (AA = 7.3 + 1.0 vs. 7.3 1.2 ms2, p = 0.90) or central arterial stiffness (AA = 5.6 + 0.90 vs. C = 5.5 1.2 m/s, p = 0.80). Discussion: These ndings are suggestive that very active AA women may not be at higher risk for developing hypertension versus their C counterparts. Conclusions: BRS, autonomic function and central arterial stiffness is similar in very active AA and C women.

Poster #35 What is the best marker for obesity in individuals with spinal cord injury?
H.J.C. Ravensbergen1,2, M.C. Keenleyside1, S.A. Lear1,3, V.E. Claydon1,2 1 Department of Biomedical Physiology and Kinesiology, Simon Fraser University, Burnaby, British Columbia, Canada; 2International Collaboration on Repair Discoveries (ICORD), Vancouver, British Columbia, Canada; 3Faculty of Health Sciences, Simon Fraser University, Burnaby, British Columbia Cardiovascular disease is now the leading cause of morbidity and mortality in individuals with spinal cord injury (SCI). Obesity is well known to be a major predictor for cardiovascular disease risk. A simple and widely used marker for obesity in the able-bodied population is body mass index (BMI), but it has some major limitations. In the SCI population, current cut-off values for BMI lead to an underestimation of obesity, probably because BMI is not sensitive to the altered contributions of fat and fat free mass to body weight after SCI. As such, improved measures of obesity that are more accurate in this population are needed. We aimed to identify the best marker of obesity after SCI, considering both practically of use, and ability to detect adiposity and cardiovascular disease risk. We measured BMI, waist circumference (WC), waist-to-hip ratio (WHR), waist-to-height ratio (WHtR) and neck circumference (NC) as known markers of obesity. We investigated relationships between these measures and total body and abdominal fat percentages as measured using dual energy X-ray absorptiometry. We also determined correlations between the obesity markers and a cardiovascular disease risk score incorporating fasting levels of glucose, insulin, triglycerides, ratio of total cholesterol to high density lipoprotein (HDL) cholesterol (TC/ HDL) and glucose 120 min after an oral glucose load. Measurements were conducted in 30 individuals with SCI. We identied signicant correlations between WC, WHR and WHtR and fat percentages, individual risk parameters, and the sum of risk score, indicating these are strong markers for obesity and cardiovascular risk after SCI. Importantly, each of these markers is easy to measure in this population, unlike BMI which requires a wheelchair scale to determine body weight. We propose that these measures could provide simple but more sensitive alternatives to BMI that are easy to use in general medical practice or at home.

Poster #37 Impaired autonomic modulation in acute stroke improves with clinical recovery within 72 hours
M.J. Hilz1,2, H. Marthol1, S. Moeller1, J. Koehn1, A. Akhundova1, P. De Fina3, S. Schwab1 1 Department of Neurology, University of Erlangen-Nuremberg, Erlangen, Germany; 2Departments of Neurology, Medicine, and Psychiatry, New York University, New York, NY, USA; 3 International Brain Research Foundation, Flanders, NJ, USA Background and aim: In acute stroke, there is compromised cardiovascular autonomic modulation (CAM) that correlates with stroke severity as assessed by the National Institutes of Health Stroke Scale (NIHSS) (Hilz MJ, et al. Stroke. 2011). Autonomic dysfunction has not yet been correlated with clinical changes in stroke severity during the initial 72 h after stroke-onset. We therefore assessed CAM and baroreex sensitivity (BRS) within the rst 24 h and after 72 h upon stroke-onset. Methods: In 48 patients with middle cerebral artery ischemic stroke (24 women, 68 14 years), we assessed NIHSS-scores and CAM parameters within 24 and 72 h after stroke-onset. From 5 min RRinterval (RRI) and blood pressure (BP) recordings, we calculated spectral powers of RRI oscillations in mainly sympathetically mediated low- (LF: 0.040.15 Hz) and parasympathetically mediated highfrequency (HF: 0.150.5 Hz) ranges, and BRS as gain between systolic BP- and RRI-oscillations for coherence [0.7. We compared cardiovascular parameters of both measurements using t tests and NIHSS-scores using the Wilcoxon-test (signicance: p \ 0.05). Results: From the rst to the second assessment, there was a decrease in NIHSS-scores [median (inter-quartile range): 5 (411) vs. 3 (110)], systolic and diastolic BPs, and increase in RRI-LF-powers, RRI-HF-powers and BRS [5.4 5.3 vs. 9.4 6.6 ms mmHg-1].

Poster #36 Central arterial stiffness and autonomic modulation in active women
P. Latchman1, G. Gates2, J. Pereira1, R. Axtell1, M. Bartels3, R. De Meersman4 1 Southern Connecticut State University, New Haven, CT, USA; 2The Children Hospital at Monteore, Bronx, NY, USA; 3Columbia University Medical Center, Columbia University, New York, NY, USA; 4Alfaisal University, College of Medicine, Riyadh, Saudi Arabia Introduction: Hypertension is one of the most common health problems in the United States. Of any group in the United States, African American (AA) women have the greatest propensity for hypertension. Loss of baroreex sensitivity (BRS), autonomic dysfunction and

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246 Conclusion: After 72 h, decrease in NIHSS scores and increase in LFand HF-RRI-modulation and in BRS show an association between CAM recovery and clinical stroke improvement. Acknowledgement: The study was supported by Bayer Healthcare Pharmaceuticals, Germany, the Rolf- and Hubertine-SchiffbauerFoundation, Hof, Germany, and the International Brain Research Foundation Inc., USA.

Clin Auton Res (2012) 22:207258 Atrial brillation (AF) deteriorates the prognosis in patients with chronic heart failure (CHF). Probably it is due to peculiarities of hemodynamic control. The goal was to evaluate the neural peculiarities of vascular control and orthostatic tolerance in patients suffering both AF and CHF. Patients and methods: The study included totally 61 patients with CHF II-IV NYHA class, with ejection fraction (EF) 35.0 10.1 %, including 25 ones having AF and 36 persons with sinus rhythm (SR). According to clinical and nosological characteristics, both groups were comparable. In addition to general clinical surveys, several special investigations were performed: 1tilt-test, 2forearm blood ow (FBF) by occlusion plethysmography to Dohn as well as its dynamics during cold stress (CS), 3cardiopulmonary baroreex testing (CPBR) when creating a vacuum in the lower part of the body -10 mm Hg, and 4to assess the metaboreex hand-grip test was executed. Hemodynamic parameters were recorded by using a continuous non-invasive BP monitor Finometer-PRO, (FMS, Amsterdam). Results: Patients with AF were older: 60.1 9.0 and 54.5 8.0 years, p \ 0.05 and had a larger left atrial volume index: 69.8 23.7 and 54.2 15.6 sm3/m2, p \ 0.05. Sizes of the other cavities of the heart and contractility were not different. Patients with AF had higher total peripheral vascular resistance (TPR): 1.34 0.42 and 1.00 0.30 MU, p \ 0.005 and lower FBF: 3.1 1.5 and 4.8 2.4 ml/100 sm3 min., P \ 0.05, between which observed an inverse correlation: r = -0.34, p \ 0.05. The reaction in response to sympatho-activation tests was also different: an increase in diastolic blood pressure (DBP) during hand-grip test in patients with AF was greater, 14.9 5.9 and 11.1 5.9, p \ 0.05, whereas the vasoconstriction in response to CS: 0.24 0.14 and 0.31 0.13, p \ 0.05 and reduced venous return (CPBR): 0.16 0.17 and 0.29 0.11 rel.units., p \ 0.05were lower. In addition, in patients with AF was more frequently observed decrease in DBP in the standing position: -2.1 5.2 mm Hg, whereas in the SR- its natural growth: 2.0 6.3 mm Hg, p \ 0.05, and the dynamics of DBP in orthostasis was directly related to the initial TPR: r = 0.43, p \ 0.001 and CPBR, r = -0.49, p \ 0.001. Conclusion: In patients with CHF simultaneously suffering AF a more pronounced increase in vascular tone related with a reduction of peripheral blood ow, as well as enhanced metaboreex. It is accompanied with weakening of vasomotor reactivity to cold stress and reducing venous return that is connected with diminishing of tolerance to orthostasis.

Poster #38 Relation of cardiovagal baroreex sensitivity to impaired carotid artery elastic function in patients with tetralogy of Fallot
A. Pinter, T. Horvath, A. Sarkozi, D. Cseh, M. Kollai Semmelweis University, Institute of Human Physiology and Clinical Experimental Research, Budapest, Hungary Sudden cardiac death (SCD) is a common late complication in patients with tetralogy of Fallot (ToF). Reduced cardiovagal baroreex sensitivity (BRS) was found to be an independent predictor of SCD. Reduced BRS was reported in ToF patients, but the underlying mechanism is not clear. Our laboratory has shown earlier that BRS is related to carotid artery distensibility (DC) in healthy subjects and that DC is reduced in ToF. Considering all above, we aimed to test the hypothesis that reduced BRS is related to impaired carotid artery elastic function. We studied 36 ToF patients (21 11 years) and 50 age- and gender-matched healthy control subjects. Carotid artery diastolic diameter and pulsatile distension was determined by echo wall tracking and carotid blood pressure was measured by tonometry. DC was calculated subsequently. Spontaneous blood pressure uctuations coupled with adequate heart rate responses were used to calculate spontaneous BRS (sBRS). Intravenous phenylephrineinduced blood pressure elevation followed by heart rate reduction was used to determine BRSphe. Results: (mean SD) BRS indices were markedly reduced in patients compared with controls (sBRS 9.3 9.2 vs. 17.5 6.8 ms/ mmHg; BRSphe 16.8 10.2 vs. 32.6 11.4 ms/mmHg). DC also showed signicant difference between groups (5.1 1.8 vs. 6.8 2.8 9 10-3/mmHg). DC correlated signicantly and positively with BRS across patients and control subjects as well (sBRS r = 0.49 vs. r = 0.42*; BRSphe r = 0.31 vs. r = 0.73*). Multiple regression analysis indicated that DC is an independent determinant of BRS indices in ToF patients. (p \ 0.05; *p \ 0.01) Our data demonstrate that reduced DC can contribute to impairment of BRS in ToF patients. Lifestyle modications, such as moderate aerobic exercise, sodium restriction and omega-3-fatty acid intake, appear to be efcient interventions in preventing and treating carotid artery stiffness andindirectlyimpaired baroreex function.

Poster #40 Calcitonin gene related peptide level and endocannabinoid system activity in patients with abdominal obesity and arterial hypertension
E. Shlyakhto, E. Bazhenova, O. Belyaeva, A. Berezina, O. Berkovich, E. Baranova Department of Cardiology, Almazov Federal Centre of Heart, Blood and Endocrinology, Saint-Petersburg, Russian Federation Hypothesis: Calcitonin gene-related peptide (CGRP)vasoactive neuropeptide implicated in physiological processes. Endocannabinoid system activates in patients with abdominal obesity (AO) and arterial hypertension (AH) and stimulates CGRP release in experiments. Aim: To evaluate serum CGRP and plasma endocannabinoid (ECs) levels (anandamide (AEA) and 2-arachidonoylglycerol (2-AG)) in obese patients with AH.

Poster #39 Features of vascular neurogenic regulation in patients with atrial brillation and heart failure
O.V. Mamontov, A.V. Kozlenok, E.R. Bernhard, E.V. Parmon, E.V. Shlyakhto Almazov Federal Heart, Blood and Endocrinology Centre, Saint-Petersburg, Russian Federation

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Clin Auton Res (2012) 22:207258 Materials and methods: We examined 56 patients (42.0 0.8 years old) with AO (IDF, 2005) and 24 non-obese (NO) subjects. 50 % of obese patients had AH. Level of CGRP was evaluated by EIA method (Peninsula Laboratories, LLC, USA), levels of ECsby chromatomass-spectrometry. Results. CGRP level didnt differ in patients with AO (n = 31) and NO-subjects (n = 12) (0.26 0.04 ng/ml and 0.18 0.03 ng/ml; p [ 0.05), and in obese patients with AH and obese patients without AH (0.30 0.07 ng/ml and 0.21 0.07 ng/ml; p [ 0.05). AEA and 2-arachidonoylglycerol 2-AG levels were higher in obese patients (n = 24) versus NO-subjects (n = 20)AEA: 16.0 2.2 ng/ml and 7.1 1.1 ng/ml; p \ 0.0001; 2-AG: 0.9 0.1 ng/ml and 0.5 0.1 ng/ml; p = 0.005. AEA level were higher in patients with AO and AH versus patients with AO and without AH (0.9 0.1 ng/ ml and 0.6 s0.1 ng/ml; p = 0.002). 2-AG level didnt differ in patients with AO and AH and patients with AO and without AH (16.5 3.3 ng/ml and 10.0 1.6 ng/ml; p [ 0.05). We revealed correlations between AEA level and duration of obesity (DO) (r = 0.6; p = 0.02), BMI (r = 0.6; p = 0.0001), waist circumference (WS) (r = 0.6; p = 0.0001), systolic blood pressure (SBP) (r = 0.5; p = 0.001) and diastolic BP (DBP) (r = 0.5; p = 0.001). We revealed correlations between 2-AG level and DO (r = 0.5; p = 0.001), BMI (r = 0.4; p = 0.002), WS (r = 0.4; p = 0.004), SBP (r = 0.3; p = 0.004) and DBP (r = 0.3; p = 0.005). We didnt nd correlations between CGRP level and all investigating parameters. Conclusions: We didnt nd changes of CGRP level in obese hypertensive patients. ECs levels associated with DO, antropometric parameters, blood pressure in patients with AO and AH.

247 and higher BFnu and hs-CRP (0.65 0.18 and 0.50 0.68) than CAD- (RMSSD = 30.73 15.93; SDNN = 37.66 15.65; AFnu = 0.44 0.19; BFnu = 0.55 0.19; LF/HF = 1.78 1.60; hsCRP = 0.26 0.33). Conclusion: These results indicate that autonomic heart dysfunction and inammation are related with progression of CAD.

Poster #42 Oligober recordings detail single-ber sympathetic nerve discharge

C.-K. Su 1, C.-H. Chiang1,2, C.-M. Ho2, C.-M. Lee1,3, Y.-P. Fan1 1 Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan; 2 Department of Anesthesiology, Taipei Veterans General Hospital and National Yang-Ming University, Taipei, Taiwan; 3Department of Molecular & Cell Biology, University of California at Berkeley, Berkeley, CA, USA Whole-bundle nerve recording is an easy technique to gauge central sympathetic outow. However, this conventional technique fails to detail individual ber activities. Aiming for a signal resolution at the single-ber level, we established a novel experimental model socalled oligober recordings. In vitro splanchnic sympathetic nervethoracic spinal cord preparations were obtained from SpragueDawley neonatal rats. Whole-bundle nerves were incubated in a glass micropipette containing 0.5 % collagenase for 90 min. The dissociated nerve fascicles were then brought into a small caliber micropipette for electrical signal recordings. Oligober activities that displayed several distinct spike potential waveforms were often achieved. Automation of spike sorting was primarily based on spike waveform features using a series of custom-made LabVIEW programs incorporated with MATLAB scripts. Data clusters were automatically selected by j-means clustering algorithms followed by verication of the waveform homogeneity by principal component analysis (PCA). Dissimilar waveforms unselected by PCA were retrieved by a subtraction algorithm (SA), which partially resolved overlapped spikes. Both PCA-selected and SA-retrieved spikes were combined as unit activities. To evaluate if unit activities truly originated from single bers, we examined the probability distribution of interspike intervals (ISIs) and determined if a change of waveform features was a function of their preceding ISIs. 77 unit activities collected from 30 experiments were conrmed as single-ber activities. Using the oligober recording techniques, we could simultaneously examine, on average, *3 single ber activities per experiment. After some modications, these techniques should be applicable to any peripheral nerve recordings.

Poster #41 Heart rate variability and high sensitivity C-reactive protein: inuence of coronary artery lesions
N.Y. Tamburus1, V.C. Kunz1, R.F.L. Paula2, M.R. Salviati2, T.A.G. Nery2, E. da Silva1,2 1 Department of Physiotherapy, Laboratory of Cardiovascular o Carlos, Sa o Carlos, Sa o Physiotherapy, Federal University of Sa Paulo, Brazil; 2Department of Physiotherapy, College of Health o Paulo, Sciences, Methodist University of Piracicaba, Piracicaba, Sa Brazil Introduction: High level of C-reactive protein and decreased HRV (heart rate variability) are considered important indicators of systemic inammation and autonomic dysfunction, both have been associated with risk of coronary artery disease (CAD). However, it is unknown the relationship of HRV indexes and high sensitivity C-reactive protein (hs-CRP) with progression of CAD. Objective: The aim of the study was to evaluate and compare plasma levels of hs-CRP and HRV indexes in patients with only coronary risk factors for CAD and with coronary artery disease. Methods: A sample of 163 men (mean age 56.54 6.87 years) was divided into two groups: CAD group (obstructive CAD C 50 % DAC+ n = 87) and coronary risk factor group, without signicant obstruction (DAC- n = 76). Heart rate (HR) and R-Ri was measured using a PolarS810i for 15 min in supine rest. The HRV analysis was performed using frequency (high [HF] and low frequencies [LF] normalizes units; LF/HF ratio) and time domain (RMSSD and SDNNms). The hs-CRP was determined by nephelometry. Statistical analysis: MannWhitney test, with level of signicance = 5 %. Results: The CAD + presented lower RMSSD, SDNN and AFnu values (14.12 7.04, 21.63 9.67 and 0.34 0.18, respectively)

Poster #43 Cardiovascular autonomic control in the rst year after spinal cord injury
J. Inskip1,2, M. McGrath, B. Kwon2,3, V. Claydon1,2 1 Department of Biomedical Physiology and Kinesiology, Simon Fraser University, Burnaby, BC, Canada; 2International Collaboration on Repair Discoveries (ICORD), Vancouver BC, Canada; 3Combined Neurosurgical and Orthopaedic Spine Program, Department of Orthopaedics, University of British Columbia, Vancouver, Canada

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248 Autonomic pathways that travel in the spinal cord are susceptible to spinal cord injury (SCI) and their disruption can result in a range of cardiovascular dysfunctions. The development and evolution of these complications remains poorly understood. Here we sought to evaluate cardiovascular function in the rst year after traumatic SCI using spectral analyses. Resting supine beat-to-beat blood pressure and 3-lead electrocardiography were recorded during supine rest for 15 min at several time points in the rst year post-injury. Here we present results from recordings performed in the rst 2 weeks postinjury, and again at 1 year, on the same eight subjects: four with cervical SCI and four with low thoracic or lumbar SCI. Autonomic function was quantied using spectral analysis of heart rate variability (HRV) and blood pressure variability (BPV). Individuals also completed a questionnaire at each visit evaluating symptoms of cardiovascular dysfunction after SCI. All subjects showed increased total HRV at 1 year post-injury compared to the rst time point. Our initial BPV analyses show two different patterns. Individuals with low level lesions show frequency domain analyses that are essentially normal and do not show signicant changes over time post-injury. Individuals with cervical SCI show evidence of impaired cardiovascular autonomic function that spontaneously improves over time. It remains to be determined whether this reects autonomically complete lesions that recover, or incomplete lesions with altered autonomic function associated with the initial trauma. The early period after SCI appears to be a time when autonomic control of the cardiovascular system can change signicantly. Clinically, it may be wise to assess the cardiovascular system at several stages in the rst year after injury in order to get a clearer picture of the level of cardiovascular autonomic control.

Clin Auton Res (2012) 22:207258 analogous to other thermodynamic systems not all energy transfers cause changes in RRI. In some instances heat production that does not result in meaningful work appears to dominate. Therefore, changes in RRI cannot be predicted or derived solely from isolated descriptors of cardiac autonomic activity without simultaneously considering overall effective energy transfer.

Poster #45 The autonomic testing of normal subjects

G. Chelimsky1, S.M. Ialacci2, T.C. Chelimsky1 1 Medical College of Wisconsin, Milwaukee, WI, USA; 2Case Western Reserve University, Cleveland, OH USA Background: The prevalence of abnormalities in autonomic testing (ANS) in the general healthy population is unknown. Hypothesis: Syncope can occur in a healthy population, but other orthostatic syndromes and neuropathy are usually not present. Methods: IRB prospective study evaluating results of autonomic testing in healthy female [18 years who were well screened for diseases known to be associated with autonomic abnormalities, had BMI \ 35, not pregnant or breast feeding and no recent history of surgeries. The subject underwent a detailed neurological and tender point examination for bromyalgia. Exclusion included: pin sensation \8 in hands and/or feet, C8 sites rated C4/10 for bromyalgia, have history of pelvic pain, psychological state is unstable, pregnancy or breastfeeding. All subjects underwent autonomic testing including: cardiac response to deep breathing (DB), cardiac response to Valsalva maneuver (VM), 70 head up tilt test (TTT) for 30 min and sudomotor axon reex (QSART). Results: 14 females were enrolled (mean 31 years, 2055 years), BMI of 22.9 3.3. DB was normal in all subjects. 1 had decreased VM. None reported any orthostatic symptoms during TTT. One subject had a heart rate increase of 35 from baseline in the rst 10 min (age 24) and 5 had a heart rate increase of 3242 bpm from baseline after 10 min. One subject had a syncopal episode without postural tachycardia or orthostatic hypotension. In QSART, 9/13 had decreased or absent sweating in the forearm. 6 had decreased or absent QSART in C2 locations. Conclusion: Healthy females may have an asymptomatic heart rate increase during tilt and demonstrate abnormal QSARTs, particularly in the forearm and abnormal sudomotor function in the absence of other abnormalities. Supported by NIH grant R01DK083535

Poster #44 Sympathovagal balancea thermodynamic perspective

R. Schondorf1, J. Benoit1, M.J. Latte2 1 Department of Neurology, Jewish General Hospital, McGill University, Montreal, QC, Canada; 2DyAnsys, Geneva, Switzerland We have previously applied a novel time domain method to provide kinematic descriptors of vagal and sympathetic responses of cardiac autonomic activity during well-characterized physiologic maneuvers. This method essentially considers each component in isolation and provides little insight into the overall impact of these responses. Thermodynamics considers energy changes within a system in terms of heat entering the system and macroscopic work done by the system. Usually the latter is regarded as meaningful by an outside observer. We adapted our analytic method to obtain an index of energy balance from the original phase space representation of our beat-to-beat responses. We have found that the directionality and magnitude of our index coheres well with expected changes in RR intervals (RRI) in normal subjects at rest, during head-up tilt (HUT) and during dynamic neck suction and in patients with POTS during HUT and following MAST pants ination. Conversely, patients following cardiac transplantation manifest little modication in RRI despite signicant changes in energy transfer. During neurally mediated syncope (NMS) an intermediate condition is observed. During supine and early HUT, changes in energy translate as changes in RRI. However, in the minutes prior to syncope there is a transition to a state where even large swings in energy are essentially ineffective at changing RRI. Finally, at syncope there is an abrupt change in responsivity once again to a large directionally appropriate energy change with resultant bradycardia. It would appear therefore that

Poster #46 Alpha-adrenergic blockade unmasks a greater compensatory vasodilation in hypoperfused contracting muscle
D.P. Casey, M.J. Joyner Department of Anesthesiology, Mayo Clinic, Rochester, MN, USA We previously demonstrated that acute hypoperfusion in exercising human muscle causes an immediate increase in vascular resistance that is followed by a partial restoration (\100 % recovery) of ow. In the current study, we examined the contribution of a-adrenergic vasoconstriction in the initial changes in vascular resistance at the

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Clin Auton Res (2012) 22:207258 onset of hypoperfusion as well as in the recovery of ow over time. Nine healthy male subjects (29 2) performed rhythmic forearm exercise (20 % of maximum) during hypoperfusion evoked by intraarterial balloon ination. Each trial included: baseline, exercise prior to ination, exercise with ination, and exercise after deation (3 min each). Forearm blood ow (FBF; ultrasound), local (brachial artery), and systemic arterial pressure (MAP; Finometer) were measured. The exercise bout was repeated during phentolamine infusion (a-adrenergic receptor blockade). Forearm vascular conductance (FVC; ml min-1 100 mmHg-1) and resistance (mmHg ml min-1) was calculated from BF (ml min-1) and local MAP (mmHg). Recovery of FBF and FVC (steady state ination plus exercise value nadir)/ [steady state exercise (control) value-nadir] with phentolamine was enhanced compared with the respective control (no drug) trial (FBF = 97 5 % vs. 81 6 %, P \ 0.05; FVC = 126 9 % vs. 91 5 %, P \ 0.01). However, the absolute (0.05 0.01 vs. 0.06 0.01 mmHg ml min-1; P = 0.17) and relative (35 5 % vs. 31 2 %; P = 0.41) increase in vascular resistance at the onset of balloon ination was not different between the a-adrenergic receptor inhibition and control (no drug) trials. Therefore, our data indicate that a-adrenergic mediated vasoconstriction restricts compensatory vasodilation during forearm exercise with hypoperfusion, but is not responsible for the initial increase in vascular resistance at the onset of hypoperfusion.

249 simplied scoring algorithm, and is suitable for widespread use in autonomic research and practice.

Poster #48 Autonomic, blood ow and sensory small ber scale (ABSS)
P. Novak Department of Neurology, University of Massachusetts, Worcester, MA, USA Background: There is a need for objective, fully quantitative and clinically relevant instrument for scoring of autonomic, cerebral blood ow and sensory small ber domains. The only available clinically validated scale is Composite Autonomic Severity Score (CASS) that scores autonomic functions. The objective of this study was to validate a new scaleAutonomic, Cerebral Blood Flow and Sensory Small Fiber Scale (ABSS). Methods: ABSS is based on CASS and denes the following domains: (1) Cardiovagal; (2) Heart rate at rest and tilt; (3) Adrenergic; (4) Sudomotor; (5) Sensory and (6) Intracranial blood ow. Cardiovagal domain uses deep breathing test only. Heart rate domain uses heart rate at supine and tilt test. Adrenergic domain has 3 separate subdomains: adrenergic failure -Valsalva maneuver, adrenergic failure-tilt, adrenergic hyperactivity-tilt. Sudomotor domain has 2 subdomains: functional (identical to CASS) and morphological (using sweat glands nerve ber density). Sensory domain uses epidermal nerve ber density (ENFD). The intracranial blood ow (CBf) domain uses blood ow velocity from the middle cerebral artery obtained during supine period, tilt test and Valsalva maneuver. ABSS was validated prospectively in 545 subjects with the following diagnoses: diabetes (53), Parkinson disease (63), autonomic neuropathy (389), healthy controls (40). CASS has been used as a gold standard for grading of autonomic failure (AF) into mild, moderate and severe. Results: ANOVA showed overall signicance in ABSS scores among diagnostic groups as well as graded AF. ENFD and CBf also correlated with diagnostic groups and graded AF. Specicities and sensitivities were above 90 % is separation of normal from abnormal responses. ABSS classied 12 % of subjects as having adrenergic failure that were classied as having normal response using CASS. Conclusion: ABSS is compatible with CASS in both separations of diagnostic groups as well as in grading of AF. ABSS is more sensitive to detect adrenergic failure, it is able to detect autonomic overactivity, provides expanded dynamic range, and denes new domains.

Poster #47 COMPASS 31a rened and abbreviated composite autonomic symptom score
D.M. Sletten1, G.A. Suarez1, P.A. Low1, J. Mandrekar2, W. Singer1 1 Department of Neurology, Mayo Clinic, Rochester, MN, USA; 2 Biomedical Statistics and Informatics, Mayo Clinic, Rochester, MN, USA Objectives: The autonomic symptom prole (ASP) is a well-established questionnaire evaluating severity and distribution of autonomic symptoms. Using a subset of questions, we have generated a validated scoring instrument, the composite autonomic symptom score (COMPASS). An error-prone scoring algorithm, time-consuming administration, and lack of internal consistency necessitated a redesign to an updated, more concise, statistically solid, and broadly applicable tool for autonomic symptom quantication. Methods: We assessed the internal consistency of COMPASS using Cronbach alpha coefcients based on the ASP of 405 healthy control subjects. Applying a simplied scoring algorithm, we then used exploratory factor analysis with orthogonal rotation and Eigenvalue calculations to extract internally consistent domains and to reduce dimensionality. This was followed by expert revisions to eliminate redundant content and to retain clinically important questions, and nal assessment of the new instrument. Results: The new, simplied scoring algorithm alone resulted in higher Cronbach alpha values in all domains. Factor analysis revealed 7 domains with a total of 54 questions retained. Expert revisions resulted in further reduction of questions and domains with a remaining total of 31 questions in 6 domains (COMPASS 31). Measures of internal consistency were much improved compared to COMPASS. Following appropriate weighting, this instrument provides an autonomic symptom score from 0 to 100. Conclusions: COMPASS 31 is a rened, internally consistent, and markedly abbreviated quantitative measure of autonomic symptoms. It is based on the original ASP and COMPASS, applies a much

Poster #49 Systemic dysautonomia in complex regional pain syndromea feasibility study
mali1, K. McNeeley1, L. Zhou2, T. Chelimsky3 K.R. Che 1 Department of Neurology, Sentara-EVMS, Norfolk, VA, USA; 2 Department of Neurology, Mount Sinai School of Medicine, New York, NY, USA; 3Department of Neurology, Medical College of Wisconsin, Milwaukee, WI, USA Objectives: To assess the autonomic nervous system (ANS) in CRPS at the affected limb and other sites.

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250 Background: CRPS is thought to be perpetuated by somatic-autonomic coupling. Some reports suggested a cardiovascular dysautonomia in CRPS, raising the possibility that CRPS is a local manifestation of a widespread disorder of the ANS. In this study, we assessed the ANS at the pupil, the cardiovascular and sudomotor systems. Methods: 5 patients with CRPS type I of a lower limb, with no systemic symptoms of dysautonomia underwent pupillometry, heart rate variability to deep breathing (HRDB), Valsalva maneuver (VM), tilt table (HUT), QSART and skin biopsy (SB). Results: a. Pupillometry: One patient displayed relative loss of sympathetic tone, and the second showed abnormalities in both sympathetic and parasympathetic parameters. A 3rd patient displayed equivocal ndings. b. HRDB: 1 patient showed decreased HR variability, suggesting cardiac parasympathetic abnormality. c. VM: Valsalva ratios and blood pressures were normal in all patients. d. HUT: none of the patients displayed abnormalities. e. QSART: 2 patients showed sudomotor abnormalities at the affected foot and 1 patient showed abnormalities at both the affected and unaffected feet. f. Skin biopsy: 4 patients showed reduction of somatic and sudomotor small bers at the site of maximal allodynia and 1 patient showed a reduction of these bers in both limbs. Conclusions: a. Skin biopsy remains the most sensitive test in conrming the diagnosis of CRPS b. A mild degree of subclinical dysautonomia far from the affected limb seems to be present in some patients with CRPS. The exact percentage of patients who have a generalized dysautonomia cannot be concluded based on this small sample. However, this study is feasible and a larger sample of patients is necessary.

Clin Auton Res (2012) 22:207258 Eight salivary melatonin samples were obtained between 7 and 11 PM and analyzed using ELISA. Results: Core body and skin temperature above the SCI gradually decreased from 7 to 11 PM in all groups with no statistically interaction between the 3 groups. Skin temperature below the SCI in tetraplegics signicantly increased, whilst controls and paraplegics demonstrated a gradual decline. A statistically signicant and comparable increase in melatonin levels from 7 to 11 PM was observed in controls (2.59 1.0410.62 4.59 pg/ml) and paraplegics (4.28 3.2813.10 7.39 pg/ml), whilst tetraplegics demonstrated a small decrease (5.25 3.722.41 1.25 pg/ml). In controls and paraplegics, we found moderate correlations between melatonin levels and core body temperature (r = 0.44 (P = 0.01) and r = 0.54 (P = 0.01), respectively), whilst no statistically signicant correlation was evident in tetraplegics. Conclusion: We found a strong relation between the increase in melatonin levels and decline in core body temperature during the evening hours in controls and paraplegics, whilst such relation was not present in tetraplegics. A potential explanation may relate to the skin temperature, as the decline in lower limbs skin temperature during evening hours in controls and paraplegics was not present in tetraplegics.

Poster #51 Post-exercise recovery period in patients with idiopathic ventricular arrhythmias
E. Parmon, T. Tulintseva, E. Berngardt, E. Panova, E. Shlaykto Almazov Federal Heart, Blood and Endocrinology Centre, Saint Petersburg, Russian Federation

Poster Session III Poster #50 Thermophysiological consequences of an absent evening melatonin release in spinal cord injury
H. Jones1, J.T. Groothuis2,3), T.M.H. Eijsvogels2, J. Nyakayiru2, R.J.M. Verheggen2, A. Thompson1, E.J.W. van Someren4, G. Atkinson1, M.T.E. Hopman2, D.H.J. Thijssen 1,2 1 Research Institute for Sport and Exercise Science, Liverpool John Moores University, Liverpool, United Kingdom; 2Department of Physiology, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands; 3Department of Rehabilitation, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands; 4 Department of Sleep and Cognition, Netherlands Institute for Neuroscience, Amsterdam, The Netherlands Background: Individuals with a spinal cord injury (SCI), especially tetraplegics, experience poor sleep quality. Recently, we demonstrated that, in tetraplegia, there is an absence of evening release of melatonin and altered circadian rhythmicity of core body temperature. Melatonin is an important hormone for the initiation of sleep, possibly via thermoregulatory changes. Here, we examine the core and skin thermoregulatory consequences of alterations in melatonin release in SCI individuals. Methods: Between 7 and 11 PM, we examined core body temperature (telemetry system), skin temperature above and below the SCI (temperature sensors) in 15 SCI individuals (AIS A), 9 paraplegic and 6 tetraplegic, and 10 age- and gender matched able-bodied controls. A delayed decline of recovery heart rate (HRR) has been associated with autonomic dysfunction. Appearance of ventricular arrhythmia (VA) also often depends on autonomic nervous system modulation. Objective: to examine HR and VA in the recovery period (RP) in patients with idiopathic VA. Materials and Methods: the study enrolled 30 patients (14 men; mean age 38.2 4.1 years old) with idiopathic VA, control group consisted of 32 healthy persons (16 men, 36.2 1.6 years old). Structural cardiac pathology was excluded. Done Holter ECG. Exercise training test (ETT) was performed according to standard Bruce protocol, without any therapy, till to submaximal HR (85 % or more). The HR and the quantity of VA at the 1, 2, 3 and 5 min of RP were studied. Results: Holter ECG showed mean 9722.5 single VE (sVE) daily, predominantly day-long type. In the control group there was no VA. During the ETT there were no signicant differences between patients and control groups (p [ 0.05): the pre-test HR was 84.3 15 and 86.7 7.3 bpm, resp.; HRmax = 159.4 13.1 and 177.9 3.9 bpm with 10.5 2.5 and 12.5 0.9 METS, resp. In RP the most decline HRR was at 1 min (HRR1) = 22.4 7.6 and 28.2 8.2 bpm, resp. (p \ 0.05). HRR2 min = 17.3 2.1 and 23.6 4.1 bpm, resp.(P \ 0.05). HRR3 min = 11.2 3.4 and 12.1 5.2 bpm, resp. (p [ 0.05). The pre-test number of sVEmean 6.3 sVE/min, at peak test3.3, at 1 min4.3, at 2 min5.1, at 3 min4.3, at 5 min4.7 sVE/min. The HRR1 had negative correlation to amount VE of the third minute of recovery (r = -0.52, p \ 0.05). Conclusions: HRR index was normal (more then 12 bpm). Most likely, there is an evidence of the deceleration of parasympathetic activation and/or the increasing of sympathetic activity. It is accompanied by decrease in HR speed restoration and increasing activity of ventricular ectopic center to the 3rd minute of RP. Further investigation is needed.

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251 Pediatric Neurology Clinic. All underwent a 6 h neuropsychological evaluation utilizing well-standardized measures of cognitive and emotional functioning: WISC-IV/WAISIV, WRAML-2, Conners CPT-II, and Clinical Assessment of Depression. Results: One patient had an antecedent H1N1 infection, and no etiology was found in 5. Four patients were not in a formal school setting secondary to their cognitive symptoms. All patients reported signicant difculty concentrating. All but one endorsed signicant problems with processing speed or brain fog. Two complained of excessive fatigue and one reported anxiety. Clinically reported symptoms of poor concentration and difculty processing information differed dramatically from the patients performance on standardized measures of sustained attention, processing speed, and memory. Despite the fact that many were not attending school due to clinically reported symptoms of inattention and brain fog, all patients scores on measures of processing speed, attention, working memory, and verbal memory were within the Average to Above Average range. Conclusions: While adolescents with POTS often endorse debilitating cognitive and psychiatric symptoms, formal testing reveals no neuropsychological decits. This preliminary nding indicates the necessity of further study to elucidate the bases for this disparity. Investigations looking at parental and adolescents reactions to the diagnosis of POTS and assessment of the relationships between medical symptoms, parenting style, and pre-morbid emotional functioning seem warranted.

Poster #52 Regulation of circulation during exercise in adolescents with postural orthostatic tachycardia syndrome (POTS)
A. Goodloe, D. Soma, C.K. Brands, P.R. Fischer, P.T. Pianosi Department of Pediatric and Adolescent Medicine, Mayo Clinic, Rochester, MN, USA Introduction: We have shown that adolescents with the constellation of symptoms comprising fatigue, nausea, pain (usually headache), and dizziness, with or without syncope, have relative tachycardia during exercise. While high heart rates (HR) are expected with deconditioning, we observed unexpected changes in blood pressure and cardiac output as well. Methods: We reviewed records of adolescents presenting with longstanding history of any mix of aforementioned symptoms, who underwent both head-up tilt (HUT) and symptom-limited maximal cardiopulmonary exercise (CPEX) testing from Jan 2010 to April 2012. Those with POTS had C40 bpm rise in HR with HUT. Cardiac output (Q) was measured by inert gas rebreathing at rest and at 23 levels of light-moderate exercise. Results: 277 patients between 9 and 19 years of age (78 % female) underwent both HUT and CPEX. Cardiac output (Q) rose with exercise on average 6 L/min per L/min rise in oxygen uptake (VO2) for the group as a whole. 87 patients met denition of POTS. The Q-VO2 relationships among patients with this group was bimodal, with breakpoint at *7.5 L/min per L/min increase of VO2. The slope of the Q-VO2 relationship averaged 5.2 1.1 versus 9.0 1.3 in the normal (N = 65) and high output (N = 32) subgroups of POTS patients, respectively. The change in mean arterial blood pressure from rest to exercise was blunted in normal vs high output POTS subgroups. HR change with HUT did not vary between these subgroups (48 9.5 versus 50.5 10 bpm, p = 0.167). None of these patients was anemic. Conclusions: A sub-group of adolescents with POTS who demonstrate a hyperdynamic circulation during exercise also have a blunted blood pressure response to exercise. We speculate this group of patients has failure of normal regional vasoconstriction required during dynamic exercise and must greatly increase ow through an inappropriately dilated systemic circulation to maintain perfusion pressure.

Poster #54 How important is the T in POTS using pediatric versus adult diagnostic criteria for postural tachycardia?
I.T. Jarjour, A.M. Hernandez, L.K. Jarjour Department of Pediatrics, Baylor College of Medicine, Houston, TX, USA Objective: To evaluate whether children who meet adult but not pediatric criteria (J Pediatr 2012; 60:222) for POTS represent a similar clinical phenotype. Background: Published reports of pediatric POTS have used adult values of heart rate increment (HRinc) or absolute HR (HRabs). However, normative pediatric data point to higher HR cut off values than adults. Methods: We reviewed the records of 64 patients evaluated between April 2007 and March 2011 for probable POTS by standing or headup tilt test (HUT) or both at a Tertiary Pediatric Neurology Clinic. POTS-pc (pediatric criteria) was dened as frequent, 2 or more symptoms of OI for [3 months and HRinc of C40 or HRabs C 120 bpm ages 1419 and HRabs C 130 ages 813 years. Diagnosis of POTS-ac-only (adult criteria) used HRinc of C30 bpm or HRabs C 120 bpm regardless of age, within 10 min of active standing or HUT, without arterial hypotension. Data are presented as mean SD. Results: 32 patients had POTS-pc (81 % female; age 15 1.8 years), with mean duration of symptoms of 1.8 years. Pre-existing conditions included ADHD (19 %), anxiety (22 %), and depression (16 %). Symptoms included chronic fatigue (81 %), sweating disorder (59 %), sleep disorder (57 %), nausea (58 %), abdominal pain (39 %), vomiting (26 %), weight loss (35 %), brain fog (32 %), and migraine (31 %). Quantitative sudomotor axon testing was abnormal in 14 of 25 patients (56 %), abnormal GI motility with gastroparesis in 5/24 (21 %), and slow gastric emptying in 7/10 (70 %). There were

Poster #53 Neuropsychological proles in adolescents with postural tachycardia syndrome (POTS)
K.D. Evankovich, L.K. Jarjour, A.M. Hernandez, I.T. Jarjour Department of Pediatrics, Baylor College of Medicine, Houston, TX, USA Objective: POTS is associated with complaints of cognitive symptoms, brain fog, and anxiety that may contribute to severe functional disability. To date, there are no published data on neuropsychological proles of pediatric patients with POTS. Methods: We reviewed the medical records and neuropsychological data of 6 adolescents with frequent symptoms of orthostatic intolerance for [3 months and increased HR of C40 or HR of C120 bpm minutes within 10 min of active standing or head-up tilt test (HUT), who were evaluated between 10/2008 and 8/2010 at a tertiary care

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252 30 patients with POTS-ac-only who had the same clinical phenotype as the POTS-pc group without any signicant differences in prevalence of age, sex, duration of symptoms, pre-existing conditions, symptoms, test results, or outcome data. Conclusions: Children and adolescents with POTS diagnosed using newly proposed pediatric criteria have a similar phenotype to those who only meet adult criteria. We propose a diagnosis of probable POTS for the latter group.

Clin Auton Res (2012) 22:207258 Objective: To assess autonomic function and epidermal nerve ber density in patients with postural tachycardia and evidence of a small ber neuropathy based on laboratory and/or clinical evaluation. Background: The Postural Tachycardia Syndrome (POTS) comprises a heterogeneous group of patients who have in common excessive orthostatic tachycardia and symptoms of orthostatic intolerance. Evidence of a limited autonomic neuropathy is not infrequently encountered in these patients and has lead to the designation of a neuropathic subtype of POTS. On the other hand, denitions of POTS typically exclude the presence of more widespread autonomic failure and secondary causes of postural tachycardia, although these cases may represent the continuation of a spectrum of limited autonomic neuropathies with an orthostatic tachycardia phenotype, and may provide helpful information towards a better understanding of neuropathic POTS. Design/Methods: 11 patients were recruited with evidence of (1) orthostatic tachycardia (HR increment C30 bpm) and (2) the presence of a small ber neuropathy (abnormal QSART at the foot or at least two other sites, or clinical symptoms consistent with small ber neuropathy). Secondary neuropathic causes of orthostatic tachycardia were specically not excluded. These patients were compared to 11 healthy control subjects. All participants underwent standardized autonomic reex testing and a CASS score was obtained. Punch skin biopsies were performed at the distal and proximal leg. After staining with PGP9.5, the number of intraepidermal bers/mm (IENFD) was quantied by one observer blinded to site and clinical status. Results: 2 patients had orthostatic tachycardia in the setting of a more widespread idiopathic autonomic neuropathy, 1 patient had autonomic neuropathy in the setting of CIDP, 7 patients had POTS with abnormalities on QSART, and 1 patient had POTS with normal QSART but distal sensory symptoms. Both patients with idiopathic autonomic neuropathy had markedly abnormal sudomotor function; only one of them had abnormal IENFD, but signicant morphologic abnormalities (ber tortuosity and swelling, patchy ber distribution) were noted in the other patient. The patient with CIDP had absent sudomotor responses and absent IENFD at all tested sites. The seven patients with POTS and abnormalities on QSART had all normal IENFD but two (29 %) had signicant morphologic abnormalities (ber segmentation and swelling). The patient with POTS and distal sensory symptoms had normal QSART and normal IENFD. Conclusions: Neuropathic POTS comprises a limited neuropathy with almost exclusive involvement of autonomic bers, while involvement of somatic bers is seen in a number of patients with secondary causes of orthostatic tachycardia and more widespread autonomic neuropathies. The ndings support the hypothesis of neuropathic POTS as part of a spectrum of autonomic disorders resulting in orthostatic tachycardia with mild, selective autonomic neuropathy on one side and widespread autonomic and somatic ber loss on the other side of the spectrum. Supported by NIH (NS32352, U54NS065736, K23NS075141, UL1RR24150) and Mayo Funds.

Poster #55 Palpitations in postural tachycardia syndrome: what do they tell?

R.K. Khurana Department of Medicine, Medstar Union Memorial Hospital, Baltimore, MD, USA Introduction: In patients with postural tachycardia syndrome, multiplicity and severity of symptoms exceeds demonstrable organic pathology, favoring the hypothesis of hypochondriasis. To test this hypothesis, we used the somatosensory amplication scale (SSAS), a validated 10-item questionnaire for the assessment of hypochondriasis, and palpitations (heart beat perception), a psychophysiological variable that could be quantitatively manipulated. Methods: Participants 21, 10 normals compared to 11 patients. All participants rated each of the 10 items of the SSAS scale from 0 to 4. All were asked to select the quality (pounding, thumping, heart beating in the neck, racing, skipping, stopping, uttering, heart beating irregularly) of palpitations at supine rest and in response to tachycardia produced by two sympathetic stimuli (Valsalva maneuver [VM] and 10 min head-up tilt [HUT]) and one vagolytic stimulus (atropine administration, 0.03 mg/kg body weight I.V.). Data were compared using a t test. Results: Total SSAS scores (mean SEM): normals 14.4 2.3, patients 17.45 1.5, p = 0.27. Palpitations: There were no differences between palpitations at rest or following atropine administration. However, patients had a higher response after VM (81.8 % vs. 10 %, p = 0.001) and with HUT (63.6 % vs. 0 %, p = 0.002). Quality of palpitations was better discriminated by patients compared to normals despite identical stimuli. For example, one patient felt uttering at rest, pounding with VM, racing with HUT, and heart beating in the neck with atropine. Conclusions: Insignicant overall increase in SSAS scores militated against somatosensory amplication and hypochondriasis. Palpitations are mediated by sympathetic excitation and not vagal withdrawal. The ability of patients to discriminate the quality of palpitations in response to individual stimuli suggests visceral sensitization, possibly of cortical origin. Psychophysiologic or pharmacologic management of this phenomenon may be of symptomatic benet.

Poster #57 Origins of cognitive dysfunction in postural tachycardia syndrome

A.C. Arnold1, K. Haman2, E.M. Garland1, S.Y. Paranjape1, C.A. Shibao1, I. Biaggioni1, D. Robertson1, S.R. Raj1 1 Division of Clinical Pharmacology, Vanderbilt University School of Medicine, Nashville, TN, USA; 2Department of Psychiatry, Vanderbilt University School of Medicine, Nashville, TN, USA

Poster #56 The spectrum of neuropathic orthostatic tachycardia

W. Singer, T.L. Gehrking, P.A. Low Department of Neurology, Mayo Clinic, Rochester, MN, USA

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Clin Auton Res (2012) 22:207258 Background: Postural tachycardia syndrome [POTS] is a disabling condition characterized by excessive tachycardia upon standing, in the absence of blood pressure changes. Although the underlying pathophysiology remains unclear, upright posture produces numerous symptoms in POTS including profound impairments in cognitive function. However, the nature of these cognitive impairments has not been fully described. Thus, we tested the hypothesis that POTS patients will exhibit greater abnormalities on neuropsychiatric testing relative to controls. Methods and Results: A series of validated neuropsychiatric tests were administered to 23 POTS patients and 21 age-, gender- and intelligence-matched healthy subjects [HS] in seated and standing positions. Orthostatic heart rate increases were greater in POTS (34 11 vs. 17 9 bpm; p \ 0.01), with no differences in pressure. Attention and cognitive processing speed were reduced in seated POTS patients (Ruff 2&7 t-scores: POTS 40 9 vs. HS 49 8; p \ 0.01; Symbol Digit Modalities Test t-scores: POTS 45 12 vs. HS 51 8; p \ 0.01), despite similar psychomotor speed between groups. Measures of executive functioning were also lower in seated POTS patients suggesting difculties in tracking, mental exibility and set-shifting (Trails B: POTS 46 8 vs. HS 52 8; p \ 0.01; Stroop Word-Color, POTS 45 10 vs. HS 56 8; p \ 0.001). While groups did not differ in seated memory performance, logical memory task scores were signicantly decreased in POTS upon standing (Randt short story immediate recall: POTS 10 4 vs. healthy 13 3; delayed recall: POTS 8 4 vs. healthy 11 4; p \ 0.01). There were no differences in measures of verbal uency, associative memory or working memory between groups in either posture. Conclusions: These ndings suggest global decits in attention and executive processing, even when POTS patients are seated. Impairments in standing semantic memory were also evident, which may contribute to postural cognitive dysfunction. Further studies are needed to localize specic brain regions of pathology in order to develop treatments for cognitive dysfunction in POTS.

253 pressure, and cardiac stroke volume (impedance cardiography) in the supine position and during graded head-up tilt. Results: Compared with placebo, ivabradine had no effect on supine heart rate, blood pressure, or cardiac stroke volume, while metoprolol decreased supine heart rate (p \ 0.001) and blood pressure (p \ 0.001). On reboxetine + placebo, upright heart rate was 113 bpm (95 % CI 104123). Compared with placebo, ivabradine and metoprolol reduced upright heart rate 12 (95 % CI 421, p \ 0.006) and 21 (95 % CI 1330, p \ 0.0001) bpm, respectively. The decrease in stroke volume during head-up tilt was similar between treatment groups. However, stroke volume and cardiac output at a given heart rate were decreased with metoprolol, but not with ivabradine. Orthostatic tolerancemeasured as the time to (pre)syncope during head-up tiltwas not affected by either treatment. Conclusion: Short-term pharmacological I(f) inhibition with maximal recommended ivabradine doses ameliorates hyperadrenergic orthostatic tachycardia elicited by NET inhibition, albeit to a lesser extent than beta1-adrenergic blockade. At a given heart rate, beta1-adrenergic blockade but not I(f) inhibition decreased cardiac stroke volume and cardiac output. Funded by Deutsche Forschungsgemeinschaft.

Poster #59 Cardiovascular autonomic response to nitric oxide inhibition in POTS patients
I. Bonyhay, C. Gibbons, A. Benson, R. Freeman Department of Neurology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA Background: Earlier reports associate alterations in nitric oxide (NO) availability with POTS. Studies of cutaneous microcirculation suggest decreased NO availability in non-neuropathic POTS, whereas NO availability is increased or normal in neuropathic POTS patients. Studies of NO synthase (NOS) polymorphisms also suggest that NO may play a role in the development of POTS. Despite these reports, it is not known whether NO abnormalities are merely a biological marker or they also have clinical signicance. Objective: To investigate the role played by NO in cardiovascular autonomic control in POTS. Methods: In a double-blind, placebo-controlled study, NO inhibition was performed in 24 POTS patients (20F, 4M, 32 9 years) and 10 healthy control subjects (7F, 3M, 28 7 years). Placebo and NO inhibition were administered in randomized order on two consecutive days. Nitric oxide inhibition was achieved by a 15-min loading dose of 5 mg/kg NG-Monomethyl-L-Arginine (L-NMMA) infusion, followed by a maintenance dose of 50 lg/kg/min L-NMMA infusion throughout the study. The form of placebo administration was identical with that of L-NMMA. Deep breathing, random breathing, modied Oxford baroreex test and tilt-table test were performed during the study. Changes in autonomic measures such as heart rate variation with breathing, baroreex sensitivity (BRS) and hemodynamic response to tilt test during placebo and NO inhibition were analyzed by repeated measures ANOVA and unpaired t-test within and between subjects. Patients and controls were also classied as neuropathic or non-neuropathic based on IENFD using skin biopsy, quantitative sensory testing and QDIRT. Results: Baseline blood pressure was not different between POTS patients and controls (SBP: 113 9 vs. 112 15 mmHg; DBP: 69 6 vs. 68 5 mmHg), while baseline heart rate was higher in POTS patients compared to controls (68 12 vs. 59 10 bpm, P \ 0.01). Patients with neuropathic POTS had higher resting heart

Poster #58 Pharmacological I(f) pacemaker current inhibition in a human postural tachycardia syndrome (POTS) model
C. Schroeder1, K. Heusser1, D. Rieck2, F.C. Luft3, J. Tank1, J. Jordan1 1 Institute of Clinical Pharmacology, Hannover Medical School, Hannover, Germany; 2Institute for Biometry, Hannover Medical School, Hannover, Germany; 3Experimental Clinical Research , Berlin, Germany Center, Medical University Charite Background: POTS is characterized by excessive cardiac sympathetic drive during orthostatic stress. The condition can be mimicked in healthy subjects through pharmacological norepinephrine reuptake transporter (NET) inhibition. The nal pathway mediating the tachycardia at the level of the sinus node is beta-adrenoceptor stimulation and subsequent I(f) pacemaker current modulation. Aim: To compare hemodynamic responses to placebo, I(f)-blockade, and beta1-adrenergic blockade in a human POTS model. Methods: We included 19 healthy men in a three-way double-blind, randomized, and crossover trial. Subjects ingested ivabradine (7.5 mg), metoprolol (95 mg), or matching placebo 13 and 1 h before testing. Additionally, subjects ingested the selective NET inhibitor reboxetine (4 mg) on all 3 occasions. We measured heart rate, blood

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254 rates and blood pressures compared to non-neuropathic POTS and healthy control subjects (P \ 0.05). Conclusion: Baseline characteristics were similar between POTS subjects and control subjects, with the exception of resting and tilted heart rate. Additional baseline differences were noted between subtypes of neuropathic and non-neuropathic POTS. The effects of NO inhibition on POTS will be reported at the AAS meeting after study unblinding.

Clin Auton Res (2012) 22:207258 from adipocytes. To test the hypothesis that sympathetic activation is associated with the increase in IL-6 and CRP, we measured these inammatory markers in 44 lean (29 2 years., BMI 22.6 0.4) and 16 overweight or obese (37 2 years., BMI 29.6 0.9) female patients with postural tachycardia syndrome (POTS), a condition characterized by increased sympathetic tone, and in 26 lean (29 3 years., BMI 22.6 0.4) and 19 overweight or obese (45 2 years., BMI 35.3 1.5) female healthy controls. Compared to lean controls, lean POTS, overweight POTS and overweight controls had greater sympathetic activity measured by low-frequency variability of blood pressure (LFSBP, 3.1 0.3 vs. 5.6 0.6, 7.2 1.3, and 7.9 0.7 mmHg2, respectively, P \ 0.01), lower parasympathetic tone measured by high-frequency heart rate variability (HFRRI, 1,441 356 vs. 381 65, 425 120 and 440 129 ms2, respectively, P \ 0.01 for lean POTS vs. lean controls), and increased serum levels of IL-6 (2.3 0.4 vs. 4.1 0.5, 4.9 0.9 and 3.9 0.4 pg/mL, respectively, P \ 0.01). CRP, on the other hand, was increased only in the overweight groups (4.9 1.7 and 3.8 1.0 for overweight POTS and overweight controls) but not in the lean groups (0.8 0.2 and 0.9 0.2 mg/L for lean POTS and lean controls, P \ 0.01 for the differences between groups). IL-6 was very low in 3 patients with dopamine-b-hydroxylase deciency and congenital absence of norepinephrine (1.1 0.3 pg/mL), consistent with sympathetic modulation of this cytokine. We conclude that sympathetic activation and parasympathetic withdrawal are associated with increased serum IL-6 levels in POTS patients and controls with excess weight. The coupling between IL-6 and CRP, however, requires increased adiposity. These results suggest a non-adipocyte origin of IL-6 in POTS.

Poster #60 Postural tachycardia syndrome: optimal duration of diagnostic orthostatic challenge
W.B. Plash, V. Nwazue, A. Diedrich, I. Biaggioni, E.M. Garland, S.Y. Paranjape, B.K. Black, W.D. Dupont, C. Shibao, S.R. Raj Autonomic Dysfunction Center, Division of Clinical Pharmacology, Vanderbilt University School of Medicine, Nashville, TN, USA Objectives: Postural tachycardia syndrome (POTS) is characterized by a heart rate increase (dHR) C30 beats per min (bpm) within 10 min of upright posture with orthostatic symptoms. However, many POTS patients show signicant increases in heart rate with a 1 min stand. If POTS diagnostic testing could be performed in \10 min, clinical efciency could be signicantly increased. We hypothesized POTS patients would meet the 30 bpm dHR criterion in \10 min. Methods: Patients with POTS (n = 14, 12F, 37 3 years) and healthy subjects (n = 15, 13F, 34 2 years) underwent both a 608 tilt table test (TILT) and a stand test (STAND) for 10 min each. dHR was assessed at 1 min intervals for TILT and at 1, 3, 5, and 10 min for STAND. Data was used to generate the sensitivity (SN) and specicity (SP) at each time point for dHR C30 bpm. Results: For TILT, SN increased and SP decreased from 1 min (SN = 64 %, SP = 93 %) to 3 min (SN = 100 %, SP = 73 %), when all POTS patients achieved the 30 bpm criterion. SP continued to decrease over time, and SP = 40 % at 10 min. With STAND, SN increased but SP decreased from 1 min (SN = 56 %, SP = 73 %) to 10 min (SN = 100 %, SP = 67 %). SN for STAND did not reach 100 % until 10 min. Conclusions: All POTS patients achieved the 30 bpm criterion within 3 min of TILT, and TILT beyond 3 min decreased specicity. In contrast, 100 % sensitivity was not achieved with STAND before 10 min. Diagnostic tilt table testing for POTS can be truncated to 3 min without a decrease in sensitivity. This shorter test could allow for increased clinic efciency and cost effectiveness, without sacricing patient care by missing the POTS diagnosis.

Poster #62 Blood pressure effect of droxidopa in hypotensive individuals with spinal cord injury
J. Wecht, D. Rosado-Rivera, C. Yen, M. Radulovic, W. Bauman Center of Excellence for the Medical Consequences of SCI, James J Peters VA Medical Center, Bronx, NY, USA In 1992, Muneta and colleagues reported the clinical utility of droxidopa to treat hypotension in a 72-year-old female with a T4 spinal cord injury (SCI). In combination with a high sodium diet, droxidopa (600 mg) reduced the fall in blood pressure (BP) during seated postures. To date, the BP effect of droxidopa has not been reported in a sample of individuals with SCI. Therefore, we sought to determine the BP effect of escalating dose of droxidopa (100, 200 and 400 mg) during 3 laboratory visits in hypotensive subjects with SCI. Nine individuals with SCI participated. The level of SCI ranged from cervical to low thoracic (C3 to T10) lesions; all were chronically injured (214 years) and non-ambulatory; 8 were motor complete (AIS A & B). Subjects were hypotensive at baseline (BL: systolic BP: 86 15 mmHg; diastolic BP: 52 9 mmHg); BL BP did not differ among the 3 visits. Upon supine repositioning prior to drug administration, BP increased signicantly (systolic BP: 101 13 mmHg; diastolic BP: 62 7 mmHg; p \ 0.0001 vs. seated BL); droxidopa did not augment this positional increase in BP (systolic BP: 100 23 mmHg; diastolic BP: 62 16 mmHg). Seated BP was signicantly increased from BL after droxidopa in a dose-dependent manner (100 mg: 94 15/61 8 mmHg; 200 mg: 98 14/ 62 8 mmHg; 400 mg: 108 12/68 9 mmHg; p \ 0.0001). Although the average elevation in seated BP was relatively modest, mean BP remained signicantly increased above BL values for 4 h after droxidopa administration (systolic BP: 94 16 mmHg,

Poster #61 Uncoupling of serum interleukin-6 and C-reactive protein in lean patients with postural tachycardia syndrome
L.E. Okamoto, S.R. Raj, A. Gamboa, C. Shibao, A.C. Arnold, A. Diedrich, G. Farley, I. Biaggioni Department of Medicine, Division of Clinical Pharmacology, Vanderbilt University, Nashville, TN, USA Circulating plasma C-reactive protein (CRP) is elevated in obesity, induced in part by increased secretion of interleukin-6 (IL-6) derived

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Clin Auton Res (2012) 22:207258 p \ 0.01; diastolic BP: 61 10 mmHg, p \ 0.0001). These preliminary data suggest that low to moderate doses of droxidopa do not worsen supine increases in BP in persons with SCI. Although droxidopa increased seated BP in a dose-dependent manner, subjects remained relatively hypotensive. Question remains as to the effective dose of droxidopa that normalizes BP in this population.

255 orthostatic hypotension. The aim of this study was to examine the effect of the combination ergotamine and caffeine on blood pressure and pre-syncopal symptoms on standing in a group of patients with autonomic failure. A total of 12 patients participated in this study. Eight were men and the average age was 64 10 years. The combination ergotamine and caffeine increased seated SBP by 19 mm Hg compared with placebo (95 % CI: -2 to 40 mm Hg, P = 0.07) and reduced the orthostatic symptom score by 9 points (95 % CI: 0.916, P = 0.03), compared with baseline. In conclusion, the combination ergotamine and caffeine could be an alternative therapy for orthostatic hypotension in patients with autonomic failure.

Poster #63 Prevalence of orthostatic hypotension in asymptomatic veterans

Poster #65
J. Wecht, C. Yen, S. Pena, A. Ivan, W. Bauman Center of Excellence for the Medical Consequences of SCI, James J Peters VA Medical Center, Bronx, NY, USA Orthostatic hypotension (OH), dened as a fall in systolic blood pressure (SBP) C20 mmHg and/or a fall in diastolic blood pressure (DBP) C10 mmHg within 3 min of assuming an upright position, is associated with multiple adverse consequences in otherwise healthy asymptomatic individuals. We aimed to determine the prevalence of OH in an asymptomatic sample of veterans. Subject recruitment included 100 veterans, 96 males, with a mean age of 56 14 years, height of 174 9 cm and weight of 89 18 kg. Individuals were asked to lie on a clinic table for 10 min during which time BP was recorded every minute, subjects were then asked to move to the standing position and BP was recorded each minute for another 10 min. Mean SBP data did not differ between the supine and standing positions (132 15 vs. 132 18 mmHg); however, DBP was signicantly higher while standing (74 9 vs. 77 11 mmHg; p \ 0.001). Asymptomatic OH was evident in 27 individuals (27 %: OH+); within the rst 3 min of assuming the standing position SBP fell an average 32 mmHg (range -20 to -90 mmHg); DBP fell an average 16 mmHg (range -10 to -55 mmHg). Borderline OH (fall in BP of 1019/59 mmHg) was evident in an additional 26 subjects (26 %); 47 % of the subjects studied had no orthostatic fall in BP (OH-). The OH + group was statistically older than OH- group (61 12 vs.54 15 years, respectively; p \ 0.05); albeit not old, and was prescribed more anti-hypertension medications (2.6 2.1 vs. 1.5 1.6, respectively; p \ 0.05). These data suggest a relatively high prevalence of OH in otherwise healthy, asymptomatic, middleaged veterans, which may be attributable to the aggressive treatment of hypertension by clinicians in the Veterans Affairs healthcare system.

Abnormal autonomic ndings in chronic subjective dizziness: sympathetic dysfunction or hyperactivity

H. Lee, H.A. Kim Department of Neurology, Keimyung University School of Medicine, Daegu, South Korea Introduction: Dysautonomia is considered as a trigger factor of chronic dizziness, but there have been few reports about autonomic ndings in patients with chronic dizziness. Objectives: To investigate the frequency and the specic pattern of abnormal autonomic nding in chronic subjective dizziness (CSD) after strictly eliminating other trigger or cause of dizziness. Methods: From May to October 2011, we prospectively investigated the patients with CSD at the Dizziness Clinic of Keimyung University Dongsan Medical Center. For sorting patients with CSD without other causes or triggers, all patients took a routine medical check-up including history taking, physical examination, routine blood sampling, electrocardiography, chest X-ray and a detailed neurological examination, a quantitative audiovestibular testing, brain MRI or CT, and Symptom Checklist-90-Revised (SCL-90-R). Standardized autonomic function tests were performed including tilt table, Valsalva and heart rate deep breathing tests. The autonomic data were compared to these of 38 age-and sex-matched controls. Results: We identied 18 patients with CSD without other cause of dizziness. In 12 (67 %) patients, two patterns of autonomic abnormality were found: sympathetic dysfunction including orthostatic hypotension during tilt table test, reduction of phase II late or sympathetic index 3, or increase of phase II early or pressure recovery time during Valsalva test (n = 6); sympathetic hyperactivity including increased heart rate response during tilt table test or exaggerated phase IV during Valsalva test (n = 9). Discussion: Abnormal autonomic ndings may in part be associated with CSD. Sympathetic failure or hyperactivity may be postulated as a possible mechanism in chronic dizziness.

Poster #64 Combination ergotamine and caffeine for the treatment of orthostatic hypotension
C. Shibao, C.E. Ramirez, L.E. Okamoto, A.C. Arnold, A. Gamboa, P. Muppa, S.R. Raj, A. Diedrich, D. Robertson, I. Biaggioni Department of Medicine, Vanderbilt University, Nashville, TN, USA Orthostatic hypotension is the most disabling symptom of autonomic failure. Severely affected patients often require medication to counteract the blood pressure fall and to improve pre-syncopal symptoms on standing. Isolated clinical observations have suggested that the combination ergotamine and caffeine can be useful in the treatment of

Poster #66 Neurogenic mechanisms and venous physiology in patients with orthostatic intolerance
L. Saju1, Z. Sun2, R. Shields3, F. Fouad-Tarazi1 1 Department of Cardiovascular Medicine, Cleveland Clinic, Cleveland, OH, USA; 2Department of Quantitative Health Sciences, Cleveland Clinic, Cleveland, OH, USA; 3Department of Neurology, Cleveland Clinic, Cleveland, OH, USA

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256 Introduction: Accentuated venous pooling (Ac-VP) may be related to neuro-autonomic or circulatory disturbances and often plays an important role in orthostatic intolerance (OI). We assessed VP in patients with OI using a hemodynamic test (HEMO) and correlated the presence of accentuated VP (Ac-VP) with ndings on quantitated sudomotor axon reex test (QSART) to determine if abnormal QSART, as a measure of postganglionic sympathetic sudomotor function, predicted Ac-VP. Methods: The patient population (n = 181) included 55 males and 126 females (1887 years old) with a history of OI. HEMO is a nuclear test that measures an index of VP as the cardiopulmonary volume fraction to total blood volume. All patients had HEMO and QSART (01/2009 to 01/2010). Ac-VP and adequate VP (Ad-VP) were dened according to lab standards. Patients were divided between Ac-VP and Ad-VP and normal (NL) and abnormal (AB) QSART. Association between VP and QSART was assessed using X2 test. A logistic regression model was used to assess the relationship between HEMO response and QSART while controlling for age and gender. Results: 6 patients had Ad-VP + AB QSART, 74 patients had AcVP + AB QSART, 23 patients had Ad-VP + Nl QSART, and 78 patients had Ac-VP + Nl QSART. Ad-VP patients were more likely to have Nl QSART than Ac-VP patients (79.3 vs. 51.3 %, p = 0.005). Ac-VP patients were more likely to have AB QSART than Ad-VP patients (48.7 vs. 20.7 %, p = 0.005). After controlling for age and gender, Ac-VP patients were more likely to have AB QSART than Ad-VP patients (odds ratio: 3.401 [1.294, 8.943], p = 0.013). Conclusion: Ac-VP in OI patients is often associated with sympathetic hypofunction. Thus, assessing VP with QSART may help dene the pathophysiology of the VP and OI and provide information helpful in guiding therapeutic interventions.

Clin Auton Res (2012) 22:207258 Conclusions: These preliminary data indicate that differences in blood pressure and cerebral hemodynamics may inuence falling risk in these elderly individuals. This work has important implications for the use of noninvasive blood pressure and cerebral blood ow assessments as screening tools to assess risk for falls.

Poster #68 Arterial baroreex asymmetry: an additional mechanism of orthostatic insufciency in patients with non-cardiac syncope
O.V. Mamontov1, M.I. Bogachev2, E.V. Shlyakhto1 1 Almazov Federal Heart, Blood and Endocrinology Centre, SaintPetersburg, Russian Federation; 2Radio Systems Department SPb Electrotechnical University Orthostatic syncope genesis in patients without obvious heart disease is often unclear, even after becoming a specialized survey. We suggested that in some patients the syncope is associated with the asymmetry of arterial baroreex (ABR) indicated by the discrepancy between its activation (AF) and deactivation functions (DF). Aim: assessing neurogenic regulation of the circulation in patients with a positive tilt-test (TT), dependent their ABR activation and deactivation functions discrepancy. Patients and methods: The study included 74 patients without signicant cardiovascular disease, with syncope conrmed by TT (Italian protocol). Mean age was 41.5 18.8 years. During TT hemodynamics were recorded using blood pressure monitor (Finometer-PRO) and ECG. Also Valsalva maneuver and hand-grip test (HGT) were performed. ABR was evaluated using the rst differences time-domain method (AF and DF separately), and the asymmetry coefcient (AC) dened as [(DF - AF) 9 2/(DF + AF))] 9 100 % was calculated. Results: The average AC value was about 25 %. We found that patients with asymmetric reex (AR) (with AC was above 25 %, n = 36) were older than patients with AC below 25 % (n = 38): 52.7 16.9 % versus 30.8 13 %, p \ 0.001. They also had lower AF: 7.2 4.4 versus 13.6 7.6 ms/mm Hg, p \ 0.001, whereas the DF didnt differ: 12.1 6.8 and 13.5 8.4 ms/mm Hg, p [ 0.05. Heart rate reduction (vagal activation indicator) in presyncope was lower in AR group: 17.1 23.8 versus -39.7 25.7 beats/min, p \ 0.001. AC also varied in different types of syncope: cardioinhibitory 16 15 %, mixed 13 5 %, vasodepressor 32 8 %, and progressive orthostatic hypotension 47 8 %, F = 4.4, p \ 0.01. Diastolic blood pressure response to HGT was lower in AR group: 13.4 4.8 vs 18.3 8.4 mm Hg, p \ 0.001, while Valsalva index in these groups remained unchanged: 2.1 1.0 and 2.4 1.3, p [ 0.05. Conclusion: In patients with noncardiac syncope ABR asymmetry (due to reduced ABR activation) is common and associated with the age and predisposition to orthostatic insufciency. We attribute this asymmetry to the central modulation of ABR, since Valsalva index (which indicates the function of cardiac efferent) was similar in both groups, while blood pressure to HGT response (which indicates increased central sympathetic vascular tone) was reduced.

Poster #67 Mechanisms underlying the relationships between cardiovascular dysfunction and fall susceptibility in older adults
B.H. Shaw, S.N. Robinovitch, V.E. Claydon Department of Biomedical Physiology and Kinesiology, Simon Fraser University, BC, Canada Objectives: Cardiovascular impairments are a risk factor for falls. However, we need an improved understanding of the precise relationships between cardiovascular disease and fall susceptibility. The primary aim of this study is to evaluate the role of impairments in blood pressure and cerebral hemodynamics in falling risk in a cohort (n = 59) of long-term care residents. Method: We used portable equipment installed in two long-term care facilities to assess residents beat-to-beat blood pressure control in response to orthostatic stress while simultaneously monitoring cerebral blood ow. Medical records were used to assess covariates such as cognitive function, medication use, and mobility. These data will be compared to their 1 year retrospective and prospective falling risk as recorded through incident report forms. Results: Evaluation of falls within the previous year indicates that 53 % of subjects are previous fallers (1 or more falls in the previous year). Preliminary data from the cardiovascular risk assessment of 20 subjects indicates that previous fallers have lower resting cerebral blood ow (difference of 15.9 7.6 cm/s), and greater systolic blood pressure drops in response to orthostatic stress (difference of 11.5 9.7 mmHg) in comparison to non-fallers.

Poster #69 Myoclonic jerks in syncope are probably generated in the cortex
J.G. van Dijk1, R.D. Thijs1, J. van Niekerk1, W. Wieling2, D.G. Benditt3

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Clin Auton Res (2012) 22:207258 Department of Neurology, Leiden University Medical Centre, The Netherlands; 2Department of Internal Medicine, Academic Medical Centre, University of Amsterdam, The Netherlands; 3Cardiac Arrhythmia Center, Cardiovascular Division, University of Minnesota Medical School, Minneapolis, MN, USA Diagnosing syncope rests on identifying signs and symptoms. As severity of cerebral hypoperfusion is reected in either a slow (S) or a slow-at-slow (SFS) pattern, we studied signs of tilt-induced syncope at a 1 s resolution, using videos, EEG, blood pressure (BP) and heart rate (HR) to search for signs identifying S and SFS forms. Data were selected from consecutive tilt table tests. Inclusion relied on unconsciousness on video, BP and HR patterns and S or SFS EEG patterns. Among clinical events were oral, facial, arm and eye movements, eye closure, pupils, and sounds. EEG changes lasted longer in the SFS group (n = 38, 26 9 s.) than in the S group (n = 31, 17 6 s., p \ 0.001). Flattening lasted 12 8 s. Duration of the rst slow phase was inversely correlated to the at phase (p \ 0.001). The most common events were: eyes open, 93 %; dilated pupils, 77 %; sounds, 61 %; myoclonic jerks, 60 %. The following events occurred at signicantly different rates in the SFS vs. S groups: eyes open 100 vs. 83 %; sounds 82 vs. 38 %; eyes upwards: 83 vs. 23 %; roving eye movements: 43 vs. 0 %. Myoclonic jerks occurred almost exclusively during S phases (p \ 0.001); in fact, ongoing jerks were abolished by attening. These ndings help differentiate more and less severe cerebral hypoperfusion in syncope. The absence of myoclonic jerks during EEG attening argues against the common belief that they are due to cortical disinhibition; a cortical origin is likely.
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257 06001800 h); (T2 = 18002400 h); (T3 = 24000600 h). Glucose averages for the 72 h time period were also calculated. Results: Despite similar Hgba1c, OSA patients with QTc \ 440 mm had more HYPO than those with QTc C 440 mm for all time periods (T1 = 6 2 vs. 2 1 %; p \ 0.06), (T2 = 73 vs. 2 1 %; p \ 0.05), and (T3 = 72 vs. 1 1 %; p \ 0.05), as well as overall 72 h (6 2 vs. 2 1 %; p \ 0.05). Patients without OSA had no signicant differences for HYPO. DM with OSA had a higher BMI than those without OSA (p \ 0.01). Conclusions: Glucoregulation in OSA may depend upon the integrity of the autonomic nervous system, since patients with QTC \ 440 mm were more likely to be vulnerable to hypoglycemia. Therefore, it is important to evaluate autonomic function when recommending a regimen of tight glycemic control in older male DM with OSA. Acknowledgements: Research sponsored by JAL FHCC

Poster #71 A case of paraneoplastic autonomic failure preceding Hodgkins lymphoma

P. Muppa, C.E. Ramirez, B. Black, D. Robertson, A. Peltier, S.R. Raj, C. Shibao, I. Biaggioni Autonomic Dysfunction Center, Division of Clinical Pharmacology, Department of Medicine, Vanderbilt University School of Medicine, Nashville, TN, USA We report a rare case of Hodgkins Lymphoma (HL) with initial presentation of autonomic failure and generalized lymphadenopathy. A 27-year-old previously healthy male was referred to our clinic with recurrent syncopal episodes, panic attacks, and constipation. Clinical examination revealed profound orthostatic hypotension (121/83 mm of Hg supine and 81/65 mm of Hg after 1 min of standing) with preserved heart rate response on standing (heart rate increase from 78 to 103 beats per minute). Autonomic function test showed a blunted sinus arrhythmia ratio of 1.07 (normal [1.2). The patients Valsalva maneuver showed blunted pressor response on phase II late and phase IV, which is consistent with sympathetic vasoconstrictor failure and abnormal cardiovagal response. He also had left supraclavicular lymphadenopathy. Considering initial presentation of pandysautonomia, the patient underwent screening for autoimmune autonomic failure. His paraneoplastic panel including antibodies against autonomic ganglia (Anti-AChR) was negative. He was diagnosed with sub-acute autonomic failure of unidentied etiology and prescribed with midodrine. Initial biopsy of lymph nodes from mediastinum showed reactive hyperplasia, but not lymphoma. The patient received empirical treatment with plasma exchange, which gave him a temporary symptom relief for 2 days. His symptoms (syncopal episodes while sitting, increase in number of panic attacks, constipation) worsened over the course of next few months, conning him to a wheel chair. Repeat biopsy of lymph nodes from mediastinum showed classical HL. A paraneoplastic antibody panel still failed to detect any known autoantibodies. The patient, however, showed signicant clinical improvement after the rst cycle of chemotherapy. Autonomic function test performed 1 year after the therapy showed normal cardiovagal response, however his sympathetic vasoconstrictor response was still abnormal. We conclude that this is a rare case of paraneoplastic autonomic failure associated with Hodgkins Lymphoma. Treatment of underlying malignancy with chemotherapy reversed cardiovagal dysfunction but not sympathetic failure.

Poster #70 Glucoregulation and autonomic function in older male patients with diabetes mellitus and obstructive sleep apnea
J.L. Gilden, J. Cheng, B. Theckedath, P. Hung, J. Stoll Department of Medicine/Diabetes & Endocrinology, Rosalind Franklin University of Medicine and Science/Chicago Medical School, and JAL Federal Health Care Center, North Chicago, IL, USA Objectives: Although glycemic control is important for prevention of complications in Diabetes Mellitus (DM), ACCORD and ADVANCE studies suggest that mortality is higher in patients with extremely tight glucose control, especially in those with longer DM duration and already established chronic complications. The increased hypoglycemia (HYPO) may be responsible for further autonomic failure (AN), and sudden death. In addition, Obstructive Sleep Apnea (OSA), a common condition in DM, and in patients with autonomic neuropathy, is also associated with increased risk of sudden death. Therefore, we evaluated whether glucoregulation is altered by AN in older male DM with symptomatic OSA. Methods: A retrospective chart review of 77 DM [(21 Type 1: 56 Type 2) (age = 63 1.3 years) (BMI = 33.3 0.85) (Duration DM = 18.0 11.3 years) (HbA1c = 7.95 1.7 %) (BezettQTc = 439 5.0 mm)] identied 29 patients with signicant OSA, conrmed by polysomnography (AHI = 33.57 6.7), who had unbiased glucose measurements by 72 h continuous glucose monitoring system (CGMS). Glucose values were then mathematically transformed into % time above normal ([140 mg %), % normal (70140 mg %), and % below normal (\70 mg %) for 3 time intervals: (T1 =

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Clin Auton Res (2012) 22:207258 severe sudomotor failure. Cardiovascular adrenergic function showed only modest impairment, cardiovagal function had returned to normal. Plasma NE was 94 supine and 149 pg/ml upright. Conclusions: 11-year follow-up in a young patient with seronegative AAG revealed denite but incomplete improvement of autonomic function and symptoms. Sudomotor and erectile function remained markedly impaired. This report parallels prior short-term follow-up reports of an overall favorable prognosis but often incomplete recovery from both seronegative and seropositive AAG. The long duration of selected decits would suggest structural impairment beyond functional blockade of ganglionic function. Supported by NIH (NS32352, U54NS065736, K23NS075141, UL1RR24150), and Mayo Funds.

Poster #72 11-year follow-up of a case of autoimmune autonomic ganglionopathy

W. Singer, D.M. Sletten, T.L. Gehrking, A.K. Parsaik, P.A. Low Department of Neurology, Mayo Clinic, Rochester, MN, USA Objective: To describe the natural disease course of a patient with seronegative autoimmune autonomic ganglionopathy (AAG) over a timeframe of 11 years with standardized assessment of autonomic symptoms and function. Background: AAG is an immune-mediated autonomic disorder usually presenting as acute pandysautonomia. The pathophysiology of this disorder has been well characterized owing to the discovery of nicotinic ganglionic acetylcholine receptor antibodies in patients with AAG. Nevertheless, the majority of cases presents without detectable autoantibodies. Little is known about the long-term course and prognosis of AAG in general and seronegative AAG in particular. Methods: We followed a case of seronegative AAG for 11 years, with serial evaluations from 1 month to 11 years after disease onset. In addition to routine clinical and laboratory assessments, standardized autonomic testing (autonomic reex screen, ARS; thermoregulatory sweat test, TST; plasma catecholamines) and standardized assessment of autonomic symptoms and function (composite autonomic symptom score, COMPASS) were completed. Results: The patient presented at age 17, 1 month after subacute onset of abdominal pain, vomiting, bloating, constipation, orthostatic hypotension, anhidrosis, urinary retention, and erectile dysfunction. ARS showed generalized autonomic failure with widespread sudomotor impairment, severe cardiovascular adrenergic, and moderate to severe cardiovagal failure (CASS score = 9 out of 10). Treatment with IVIG resulted in negligible benet and was discontinued. Upon re-evaluation 1 year later, most symptoms had modestly improved. COMPASS score was 61.3 out of 200. CASS score was 7 related to improvement in cardiovagal function. TST showed global anhidrosis except for small islands of preserved sweating. Plasma norepinephrine (NE) was 199 pg/ml and failed to increment in the upright position. By 11 years after symptom onset, symptoms had improved markedly and he had returned to a near normal level of functioning without further immunomodulatory therapy. Remaining symptoms included severe erectile dysfunction and lack of thermoregulatory abilities. COMPASS was improved to 34. There was unchanged

Poster #73 Autonomic function test outcomes in diabetes mellitus

L.B. Tay, S. Srinivasan, C. Kang, T. Umapathi Department of Neurology, National Neuroscience Institute, TTSH Campus, Singapore We evaluate the autonomic function test outcomes of 123 diabetic patients referred over a 5 year period from 2007 to 2011. There were 93 patients with abnormal autonomic function testing (75.6 %). In comparison with the control group (n = 30), there was a signicant difference in resting heart rates (75 13 vs. 70 12, p = 0.05). In addition, there was a signicant difference in the degree of drop of systolic blood pressures with postural change (36 24 vs. 16 19 mmHg, p \ 0.01), diastolic drop in blood pressure with postural change (14 12 vs. 3 10 mmHg, p \ 0.01) and diastolic blood pressure changes with isometric exercise (7.5 7 vs. 15 7 mmHg, p \ 0.01). The most sensitive tests were postural drop in diastolic blood pressure (95.7 %, PPV 80.2 %) and postural drop in systolic blood pressure (92.5 %, PPV 78.2 %). Diastolic blood pressure change to isometric exercise was specic (83.3 %) but not sensitive (58.1 %) in picking up autonomic dysfunction. None of the tests had high negative predictive values. In summary, we found that resting heart rates, postural blood pressure changes and diastolic blood pressure changes to isometric exercise are useful in assessing diabetic autonomic neuropathy.

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