Resuscitation 56 (2003) 215
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www.elsevier.com/locate/resuscitation

Survival and normal neurological outcome after CPR with periodic

Gz acceleration and vasopressin
Jose A. Adams *, Jorge Bassuk, Dongmei Wu, Paul Kurlansky
Divisions of Neonatology, Department of Research, Mount Sinai Medical Center, and Miami Heart Research Institute, Miami Beach, FL 33140, USA

Received 31 May 2002; received in revised form 1 August 2002; accepted 18 August 2002

Abstract

Background: We showed previously that whole body periodic acceleration along the spinal axis (pGz) is a novel method of
cardiopulmonary resuscitation (CPR). The ultimate assessment of the value of any CPR technique is the neurological outcome after
using such a technique. In this study, we determined the neurological outcome in pigs after prolonged pGz
/CPR, with
administration of vasopressin immediately prior to defibrillation. Neurological outcome after pGz
/CPR was compared to a control
group where no intervention occurred for the same time period (C-NoInterv). Methods and Results: Ventricular Fibrillation (VFIB)
was induced in 12 animals. After a 3 min non-interventional interval, the animals received either pGz
/CPR (n /7), or C-NoInterv
(n /5) for 15 min. After 18 min of VFIB, a single dose of vasopressin (0.8 U/kg) was administered along with sodium bicarbonate
and bretylium, and defibrillation was attempted. All animals in the pGz
/CPR group had return of spontaneous circulation (ROSC)
and normal neurological assessment at 24 h. Neurologic outcome remained normal at 48 h. In contrast, none of the animals in the
C-NoInterv had ROSC. Conclusion: Prolonged pGz
/CPR, with administration of vasopressin immediately prior to defibrillation
results in normal neurological outcomes at 24 h.
# 2002 Elsevier Science Ireland Ltd. All rights reserved.

Keywords: Cardiopulmonary resuscitation; Periodic acceleration; Neurological outcome; Vasopressin; Pigs

Resumo

Contexto: Nós já tinhamos demonstrado que a aceleração periódica de todo o corpo ao longo do eixo espinal (pGz) é um novo
método de reanimação cardio-pulmonar (RCP). O melhor dos critérios para avaliação da eficácia das técnicas de RCP é a avaliação
do prognóstico neurológico associado à utilização dessa técnica. Neste estudo avaliamos o prognóstico neurológico em porcos após
PCR-pGz isolado prolongado, com administração de vasopressina imediatamente antes da desfibrilhação. O prognóstico
neurológico após PCR-pGz foi comparado com um grupo controlo onde não ocorreu nenhuma intervenção durante o mesmo
perı́odo de tempo (C-NoInterv). Método e resultados: Foi induzida Fibrilhação Ventricular (VFIB) em 12 animais. Após um
perı́odo de 3 minutos sem intervenção, os animais formasubmetidos A PCR-pGz (n /7), ou C-NoInterv. (n /5) durante 15 min.
Após 18 min. de VFIB, foi administrada uma dose única de vasopressina (0.8 U/Kg) juntamente com bicarbonato de sódio e bretı́lio
e foi tentada a desfibrilhação. Todos os animais do grupo PCR-pGz tiveram recuperação da circulação espontânea (ROSC) e
avaliação neurológica normal às 24 h. O prognóstico neurológico permaneceu normal às 48 h. Em contraste, nenhum dos animais
no C-NoInterv. Recuperou circulação espontânea. Conclusão: A PCR-pGz prolongada, com a administração de vasopressina
imediatamente antes da desfibrilhação resultou numa avaliação neurológica normal às 24 horas.
# 2002 Elsevier Science Ireland Ltd. All rights reserved.

Palavras chave: Reanimação Cardio-Pulmonar; Aceleração periódica; Prognóstico Neurológico; Vasopressina; Porcos

* Corresponding author. Address: Divisions of Neonatology, Mount Sinai Medical Center, 4300 Alton Road, 3 Blum, Miami Beach, FL 33140,
USA. Tel.: /1-305-674-2727; fax: /1-305-674-2306.
E-mail address: tony@msmc.com (J.A. Adams).

0300-9572/02/$ - see front matter # 2002 Elsevier Science Ireland Ltd. All rights reserved.
PII: S 0 3 0 0 - 9 5 7 2 ( 0 2 ) 0 0 3 1 9 - 2
216 J.A. Adams et al. / Resuscitation 56 (2003) 215
/221

Resumen

Antecedentes : Mostramos previamente que la aceleración periódica de todo el cuerpo a lo largo del eje espinal (pGz) es un método
novedoso de reanimación cardiopulmonar (RCP). El resultado neurológico es última evaluación de utilidad de una técnica de RCP,
una vez impartida esta. En este estudio, determinamos el resultado neurológico en cerdos después de RCP con pGz prolongada
solamente, con administración de vasopresina inmediatamente antes de desfibrilar. El resultado neurológico después de RCP con
pGz fue comparado con un grupo control donde no se realizó ninguna intervención en el mismo perı́odo de tiempo (C-NoInterv).
Métodos y Resultados : Se indujo fibrilación ventricular (VFIB) en 12 animales. Después de un intervalo de 3 minutos sin
intervención, los animales recibieron ya fuera RCP con pGz (n /7), o no intervención (C-NoInterv) por 15 minutos (n /5).
Después de 18 minutos de VFIB, se administró una dosis única de vasopresina (0.8 U/kg) junto con bicarbonato de sodio y bretillo,
y, se intentó desfibrilación. Todos los animales con RCP con pGz alcanzaron retorno a circulación espontánea (ROSC) y evaluación
neurológica normal a las 24 horas. La evaluación neurológica se mantuvo normal a las 48 horas. En contraste, ninguno de los
animales en el grupo C-NoInterv tuvo ROSC. Conclusión : RCP con pGz prolongada, con administración de vasopresina
inmediatamente antes de desfibrilar lleva a resultado neurológico normal en 24 horas.
# 2002 Elsevier Science Ireland Ltd. All rights reserved.

Palabras clave: Reanimación cardiopulmonar; Aceleración periódica; Resultado neurológico; Vasopresina; Cerdos

1. Introduction a control group that underwent the same protocol

We showed previously that whole body periodic
acceleration along the spinal axis (pGz) is a novel
method of cardiopulmonary resuscitation (CPR) [1].
Biomechanical forces induced by pGz produce ventila-
tion and increase capillary blood flow secondary to
vasodilatation. The produced biomechanical forces
during pGz not only stimulates vasodilatation by
mediator release at the vessel wall but also establishes
small pressure gradients across the heart which are
sufficient to drive blood through the cardiovascular
system during the period of decreased peripheral vas-
cular resistance resulting from pGz-induced vasodilata-
tion [1,2]. In a porcine model of ventricular fibrillation
(VFIB) following prolonged CPR, we demonstrated
that return of spontaneous circulation (ROSC) occurs
after application of pGz
/CPR at a frequency of 2 Hz
and Gz of 9/0.6 [1]. During the ROSC period, arterial
blood pressure and arterial blood gases remained
normal without additional circulatory support.
The ultimate assessment of the value of any CPR
technique is the neurological outcome after using such a
technique. Wenzel et al. reported full neurological
recovery in pigs that received vasopressin during con-
ventional manual CPR compared to a group that
received epinephrine (adrenaline) or placebo [3]. In our
earlier pGz resuscitation study of 2 h follow-up after
ROSC, there was no need for antiarrhythmic drugs or
excessive correction of acidosis. On the basis of vaso-
pressin successes in recovery [4
/8], we reasoned that
pGz combined with vasopressin might produce a
prolonged favorable neurological outcome. The purpose
of this investigation was to determine the neurological
outcome after prolonged pGz
/CPR, with administra-
tion of vasopressin immediately prior to defibrillation.
Neurological outcome after pGz
/CPR was compared to
except that during the 18 min of VFIB there was no
intervention. (C-NoInterv).
2. Method
This study complies with the Ustein-Style Guidelines
for Uniform Reporting of Laboratory CPR Research
[9].
2.1. Platform design
The motion platform that imparts whole body
periodic acceleration has been previously described
[1,2,10,11]. Briefly a horizontal wooden platform is
driven with a linear displacement motor powered by
an amplifier that is controlled by a sine wave controller
(Non Invasive Monitoring Systems, Inc. North Bay
Village, FL). The latter allows control of frequency and
displacement of the platform. The platform is directly
driven by the underlying motor and articulates across
the frame on stainless steel tracks and nylon wheels. The
unit has a maximum weight capacity for animals of
about 30 kg and operates at a frequency between 0.5
/10
Hz at a force of 0.1
/1.5 /G [11] (Fig. 1).
2.2. Animal preparation
All animal studies were approved by the Institutional
Animal Care and Use Committee and were in compli-
ance with the Animal Welfare Act. Twelve juvenile pigs
(109/2.5 kg) were used in this study. The animals were
initially anesthetized with ketamine (10 mg/kg, i.m.) and
maintained in a surgical plane of anesthesia with
intravenous propofol. Intubation of the trachea and
placement of intravascular catheters was performed
 J.A. Adams et al. / Resuscitation 56 (2003) 215
/221
Fig. 1. Schematic diagram of the pGz platform, along with direction of motion of the ribcage (Rc) and abdomen (Ab) during one cycle.
under sterile conditions. An airway was established
using a 5.0 mm tracheal tube. Intravascular catheters
were placed into the femoral artery to measure systemic
blood pressure by connecting the fluid filled catheter to
a pressure transducer (Transpac† , Abbott Critical Care
Systems, North Chicago, IL). A right atrial catheter was
placed via the left external jugular vein for administra-
tion of fluids and drugs. Arterial blood gases were
measured at various intervals during the experiments
using a blood gas analyzer (Radiometer model ABL 30).
A bipolar fibrillating wire was placed subcutaneously
across the apex of the heart for the delivery of 30 V of
AC current at 60 Hz to induce VFIB, a standard ECG 3-
lead harness was placed on the chest to monitor ECG,
and a pair of defibrillating electrodes (Fast Patch† Plus,
Physio-Control, Corp., Redmond, WA) was placed
across the chest for defibrillation by connecting the
electrodes to a LifePak 8 defibrillator (Physio-Control
Corp., Redmond, WA). Periodic acceleration (pGz) was
achieved by supporting the animal on the oscillating
motion platform in the supine position. The platform
moved sinusoidally in a headword-to-footward direc-
tion, which allowed for the control of both the
frequency and the force of acceleration. During pGz,
platform acceleration was measured using an acceler-
ometer (NIMS, Inc. model 140
/060, Miami Beach, FL).
All animals were paralyzed with pancuronium bromide
(0.1 mg/kg) and received a bias flow of 100% O2, with
CPAP of 5 cm H2O to maintain oxygenation and
functional residual capacity, respectively.
2.3. Experimental design
The experimental design and time line in this series is
depicted in Fig. 2. Twelve animals were studied in total.
217
None of the animals received heparin prior to resuscita-
tion attempt in accordance with our previous protocol
[1]. All animals received intravenous saline during the
fibrillation period at a rate of 7 ml/min, and no
medications were used during this period for any of
the groups. In seven consecutive animals the motion
platform was activated (pGz
/CPR). Five animals
served as a control where no intervention was performed
throughout the entire VFIB time period (C-NoInterv).
VFIB was induced and after a 3 min interval of non-
intervention (during the 3 min non-intervention period,
none of the animals received ventilatory support), they
received either pGz
/CPR or continued without inter-
vention (C-NoInterv) for 15 min. pGz was applied as
previously described at a frequency of 2 Hz and 9/0.6
Gz with a bias flow of 100% oxygen and CPAP of 5 cm
H2O [1]. The motion of the platform produces ventila-
tion by setting the diaphragm in motion with each
acceleration and deceleration without need for conven-
tional positive pressure ventilation [1,2,10,11]. Animals
in the C-NoInterv only group received a bias flow of
100% oxygen and a CPAP of 5 cm H2O but no
conventional positive pressure ventilatory support.
After 18 min of VFIB, the animals underwent a 2
/3
min period of conventional manual chest compressions
( /1/s) to decompress the engorged ventricles in the pGz
group and C-NoInterv, as in our previously published
protocol [1]. During the decompression phase of the
protocol, the following drugs were administered i.v.;
bretylium 5 mg/kg, vasopressin 0.8 U/kg (Sigma, St
Louis, MO), and sodium bicarbonate 10 mEq. Defi-
brillation was then initiated by a series of DC shocks (15
J/kg) delivered to the remotely placed defibrillating pads
by the defibrillator (LifePak 8). Up to five shocks were
given to attempt to restore ROSC in each group of
218 J.A. Adams et al. / Resuscitation 56 (2003) 215
/221
Fig. 2. Diagram of the experimental protocol
animals. Inability to achieve ROSC after five defibrillat-
ing shocks resulted in termination of the experiment.
Animals that achieved ROSC were given sodium
bicarbonate after 5 min to correct the arterial blood
gas values obtained after 5 min of spontaneous circula-
tion. No further pharmacological intervention was given
after this point.
The surviving animals were weaned off all support by
4 h. They received maintenance fluids of dextrose 5%
with normal saline at a rate of 50 cm3/h and a single
dose of ampicillin (200 mg/kg), Cefotaxime (50 mg/kg)
and butorphenol (0.1 mg/kg). At the end of 4 h after
return of spontaneous activity and normal respiratory
efforts the animals were decanulated, extubated and
transported to their pen.
2.4. Neurological and functional assessment
All surviving animals were assessed at 24 and 48 h
after CPR. They were evaluated using two scales
previously documented for their use in pig survival
studies as follows. The Neurologic Deficit Score for Pigs
assigns values for deficits in neurological function, a
score of 0 is normal and a score of 400 is brain death
[3,12,13]. The cerebral performance category (CPC) is a
more overall assessment of neurological function, with a
category of 1 being normal and 5 brain death. A video
camera was also used to document the status of the
animal at 24 and 48 h.
2.5. Data analysis
Data were analyzed for frequency distribution analy-
sis and were found to have followed a Gaussian
distribution. The data were analyzed using analysis of
variance with Bonferroni’s post-test for repeated mea-
sures. Survival data were analyzed by non parametric
analysis Mann-U-Whitney. Differences in sample means
were considered statistically significant if P B/0.05.
Values in the text and tables are reported as mean
(S.D.).
3. Results
All animals (100%) in the pGz
/CPR group survived,
whereas none of the animals in the C-NoInterv had
ROSC. Blood gases for the two groups of animals are
listed in Table 1. There were significant decreases in
PaO2 in all animals compared to baseline levels. During
VFIB the pGz
/CPR group had significantly higher
PaO2 215(20), 152(18) torr compared to C-NoInterv
174(18), 98(17) torr at 5 and 15 min of VFIB,
respectively, (P B/0.05).
Fig. 3 summarizes the mean blood pressure values for
both groups. After VFIB, pGz
/CPR maintained mean
blood pressures of 26(3.3) 19.9(4.8) and 20.5(4.3) mmHg
compared to C-NoInterv of 14(0.5) 11(1.3) and 10(1.4)
mmHg at 5,10, and 15 min of VFIB, respectively, (P B/
0.05). Mean right atrial pressure during pGz
/CPR was
15(3), 11(2), and 10(1) mmHg compared to C-NoInterv
of 5(1),7(1), and 7(1) mmHg at 5,10, and 15 min of
VFIB, respectively, (P B/0.05). The data from Fig. 2
also imply that the driving pressure for blood flow
during pGz
/CPR in these animals was about 8
/11
mmHg during pGz
/CPR. Upon return to a sponta-
neous circulation in the pGz
/CPR group, there were no
differences at 30, 60, 120, 180 and 240 min in mean BP
compared to the baseline values. The average time for
ROSC in animals undergoing pGz
/CPR was 2 min.
After ROSC, animals received sodium bicarbonate to
correct metabolic acidosis. The average amount of
sodium bicarbonate was 10 meq after ROSC. Extuba-
tion of the surviving animals was accomplished at a
 J.A. Adams et al. / Resuscitation 56 (2003) 215
/221 219

Table 1
Arterial blood gases during the CPR protocol

pH PCO2 (Torr) PaO2 (Torr) HCO3 (meq/dl)

pGz
/CPR C-NoInterv Pgz
/CPR C-NoInterv pGz
/CPR C-NoInterv pGz
/CPR

BL 7.37(0.027) 7.35(0.030) 41.5(1.5) 34.5(2.0) 493(35) 424(28) 23.8(2.4) 22(2.5)

VFIB 5 7.36(0.047) 7.34(0.02) 41(2.0) 34(2.6) 215(20) 174(18) 20.5(3.0) 18.5(2.6)
VFIB 15 7.32(0.026)a 7.10(0.024) 41(2.6)a 54(1.5) 152(18)a 98(17) 20.8(2.7)a 16(1.8)
ROSC 30 7.26(0.02) 35.1(2.2) 125(15) 15.3(3.0)
ROSC 60 7.30(0.03) 33.2(3.0) 142(20) 15.8(2.2)
ROSC 120 7.38(0.035) 34.5(2.9) 131(12) 20.3(2.2)
ROSC 180 7.36(0.02) 38.4(3.5) 147(11) 21(2.8)

Values are mean9/S.E.M.

a
pGz
/CPR vs C-NoInterv (P B/0.05).

median of 3 h. All surviving animals were upright, and

drinking from the trough by 10 h after ROSC. Neuro-
logical assessment was performed independently by JA,
JB, DW at 24 and 48 h. All animals had a score of 0
(Normal) on the neurological deficit score (NDS) and a
score of 1 (Normal) on the CPC. All investigators
agreed on the NDS and CPC scores.

4. Discussion

The results of this study indicate that a normal

Fig. 3. Mean arterial blood pressure and mean right atrial pressure;
Baseline Values (BL), VFIB values at 5, 10, and 15 min, and, during
ROSC at 30, 60, 120, 180 and 240 min during the CPR protocol. a/
pGz
/CPR vs C-NoInterv; b /pGz
/CPR and C-NoInterv BL vs
VFIB (P B/0.05) Values are mean9/S.E.M.
neurological outcome can be achieved in animals with
induced prolonged VFIB using pGz
/CPR. The protocol
of 3 min of non-intervention time followed by 15 min of
intervention using pGz
/CPR represents a prolonged,
and rigorous method of testing this CPR technique. Our
control group was specifically designed to test the effect
of non-intervention, which did not produce ROSC.
Since the ultimate assessment of any CPR technique
relates not only to the hemodynamic changes it provides
but the neurological survival status, our results suggest
that pGz
/CPR may be a highly effective method for
achieving normal survival.
Our study was designed as an extension to our
previously published work [1] and to evaluate the effects
of pGz
/CPR on myocardial and neurological functions
without introducing a large number of confounding
factors. Thus, the fact that pGz
/CPR produced ROSC
without cardiac arrhythmias requiring additional med-
ications during survival implies that this method permits
adequate myocardial preservation during CPR Normal
neurological function after ROSC suggests that cerebral
oxygenation and perfusion were adequately maintained
during pGz
/CPR. We previously discussed the plausi-
ble mechanisms of blood flow during pGz
/CPR [1].
Briefly, vasodilatation and low vascular resistances
produced by pGz, allow blood flow under the low
perfusion pressure gradients that are generated by the
motion platform (pGz). This finding is confirmed by the
present study.
220 J.A. Adams et al. / Resuscitation 56 (2003) 215
/221
The major differences between the current protocol
and other published protocols for resuscitation relate to
(a) the total amount of time in VFIB (b) the absence of
medications during the 18 min of VFIB (c) administra-
tion of single doses of vasopressin (0.8 U/kg), bretylium
and sodium bicarbonate prior to defibrillation (d) lack
of intensive care in the post-defibrillation state and (e)
no continued administration of antiarrhythmic drugs,
pressor support or volume expansion after ROSC.
These differences are vital in comparing other studies
to ours. We analyzed all studies in which swine were
used as experimental animals for resuscitation where the
total VFIB time was at least 15 min and neurological
outcome was evaluated for at least 24 h. Wenzel et al.
studied pigs in the 30
/40 kg weight category in an
experimental protocol of VFIB, with 4 min of bystander
non-intervention followed by manual conventional
CPR. They used multiple doses of vasopressin, and
compared this intervention to epinephrine and a saline
group [3]. They found that the vasopressin group had
100% ROSC whereas none of the epinephrine or saline
group had ROSC. Neurological evaluation at 24 h
showed unsteady gait, but at 96 h all animals had a
NDS of 0/400 (Normal). In contrast, all our animals had
steady gait at 24 h and neurological function remained
normal at 48 h. The total time reported by Wenzel et al.
for initiating defibrillation was 22 min, the same as used
in our study. However, there are important differences
between Wenzel’s study and the current investigation.
We administered a single dose of vasopressin 0.8 U/kg at
the end of the 18 min of VFIB whereas Wenzel et al.
gave three doses of vasopressin of 0.4 U/kg, 0.4 U/kg
and 0.8 U/kg at 3, 8, and 13 min, respectively, of manual
CPR. The total cumulative dose in Wenzel’s study was
1.6 U/kg. In our study the total dose of vasopressin was
only 0.8 U/kg (50% less than Wenzel’s study). In
addition, they gave lidocaine, amiodorone, dopamine,
phenylephrine and nitroglycerin as required after
ROSC. In contrast to their study, after ROSC we did
not administer additional pressor or antiarrhythmic
cardiac medications.
Hilwig et al. studied swine weighing approximately 28
kg using a VFIB protocol with a bystander untreated
time of 1 min and 15 min of Basic Cardiac Life Support
and Advance Cardiac Life Support, and tested four
intravenous catecholamine regimes. The standard dose
epinephrine group had the best outcome with 10/12
(83%) ROSC and normal neurological survival in 9/12
(75%) [14]. This outcome contrasts with our study of
prolonged VFIB of 229/1 min with 100% normal
neurological survival. Babar et al. compared a single
dose of vasopressin and three doses of epinephrine in a
protocol that used 2 min of non-intervention bystander
time and total of 18 min of VFIB. These investigators
found ROSC to occur in 12/18 (67%) with normal
neurological function of 61% at 24 h Intensive care was
provided to those animals that had ROSC [15].
Paiva et al. used mechanical devices such as minimally
invasive cardiac massage, in a protocol of VFIB with 3
min non-intervention bystander time and 16 min of
VFIB. These investigators reported survival at 24 h of 1/
10 with a severely disabled neurological outcome [16].
The non-intervention period of 3 min used in our
study was derived from the median of published survival
and non survival resuscitation studies and our pre-
viously published work [1]. Wenzel et al.’s non-inter-
ventional time was 4 min, Hilwig’s 1 min and Babar’s 2
min [3,14,15]. Therefore, this difference in non-interven-
tion times could not account for the differences we
obtained in neurological outcome. The preceding studies
used larger adult pigs in the range of 25
/40 Kg [3,14
/
16] and our younger, smaller weight animals might have
had a different response.
In conclusion, we demonstrated that neurological
outcome using pGz
/CPR is at least equivalent to the
best outcomes published to date [3]. This is the first
report in the medical literature of a CPR technique that
did not require vasoactive substances during the period
of CPR and yet achieved normal neurological function
upon recovery. The simplicity of pGz
/CPR in combi-
nation with only a single dose of vasopressin at the point
of defibrillation needs to be tested in larger animals
before embarking on human clinical trials. In addition,
optimization of the intensity and rate of pGz, and use in
larger adult animals needs investigating. pGz
/CPR has
a promise of supporting the circulation of individuals at
high risk of cardiac arrest or VFIB.
Acknowledgements
This work was supported by a grant from the Miami
Heart Research Institute. We gratefully acknowledge
the scientific input of Marvin A. Sackner, M.D. and
William Abraham, PhD., and the graphical assistance of
Michael Ingman.
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