Myogenic Theory Explains!

"The Thrombogenic Theory of Myocardial Infarction Tumbled Down and the Orthodoxy
Didn’t Have Noticed"
Quintiliano H. de Mesquita, M.D.
Originally published at Infarct Combat Project

The orthodox cardiology stay repressed in their therapeutic behavior in front of

coronary- myocardiopathy, since when the thrombogenic theory (TT) started to tumble
down after 25 years of clinical research (1944-69), with the recognition about the failure
of coumarin and heparin anticoagulants to stop the unstable angina (UA) and in
prevention of myocardial infarction (MI).
During 10 years (1944-54) we have participated in clinical studies about
anticoagulants, recording its failure to stop the UA and in the MI prevention, what led
us to reject such therapeutic agents.
In 1969, with the general admission of the anticoagulants failure, happened the
introduction of the coronary bypass surgery practiced directly in man, without the
previous assessment in experimentation animals.
Consequently, heart surgeons and cardiologists with no other visible way to manage
chronic coronary-myocardiopathy and acute coronary syndromes, have assumed
together the compulsive interventionism practiced during the last 3 decades:
myocardial reperfusion through angioplasty and/or coronary bypass surgery.
At the same time they indicate coronary dilators, antiaggregate of platelets and beta
blockers. Beta blockers, in our point of view, represent a contradictory behavior by the
cardiologists in front of the contractile deficient condition of the dependent coronary
myocardial segment, frequently developing generalized hypotonia.
The only actual concern by the orthodox cardiologist is to provide the myocardial
reperfusion in any case, independently of sex or age, without any future guarantee
regarding the success of the reperfusion act, generally submitted to the repetition
practice due to its frequent failure.
In 1972, we developed the myogenic theory (MT) stating the acute myocardial
infarction (AMI) as cause and not consequence of coronary thrombus. The myogenic
theory met important support in pathological anatomy findings since 1950 decade
whose authors preconized the coronary thrombus as consequence of acute myocardial
infarction.
According the myogenic theory concepts the AMI is developed by functional
degradation state of the regional coronary-dependent myocardium characterized by a
pathophysiology essentially myogenic, in the 3 stages of coronary-myocardiopathy:
I. The stable angina with or w/out previous myocardial infarction, developed by
exertion or emotion and producing regional ventricular ischemia (RVI),
coronary-dependent, in which the negative inotropic action develops the
regional myocardial insufficiency (RMI), reciprocal, ceasing with the stop of the
provoking cause.
II. The unstable angina (UA) as a spontaneous, reversible and recurrent
syndrome resulted from an abrupt and unexpected RMI followed by RVI of long
duration and resistant to all available therapeutic agents.
III. The UA is perpetuated in the last crises of angina with its transformation in
infarctioning clinical picture (ICP) represented by RMI + RVI -> myocardial
infarction -> myocardial necrosis -> coronary thrombosis not obligatory;
 electrocardiographically recognized as myocardial infarction with Q wave and
w/out Q wave.
In front of this pathophysiological mechanism the cardiotonic appeared as a new
therapeutic concept, and since 27 years ago proves to be capable to preserve the
myocardial and symptomatic stability in the stable angina pectoris with or w/out
previous infarction, to stop the UA and to provide the transformation of infarctioning
clinical picture in avoided myocardial infartion, ICP- interrupted myocardial infarction or
characterized as ICP-infarcted according the behavior of enzymatic peaks.
In 1981 the thrombogenic theory suffered the final tumble down when the
thrombolytics, which were reintroduced in the UA and AMI, showed that they are
ineffective regarding the clinical events in the UA and passed to be indicated only in the
treatment of AMI.
During the last 2 decades has been clearly demonstrated in vast literature that,
thrombolytics and angioplasty release the coronary arteries related with the MI, while is
recorded the coronary/dependent ventricular dysfunction process.
Gregorini, L et al, in a recent article (Circulation, 1999; 99:482-90), besides to confirm
such aspects of left ventricular dysfunction after thrombolysis and coronary
angioplasty, stressed the role of alpha-adrenergic blockers in reducing the coronary
vasoconstriction and improving the left ventricular dysfunction post-ischemic. In the
myogenic theory point of view, the left ventricular dysfunction recorded in this way is
preconized as a primary process.
Also, the paper from Tamura, K et al (Am Heart J, 1996; 131:731-5) reported
successive echocardiographic and electrocardiographic recordings in UA showing
myocardial aspects of RMI + RVI which concepts are inside of the MT; If they have
applied the cardiotonic during their study, they certainly had the record of immediate
clinical and physiological stop of UA.
We need to emphasize the paper from Murakami, T et al (Am J Cardiol, 1998; 82 :839-
44) about its new methodology represented by aspiration thrombectomy after
thrombolysis, showing that intracoronary thrombus is absent in a substantial number of
patients with acute myocardial infarction. We have the impression that once more the
TT have lost its support about the coronary thrombosis in the AMI when these authors
came to strengthen our concept of primary myocardial infarction and secondary
coronary thrombosis. Their findings after thrombolysis indicate: Recent thrombus
(49%), Without thrombus (30%), Atheroma (14%), Organized thrombus (2%) and Not
defined thrombus (5%).
Finally, we have to stress the study by Steven Smart et al (Am. Heart J., 1997; 133:
822-834) showing, during the echocardiography detection, successive effects over the
ventricular dysfunction developed by the AMI, and the reversible dysfunction of akinetic
and hypokinetic segments with the use of Dobutamine. Dobutamine, in the same
manner of cardiotonics, is a potent agonist of Beta 1 adrenergic receptors, improving
the contractile left ventricular function in AMI, due to its inotropic effect. These findings,
in our point of view, are perfectly compatible with the Myogenic Theory of AMI and
consequent and obligatory treatment by cardiotonics as defended by us since 1972.
No doubts that all ways go to the complete demonstration that cases normally
submitted to angiographic and ventriculographic studies arrive with the recognition of
conflicting aspects with the TT and compatible aspects with the MT.
Therefore, we will pass in review such aspects that must be considered as the
pathological reality of coronary-myocardiopathy which the Myogenic Theory Explains:
1) Roberts, WC (Circulation, 42:215, 1972 -- Full Text, free) showed that in cases of AMI
with early sudden death that coronary thrombosis occurred in approximately 10% of
cases with subendocardial infarction of left ventricle and in around 50% of cases with
transmural necrosis.
 MT explains: the recent findings by Murakami et al during the acute myocardial
infarction, confirmed and reinforced old pathological studies realized in the 1950
decade which were stressed by Roberts in 1972.
2) Spain, DM and Bradess, VA (Am J Med Sci, 1960; 240:701) showed total coronary
obstruction of atherosclerotic nature representing around of 75% of cases of AMI and
only 25% of cases with coronary thrombosis in autopsy, recorded during 25 years.
MT explains: in these cases the total coronary atherosclerotic obstruction was old and
the AMI was resulting from severe regional coronary-dependent myocardiopathy with
MRI + RVI and secondary coronary thrombosis not obligatory.
3) Spain, DM and Bradess, VA (Circulation, 1960; 22: 816) recorded the increase of
incidence of coronary thrombosis related with the increase of lifetime after AMI: < 1
hour = 16%, 1-14 hours = 37% and > 24 hours = 53%.
MT explains: these numbers represent a clear demonstration that AMI is primary and
the coronary thrombosis secondary, not obligatory and with slow formation.
4) Erhardt, LR et al (Lancet, 1973; 1:387; Am Heart J, 1976; 91:592) demonstrated the
coronary thrombosis incorporating fibrinogen marked by I-125 and I-131, radioactive
agents administered after 10-15 hours from the start of the clinical manifestations of
AMI, fact that suggests coronary thrombosis as consequence of primary myocardial
necrosis; and the record of the exclusion of I-125 in the thrombus of 1 case, when the
radioactive agent was administered 47 hours after the start of clinical manifestations of
AMI.
MT explains: the radioactive agents I-125 and I-131 incorporated to the fibrinogen in
the thrombus in progressive organization, not happened in the referred 1 case because
the thrombus was already formed.
5) Hellstrom, HR (Circulation, 1970; 42 (Suppl III) : 165) demonstrated in a experimental
manner, that AMI produced by surgical ligature of coronary artery without endothelial
lesion was responsible by the vascular stasis and the consequent coronary thrombosis,
recorded in the coronary artery after released.
MT explains: significant coronary thrombosis formed as consequence of vascular stasis
in the artery blocked by the AMI; such process is similar to the cerebral and cardiac
infarctions coincident with the use of anti-conceptives.
6) AMI coincident with rupture of atheromatous plaque and coronary thrombosis from
coronary artery related with the infarcted region.
MT explains: the coronary thrombosis watched in this way have been conveniently
interpreted by the orthodoxy as primary. However, the coronary thrombosis can come
late, subsequently to the AMI, whose rupture of the plaque should be provoked by the
invasion of white blood cells identified as inflammatory and by its derived products
providing the formation of coronary thrombosis.
7) Coronary arteries angiographically normal related with the infarction area without
coronary thrombosis.
MT explains: these arteries are widely compromised by the atherosclerotic process,
exclusive of wall, apparently canalized but inelastic, what modifies the circulation from
continuous to intermittent type which will endanger the dependent myocardium, taking
it to the AMI according to the MT model.
8) Case of UA interrupted by the cardiotonic, showing normal coronary arteries with slow
flow and defined assynergy of the coronary dependent myocardial region and with
increased systolic residual volume > (+/++); which, in the period of 2 years (still using
cardiotonic), evolved to the total obstruction of the left descendent anterior artery and
identical ventriculogram with systolic residual volume > (++), but without worsening the
clinical situation.
 MT explains: the use of cardiotonic + coronary dilator have guaranteed the
preservation of myocardial and symptomatic stability, in spite of the evolution of the
coronary arterial process to the total obstruction without evolving to the MI.
9) Bulkley, BH and Hutchins, GM (Circulation, 1977;56:906) published cases of AMI
situated in revascularized region by pervious coronary artery bypass, interpreted as
paradoxical infarction.
MT explains: in these cases the myocardial ischemic effects exist and the
ventriculographic aspects are useful to demonstrate that AMI is primary, even without
coronary thrombosis which we consider not obligatory.
10) Old atherosclerotic plaque totally obstructing the coronary artery related with the
infarcted region.
MT explains: cases of this type are useful to demonstrate that the compromised
coronary-dependent myocardium is taken to the RMI + RVI and to the AMI by
evolutionary and degraded coronary-myocardiopathy process.
11) AMI developed during the habitual or unusual practice of physical activities during or
immediate after the ergometric test, sex, sport or during the digestive period plus
physical efforts (even light), frequently happens in front of coronary arteries with not
significant, severe or even total obstructions by old plaques, simultaneous or not with
coronary thrombosis.
MT explains: in that cases the dependent coronary myocardial region compromised in
its structure can arrive to the AMI through an abrupt exhaustion of the myocardial
region – RMI + RVI – followed by coronary thrombosis.
12) The occurrence of AMI within 2-21 days after the abrupt interruption of beta blockers, in
continued use.
MT explains: due to its negative inotropic effect beta blockers develop generalized
hypotonia which eliminate the intersegmentary confrontation of the coronary/dependent
myocardium, with the effect of temporization but without to avoid the AMI neither other
complications like cardiac insufficiency and sudden death. Its abrupt interruption is
followed by the reestablishment of the intersegmentary confrontation owing to the
unprepared coronary/dependent myocardial region which takes to the UA with
manifestations of RMI + RVI, occurrence of AMI, cardiac insufficiency, severe
arrhythmia and sudden death.
13) Occurrence of AMI after the interruption of cardiotonic in continued use for the
preservation of the myocardial and symptomatic stability in chronic coronary-
myocardiopathy with or without previous myocardial infarction.
MT explains: the cardiotonic absence may lead to the myocardial intersegmentary
confrontation which may lead to the UA and consequently to the AMI, according the
model preconized by the MT.
14) Case of UA interrupted by the cardiotonic, showing the 3 coronaries - left descendent
anterior, right and circumflex – completely obstructed, but with a rich net of collateral
coronary circulation, and with left ventricular dysfunction but without recordings of
anterior infarction.
MT explains: This case came to confirm once more the immediate results of
interruption of UA in 100% of the cases (0% mortality), with the use of the new
therapeutical concepts of the MT. Treatment of attack followed by the permanently
upkeeping with the cardiotonic + coronary dilator has developed the return to the
myocardial stability that was preserved in this way and as prevention of myocardial
infarction.
15) Case of angina, permanent and with great suffering with repeated crises of UA,
resistant to all types of medication, lasting 9 months; happening 10 years after the
 myocardial infarction with total obstruction of the 3 epicardial coronaries – DAE, D and
CFx – ventriculogram with large increase of the cardiac area and characteristics of
hibernating Heart. He was attended in our coronary care unit during the UA crisis when
was submitted to the cardiotonic, recording immediate and complete relief. From this
moment on this patient remained under treatment with cardiotonic in a myocardial and
symptomatic stability during 13 years of comfortable survival, passing away with 73
years old, due to a cerebral stroke.
MT explains: this case was interpreted as a permanent deficient myocardial condition
mixed with symptomatic instability represented by crises of RMI + RVI finally
interrupted by the cardiotonic and therefore upkeeped for long survival.
16) Cases of chronic stable angina with the symptomatic and myocardial stability preserved
by decades, with or w/out previous myocardial infarction showing evolving coronary
atherosclerotic processes to the total obstruction of 2-3 coronaries w/out occurrence of
AMI.
MT explains: maintained by the cardiotonic + coronary dilator therapeutic since 1991
with the addition of ACE inhibitor, his future has been calm and guaranteed,
complementing in this way the effects provided by the collateral coronary circulation.
17) Cases of UA interrupted by the cardiotonic, maintained by decades, of patients with
significant obstructions of 2-3 coronaries have had evolution to total obstruction with
rich net of collateral coronary, without recordings of myocardial infarction, during the
long survival.
MT explains: Interruption of UA by cardiotonic as attack and maintenance treatment
have guaranteed the preservation of myocardial and symptomatic stability as well in
the prevention of myocardial infarction.
18) Cases generally admitted in coronary care units as with AMI were treated by
cardiotonic in our unit, showing ever clinical and enzymatic transformations which led
us to classify them as clinical infarctioning pictures, determined by the behavior of
enzymatic peaks.
MT explains: the cardiotonic in AMI has been considered as a myocardial protector
(Mesquita, 1973; Pizzarello et al, 1975 and Morrison et al, 1976.1980). Through the
enzymatic peaks the cases observed by us were distinguished in the following way:
1 - Myocardial infarction avoided: 20% of cases with normal enzymatic peaks or < 2x
the normal.
2 - Infarctioning clinical picture- interrupted: 47% of cases with enzymatic peaks < 3x
the normal.
3 - Infarctioning clinical picture- infarcted: 33% of cases with enzymatic peaks > 3x the
normal.
19) The method of Murakami et al using intracoronary thrombectomy aspiration and their
findings showing absence of coronary thrombus during acute myocardial infarction and
the use of transesophageal echocardiogram for the same purpose.
MT explains: the aspiration thrombectomy with thrombolysis and the echocardiography
can serve as support to the myogenic theory during the acute myocardial infarction,
offering to the pathologists the proof that coronary thrombus is secondary. Serve also
as a response to the paper of Chandler et al (AM J Cardiol, 1974; 34:823) about
coronary thrombosis and AMI simultaneous, indicating what is primary and secondary.
In Murakami method the thombolysis release the artery related with the myocardial
infarction while the aspiration thombectomy cleans the artery, stressing the left
ventricular dysfunction which can be corrected by the cardiotonic or by using the alpha-
adrenergic blocker as Gregorini et al.
20) Important findings in the acute UA about the incidence of intracoronary thrombus (52-
85%) since few hours after the start of symptoms until 2 weeks, while its incidence in
the chronic phase has been always low (0-12%).
MT explains: the echocardiography during the UA clearly shows the myogenic
mechanism recording the RMI which develops the RVI characterized by ECG,
coincident with platelet aggregates and inflammatory blood cells which invade the
involved region, becoming to the normal with the stop of crises.
21) Ambrose et al (Am J Cardiol, 1988;61:244-7) considered the myocardial infarction
without Q wave as an intermediary stage from UA to the myocardial infarction with Q
wave. They recorded total coronary obstruction in 26% of cases w/out Q wave and in
90% of cases with Q wave.
MT explains: the myocardial infarction w/out Q wave as intermediate stage to the
myocardial infarction with Q wave must be seen as favorable to the MT, and its
mechanism is considered by us as the preconized for the UA of long duration and in
smaller level than the reached by the AMI. So, in this case the myocardial lesion is less
stressed in subendocardial or subepicardial layers, and with low incidence of coronary
thrombosis.
22) DeWood, MA et al (NEJM, 1986; 315:417-23) recorded total coronary obstruction in
32% of AMI cases without Q wave and in a more detailed study showed an incidence
of total coronary obstruction significantly and progressively increased in relation with
the execution time of angiographic examination: 26% in 24 hours, 37% from 24-72
hours and 42% from 72 hours to 7 days. They also have recorded that the incidence of
subtotal coronary obstruction (> 90%), in myocardial infarction without Q wave, showed
evident reduction in gradual manner: 34% in 24 hours, 26% from 24-72 hours and 18%
from 72 hours to 7 days.
MT explains: These crescent indicators show that the formation of coronary thrombus
is secondary to the AMI depending directly of the evolution time of the infarctioning
process to become infarcted process; Evidently, the gradual reduction of indicators
referring to subtotal obstruction was observed contrary and parallel to the thrombotic
transformations recorded secondarily to the infarction.
23) Thrombolytics in UA improve the arterial events but show inefficiency about the clinical
events and regarding to stop the pathophysiological process, what led investigators to
recommend its use only in AMI. (Rentrop, P et al, 1981, Williams, DO et al, 1990,
Leinbach, RC, 1972, Freeman, MR et al, 1992, TIMI IIIA Investigators, 1993 and Chen,
L et al, 1997)
MT explains: These results came to confirm the failure of anticoagulants (1969) and
completed the tumble down of the TT what the orthodox cardiology pretends do not
happens.
24) Roberts, WC (Am J Cardiology, 1984; 97:1410) wrote: "When I have an acute
myocardial infarction take me to the hospital that has a cardiac catheterization
laboratory and open cardiac surgical facilities".
MT explains: in case of chronic coronary-myocardiopathy the preservation of
myocardial and symptomatic stability and prevention of myocardial infarction have
been guaranteed by the association of cardiotonic + coronary dilator + ACE inhibitor,
permanently. So, my advice to those which think like the grand teacher of pathological
anatomy represented by William C. Roberts, to defend their heart with calm using the
therapeutic efficacy by cardiotonics which complement the providential action of the
collateral coronary circulation.