Myogenic Theory Explains!

Quintiliano H. de Mesquita qmesquita at HOTMAIL.COM
Fri Mar 5 06:35:06 EST 1999


Myogenic Theory Explains!

“The Thrombogenic Theory of Myocardial Infarction Tumbled Down and the
Ortodoxy Didn’t Have Noticed”

The ortodox cardiology stay repressed in their therapeutic behaviour 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 intervencionism 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,
represents a contradictory behaviour 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 ortodox 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 the cause and not consequence of coronary
thrombus. The myogenic theory met important support in pathological
anatomy findings since 1950 decade where the authors preconized the
coronary thrombus as consequence of acute myocardial infarction and not
its cause.

According the myogenic theory concepts the AMI is developed by
functional degradation state of the regional myocardial
coronary-dependent characterized by a pathophysiology essencially
myogenic, in the  3 stages of coronary-myocardiopathy:
- 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.
- 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.
- 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 ICP in avoided myocardial infartion,
ICP- interrupted myocardial infarction or characterized as ICP-infarcted
according the behaviour 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 uneffectives 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 about successive echocardiographical and
electrocardiographical  recordings in UA showing myocardial aspects of
RMI + RVI  which concepts are inside of the MT; If they had 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 the TT once more have lost its
support  about the coronary thrombosis in the AMI when these authors
came to strenghten 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%).

No doubts that all ways go to the complete demonstration that cases
normally submitted to angiographic and ventriculographic studies arrive
with the recognition of conflictant 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:

- Roberts, WC (Circulation, 1972;49:1) showed that in cases of AMI with
early sudden death that coronary thrombosis ocurred 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.

- 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
myocardiopathy coronary-dependent with MRI + RVI and secondary coronary
thrombosis not obligatory.

- 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.

- 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.

- 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 anticonceptives.

- 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 ortodoxy 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 inflamatories and by its derived products providing
the formation of coronary thrombosis.

- 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 intermitent
type which will endanger the dependent myocardium, taking it to the AMI
according the MT model.

- Case of UA interrupted by the cardiotonic, showing normal coronary
arteries with slow flow  and defined asynergy of the myocardial region
coronary dependent and with systolic residual volume increased  >
(+/++);  which, in the period of 2 years (still using cardiotonic),
evolved to the total obstruction of the left descendent anterior artery
and  ventriculogram identical with systolic residual volume  > (++), but
without worsening the clinical situation.
MT explains: the use of cardiotonic + coronary dilator 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.

- Bulkley, BH and Hutchins, GM (Circulation, 1977;56:906) published
cases of AMI situated in revascularized region by pervious coronary
artery bypass, interpreted as paradoxal 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.

- Old atherosclerotic plaque totally obstructing the coronary artery
related with the infarcted region.
MT explains: cases of this type are useful to demontrate that the
compromised coronary-dependent myocardium is taked to the RMI + RVI and
to the AMI by evolutive and degradated coronary-myocardiopathy process.

- 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 coronaries 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.

- 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 intersegmentar 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 arrhythmias and sudden death.

- 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 provides the myocardial
intersegmentar confrontation which may lead to the UA and consequently
to the AMI, according the model preconized by the MT.

- Case of UA interrupted by the cardiotonic, showing the 3 coronaries -
left descendent anterior, right and circunflex – completely obstructed,
but with a rich net of collateral coronary, and left ventricular
dysfunction but without recordings of anterior infarction.
MT explains: This case came to confirm more one time the immediate
results of interruption of UA in 100% of the cases and without
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 which develops the
return to the myocardial stability preserved in this way and as
prevention of myocardial infarction.

- 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 at 73 years old, due to a cerebral stroke.
MT explains: this case was interpreted as 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.

- Cases of chronic stable angina with the symptomatic and myocardial
stability preserved by decades, with or w/out previous myocardial
infarction showing evolutive 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 coronary collateral circulation.

-     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.

-    Cases generally admitted in coronary care units as with AMI were
treated by cardiotonic in our unit, showing clinical and enzymatic
transformations which led us to classify them as clinical infarctioning
pictures, determined by the behaviour of enzymatic peaks.
MT explains: the cardiotonic in AMI was 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 tyhe following way:
? Myocardial infarction avoided: 20% of cases with normal enzymatic
peaks or < 2x the normal.
? Infarctioning clinical picture- interrupted: 47% of cases with
enzymatic peaks < 3x the normal.
? Infarctioning clinical picture- infarcted: 33% of cases with enzymatic
peaks > 3x the normal.

- 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 and keep
away forever the TT in vivo, offering to the pathologists the prove 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.

- Important findings in the acute UA about the incidence of
intracoronary thrombus (52-85%) 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.

- 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
favourable 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.

- 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 for  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.

- 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 ortodox
cardiology make believe that do not happens.

- 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 all them
which think like the grand teacher of pathological anatomy represented
by William C. Roberts,  to defend their heart with calm using the
therapeutical efficacy by cardiotonics which complement the providential
action of the collateral coronary circulation.

Quintiliano H. de Mesquita, M.D.

For more information please visit my homepage at
http://www.infarctcombat.org/qhm/homepage.html
















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