The Myogenic Theory Explains

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.

II. III.

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 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 :83944) 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 coronarymyocardiopathy 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 alphaadrenergic blocker as Gregorini et al.

20) Important findings in the acute UA about the incidence of intracoronary thrombus (5285%) 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.