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Book: Myogenic Theory of Myocardial Infarction - Part 8; Mesquita, QH de
Summary and Conclusions
The Myogenic Theory of the Myocardial Infarction, evolved through the traditional induction method had as its starting point the inefficiency of the anticoagulants in the prevention and treatment of infarction. This theory has been enforced by the successive reports of clinical conditions which cause infarction and do not conform to Herrick’s Thrombogenic Theory. It has also been propped by the anatomo-pathological findings of the dissenting group that purports coronary thrombosis as a consequence and not as cause of the acute infarction and, most of all, by the ever increasing literature on angiographically normal coronaries or pervious aorto-coronary anastomosis coinciding with acute infarction.
The Myogenic Theory commends a gradual deterioration of the ischemic myocardium, through repeated manifestations of relative coronary insufficiency and a reciprocal loss of contractility - a stage of symptomatic and myocardial stability - as responsible for the development of areas of progressive myocardial sclerosis: segmental myocardial disease.
Myogenic Theory Mechanism
The continued action of physical and psycho-emotional stressing factors which overwork the ischemic myocardium, or else of the pharmacological factors which depress the ventricular function and contractility, may cause the appearance of regional myocardial insufficiency and reciprocal myocardial ischemia - a stage of symptomatic instability or intermediate syndrome - spontaneously reversible and scarcely influenced by quick acting nitrites and nitrates, which is clinically alarming and foretells a nearing infarction.
At last, representing the apex of symptomatic and myocardial instability, there is the perpetuation of the symptomatic process as an infarction clinical picture, very serious and also evolutionary, without spontaneous reversion or immune to any kind of treatment but with cardiotonics. The following stage is the relentless passage to primary myocardial necrosis - acute infarction - and not necessarily to secondary coronary thrombosis. As regards the mechanism of the last, the post-infarction coronary stasis may be ascribed a prevalent role in its formation, or else it can be produced owing to edematous and cellular infiltration in the infarcted area; this includes the endothelial segments and can break and displace atheromatous plaques, which are inelastic, thus providing conditions for coronary thrombosis related to the damaged arterial wall; there would be characteristics clear of a primary process, but it would be only a sham primary coronary thrombosis.
In clinical practice, the finding of angiographically normal coronaries, or else stenotic but all the same pervious, in direct correspondence with the infarcted myocardial sector, has served the purpose of increasing the general misgivings as regards Herrick’s original concept. Besides, the myocardial infarction observed in the perioperative period of the aorto-coronary anastomosis, or else in a protracted period, has been recently very properly called paradoxical myocardial necrosis because it happens in areas of marked revascularization and showing pervious anastomosis.
The reciprocal is also true the absence of infarction is noticed in myocardial sites dependent on an artery with a total atherosclerotic obstruction; this fact represents the late condition of natural evolution of the atherosclerotic coronariopathy with the installation of the progressive segmental myocardial disease, frequently reported very much before the process of a clinical infarction picture, or else in cases of chronic coronariopathy undergoing the continuing action of cardiotonics.
According to the myogenic theory, there is no difference between the natural story of a chronic coronariopathy which winds up in an infarction or in a cardiac insufficiency; the variable lies only in the extension of the area of myocardial failing, which is limited to a myocardial segment only in the first case, being generalized in the other case.
The result of the predominance or else of the single manifestation of an injured coronary is very important as regards the ventriculogram. This is especially the case when there is involvement of the left anterior descending artery, which is responsible for the pathological lack of harmony and which causes an early myocardial infarction, a cardiac insufficiency, or a ventricular aneurysm. Whereas in 2 or 3 coronary arteries simultaneously injured the repercussion seems to characterize an apparent balance between each other and present a picture of pathological harmony of a slower evolution, they may evolve towards an infarction in the most injured section, or else towards a cardiac insufficiency. Thus, one admits a unitary mechanism for the physiopathology of both myocardial infarction and heart insufficiency in chronic coronariopathy, without the usual requirement of a primary coronary thrombosis in order to account for the occurrence of infarction. When there is an acute infarction, the regional myocardial failing causes at the same time a confrontation with the functionally normal ventricular segments, making it all the more grave and speeding up the process of primary myocardial necrosis - in heart insufficiency the failing is generalized and thus does not cause intersegmental confrontation, neither necrosis.
Works on experimental pharmacological studies have been responsible for the absolute contraindication of cardiotonics for acute myocardial infarction, as a result of their possible damaging action, owing to the increase of contractility and of oxygen consumption under conditions of a smaller oxygen supply.
Divulging such concepts generated a ban against cardiotonics on acute infarction cases. Nevertheless, clinical papers on the administration of cardiotonics in acute infarction, in spite of no experimental support, have been stimulating in their results, with absence of complications and a low mortality rate. These features oppose each other, but they are significant and sound, because the therapeutic results have consecrated them and should awaken the researchers to them.
The development of the myogenic theory on a new physiopathological basis is also based on a new therapeutic concept which differs from that held by orthodox cardiology and involves the debatable participation of the cardiotonic. Here our choice was endovenous strophanthin on account of our long clinical experience and an over plus of reasons owing to the great improvements registered in acute infarction complicated by heart insufficiency or tachyarrhytmias.
The initial clinical experience of using the cardiotonic in the intermediate syndrome corresponded wholly to our expectations, with prompt and sure results; the instability stage disappeared and there was a prompt return to the symptomatic and myocardial stability. The upkeep of these cases with an oral cardiotonic- digitalis or proscillaridin - in association with a coronary dilator has revealed itself calm and stable.
Going from the intermediate syndrome over to the behavior of patients usually considered as having an acute infarction: from the clinical, electrocardiographic and enzymatic point of view, face to endovenous G or K strophanthin provided daily for 6 days, remarkable aspects hitherto not seen were observed as regards its immediate effect on the ECG, clinical and enzymatic picture, without any complications; the behavior of the acute patients was effectively altered, and this constitutes a new experience, truly different. Owing to the obvious behavioral transformation in each case, they started to be called clinical infarcting pictures, a condition which may lead to infarction but which may also be interrupted and even avoided.
It became evident that the ECG, owing to the regressive tendency and to the frequent reversibility of the patterns as well as of the QS deflections, would thus represent only a diagnostic and topographic support but lacking conditions to hold precise prognostic information; a greater importance, concerning diagnosis and prognosis, would be held by the graded enzymatic reactions, which are favorably influenced by the cardiotonic, correctly representing the specific care for the critical physiopathological stage of the regional myocardial insufficiency - the precursor of primary myocardial necrosis.
Owing to the myocardial effects set forth through the enzymatic peaks, we can thus identify as an avoided infarction all cases with no registry of enzymatic repercussion; as an interrupted infarction those cases which show enzymatic peaks lower than three times the normal higher parameter, and as an infarction all those which excel this index.
The study of these results leads to the belief that the cardiotonic acts as a protector of the myocardium in the infarction clinical picture, because in this clinical condition there is predominance of the regional myocardial failure instead of the highly divulged post-thrombotic myocardial necrosis. Thus, the taboo concerning the use of cardiotonics in acute infarction of the myocardium is shown merely as a prejudice which does not correspond to facts.
A better placement of the cardiotonics has been lately reported as concerns experimental infarction, human infarction and chronic coronariopathy, by means of critical studies where the cardiotonics have a beneficial action, the ischemic myocardium being receptive; their effect is characterized by an increase of contractility both in the ischemic and the non-ischemic segments, without a higher oxygen consumption owing to the participation of other counterbalancing mechanisms.
The following conclusions were drawn from all the clinical experience applied to the study of the myogenic theory, within the physiopathological and therapeutic concepts:
1 - Coronary thrombosis is secondary and not mandatory; primary coronary thrombosis is exceptional.
2 - The experimental pattern of myocardial infarction does not seem to reproduce exactly the spontaneous human pattern.
3 - From the physiopathological point of view, the stable angina pectoris due to various factors is characterized by myocardial ischemia and loss of reciprocal contractility, whereas the unstable angina pectoris as well as the intermediate syndrome, both of them spontaneous, are caused by a mechanism inverse to the other, being thus characterized by regional myocardial insufficiency and reciprocal myocardial ischemia. The clinical infarcting picture represents the peak of symptomatic and myocardial instability, which is reversible only by means of a cardiotonic.
4 - The regional myocardial insufficiency is the critical stage of the physiopathology of infarction, still further compromised by the intersegmental confrontation, being followed by myocardial necrosis morphologically characterized by various stages.
5 - As regards chronic coronariopathy, the mechanism of myocardial infarction is identical with that of heart insufficiency, with only a difference in the extension of myocardial failure, which is regional in infarction and generalized in heart insufficiency.
6 - The cardiotonic, preferably strophanthin by endovenous route, represents the specific therapy at the stage of regional myocardial insufficiency. Its administration is apt to avoid infarction; at the phase of transition into primary myocardial necrosis it can be responsible for its interruption and, when necrosis is already under way, the infarction may be lessened, on account of saving myocardial fibers already ischemic but still viable.
7 - The cardiotonic increases contractility without increasing oxygen consumption owing to counterbalancing mechanisms: decrease of volume and of final diastolic pressure, as well as a decrease of tension of the ventricular wall.
8 - The cardiotonic used routinely in the infarcting clinical picture seems to have a protective action on the myocardium, which may be seen especially through following prompt effects.
9 - After resolving the intermediate syndrome and the infarcting clinical picture in chronic coronariopathy of stable or mute angina pectoris, the cardiotonic is mandatory and responsible for the functional preservation of the ischemic myocardium in a high level with the non-ischemic myocardium; thus there is no intersegmental confrontation in the long run; and even in the presence of total obstruction of 1,2 or 3 extra-mural coronary arteries by an atherosclerotic process, it prevents functional degradation of the myocardium and has avoided the infarction, always in association with a coronary dilator.
10 - The cardiotonic is responsible for an early and sure deambulation; in the infarcting clinical picture, with an arrested or avoided infarction, it takes place in the 5th day; in infarction it takes place in the 10th day, with discharge from hospital the following day; a 0,4% mortality rate has been observed in connection with early deambulation.
11 - Interruption of the cardiotonic in stable angina has coincided with an increase of symptoms and a decrease in tolerance to exertion; after the intermediate syndrome there have been relapses and even the occurrence of infarcting clinical pictures, especially when one changes to beta-adrenergic blocking.
12 - As regards the stable angina pectoris, the simultaneous administration of cardiotonic and beta adrenergic block has been responsible for the manifestation of symptomatic instability which disappears as soon as the beta-adrenergic blocking is withdrawn.
13 - When the cardiotonic is administered continuously there are sometimes manifestations of symptomatic instability which may call for a therapeutic reinforcement with strophantin, by endovenous route, in cases which are being treated with proscillaridin and digoxin or lanatoside-C, by endovenous route, or in those treated by oral digitalis; or else mere hospitalization and rest, without any alteration in the maintenance therapy; these measures having been taken there is an improvement in the clinical picture, with no enzymatic or electrocardiographic repercussion. It is curious that there are some coincidences with physical and emotional overloads, or infections of the upper respiratory tract preceding the increase of symptoms.
14 - The cumulative incidences of morbidity - heart insufficiency, intermediate syndrome and infarctioning clinical picture - and of mortality from angina pectoris, intermediate syndrome and infarctioning clinical picture, followed from 1972 to 1978, which were treated continuously with a cardiotonic together with a coronary dilator, are very low and contrast strikingly with the indices reported in literature as regards other forms of treatment.
15 - The compound administration of a coronary of a coronary dilator with a cardiotonic should not be overlooked. In the acute infarction process the absence of a coronary dilator coincided with the report of longer periods of pain, whereas there were no significant changes as regards other parameters.
16 - In the sample group of coronary arteriography in the intermediate syndrome and in the clinical infarcting picture, the material is practically identical as regards the features of injuries in general, in number and degree.
17 - In the clinical infarcting picture as well as in the arrested and in the avoided infarction, the frequent cases of total obstruction of the satellite coronary of the infarction region are interpreted as already existing, bearing in mind the support furnished by the low enzimatic levels. The total obstruction in infarcted patients cannot be discussed, but one can surmise that in a great number of cases it would also be already existant.
Author: Quintiliano H. de Mesquita, M D
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