Unknown in English Media View on Mechanisms and Management of Acute Myocardial Infarction

Unknown in English Media View on Mechanisms and Management of Acute Myocardial Infarction
Yabluchansky Mykola (Nikolay)
Internal Diseases Dept. of School of Fundamental Medicine of Kharkiv Karazin National University (Ukraine)

The object of this publication is to present unknown in English media my understanding of acute myocardial infarction (AMI), that was developed at last two decades of previous century. This understanding is based on insight on AMI as one of types of acute inflammation.
Definition
AMI is a disease or a clinical syndrome accompanying other diseases, which is represented by acute coronarogenous aseptic inflammation of the part of a heart wall, and clinically correlates with stress reactions of body control systems and is determined by the extent, localization, nature, and stage of structural transformations in the infarction zone, as well as circulation changes, and their consequences.
'Myocardial infarction is coronarogenic myocardial necrosis', this inaccurate formulation travels with small variations from one book to another.
In terms of pathology, it may still be true. Though, even there, it is far from being accurate - infarction equals myocardial necrosis only if an inflammation reaction is absent and a necrotic tissue is never substituted with the granulation one. So, a patient dies early. But what we can say about the rest of patients? Is it not infarction any more? For example in case a patient dies during sub acute period AMI only granulations are found in the place of necrosis [1].
Everybody agrees that AMI goes clinically through the most acute, acute, sub acute, and post myocardial infarction periods. This is reflected in circulatory disturbances in the infarction zone, ischemia, first still reversible, then irreversible, necrosis, and the connective substitution of a necrotic myocardium with cicatrisation (of course, through inflammation, what can be the other way?) [3, 13, 15]. And it everything is tinted (and how) with stress-intermediary systemic reactions, secondary disturbances of biomechanics of heart functions, and intracardiac and central hemodynamics [9, 11, 12].
It is clear that this definition reflects the heart of the matter.
Etiology
As follows from the definition of AMI, it develops, when local coronary circulation disturbances as a triggering mechanism cross the time threshold and make the ischemia irreversible. Strictly speaking, acute ischemia that already crossed the threshold is just the formal cause of a further chain of events that results in pathology and the clinical picture of the disease.
All other causes are the sources not of AMI itself, but of the above mentioned 'local' triggering mechanism.
Mechanisms
The mechanisms of AMI should naturally be examined at systemic and local levels. They were selected by evolution. They are aimed at providing most favorable of possible courses of the disease [22]. Therefore, its complications can be understood only in terms of philosophy of failure of these mechanisms.
We should pray that, as often as possible, AMI followed mechanisms established genetically and selected by Nature. And the number of disturbances in them was as small as possible.
Systemic level
The response of organism systems to AMI is realized through stress and clinically manifests itself as brain mediated sympathetic activation and increased functional activity of a hypothalamic-pituitary an adrenal system with the change of functions of all target organs. For a favorable course and outcome of the disease, all other conditions being equal, an adequate organization of stress (eustress) becomes of primary importance.
Stress is switched on at the very beginning of ischemia. Its causes are different. These are changes in the interception of blood vessels and tissues in the infarction zone. It is also the entry of metabolic products from the infarction zone to the systemic circulation. Spasms of pain, sympathetic activation, hormones entering blood, blood leukocyte reactions, hyperdynamic circulation are the first manifestations of the stress [5, 19]. The pain signals an emergency. Besides, it makes the patient forget all other problems to devote attention to his health in real earnest.
Leukocyte reactions are important for the further development of the process, though they are usually considered to be of secondary importance. These reactions are triggered by the ejection of leukocytes from the depot to the systemic blood flow. Since the depot mainly contains neutrophils, leukocytosis appears as the shift in cell count, neutrophils are activated and migrate to the infarction zone by positive chemotaxis. Infarction zone products getting in the blood flow play the role of attractants for them. The activation of neutrophils appears as hyperenzymemia (transaminase, etc.), higher contents of eicosanoids, leukotrienes in particular, protein-carbohydrate complexes, and other biologically active agents.
Stress is changing as the process develops. Nervous and humoral regulations are regained. Leukocytosis declines, and the leukogram changes. Granulocyte counts decrease, and their functional activity is suppressed, while agranulocyte counts and their activity increase. The structural change of the leukogram is the result of controlling effects of infarction zone products getting in the blood flow. Thus, neutrophil decay products from the infarction zone are repellents for neutrophils and attractants for agranulocytes. An enzyme level in blood falls, while the proteins and protein-carbohydrate complexes content grows. These are the systemic manifestations of an inflammation process in the infarction zone. Thus, even such a special case as hyperfibrinogenemia is not a sign of the activation of blood coagulation system but is the evidence that the situation with AMI takes a satisfactory turn. Here, it is important to remember that great hopes, placed in anticoagulant therapy, were not justified. These lost hopes cost life to many patients. It was long ago…
With the termination of an AMI phase, regulation problems disappear and not a trace remains of the stress. I would ask to take notice of the fact that we speak of a natural uncomplicated pathologic process.
Local level
The local level is the heart. The components of a pathologic process at the local level are not only changes in the infarction zone and recovery of heart shape and sizes but also adaptive changes of biomechanics of heart functions.
Infarction zone
Here everything is clear. All that happens is inflammation. Special, aseptic, alterative but still inflammation.
Let us look at phase processes. The first one is ischemia, reversible myocardial changes. Strictly speaking, it is the precursor of AMI, the state of pre-infarction. It is fully reversible . But if…. AMI, of course.
The transfer to irreversible changes marks the onset of necrosis. Necrosis is a lesion. General pathology teaches that in the location of the lesion there is always inflammation [2, 3, 16]. The lesion is the cause of inflammation. Thus, with the transfer from ischemic changes in the infarction zone to the necrotic ones, the inflammation starts in accordance with its traditional scheme. The necrotized myocardium undergoes destruction, and decay products are removed through the peri-infarction zone. It is specifically destroyed by neutrophil getting by chemotaxis from blood into the infarction zone and producing cathepsins. Their migration rate is rather high, about 2-4 mm per hour. It is easy to calculate that even the largest possible infarction is infiltrated by neutrophils in 6 hours at the most. At the same time, fibroblast precursors enter the infarction zone and the recovery process begins. It is impossible to separate necrotic and recovery processes, to look at them as the individual ones. They are synchronized and interconnected not only at the level of the infarction zone itself but also at the systemic blood level.
An absolutely false view raised to the level of dogma exists: necrotic and recovery processes in AMI are separated, the recovery processes following the necrotic ones. If this were true, all patients would be dead. Most likely, because of heart rupture. If not because of heart rupture, then because of acute vast aneurysm, for sure.
Necrosis is destruction, tissue gangrene [16]. The tissue loses its functions, not only contractile characteristics but also strength properties [4]. If infarction were necrosis, the heart wall in the infarction zone would have raveled out as a rotten shirt. But it does not happen in the case of an uncomplicated process. The strength properties of the myocardium in the infarction zone do not decrease. Moreover, for various reasons they even increase during the acute period. The retained strength of the heart wall in the infarction zone demonstrates that infarction in survived patients is not necrosis but inflammation accompanied with synchronized necrotic and reparative processes.
The result of a natural inflammation course in the infarction zone is the formation of a full-fledged scar in the place of necrosis. Maturation of a granulation tissue results in its consolidation followed by a decrease in infarction zone sizes. Depending on conditions, they can decrease by 25% or more.\ We should remind those who want to strongly intervene in the infarction zone that the phenomena occurring there (inflammation, compensatory and adaptive responses) are protective reactions originated as the result of evolution. On the whole, it is clear. We may intervene but carefully.
Peri-infarction zone
Systemic mechanisms and the infarction zone are interconnected through the peri-infarction zone, first of all, through its microcirculatory bed. Wastes from the infarction zone are removed through it, and the products necessary for reparative processes enter there the same way.
The larger the infarction–peri-infarction zone interface, the better the mutual effect of the infarction zone and systemic control. The peri-infarction zone cannot be smaller than that required for uncomplicated healing of the infarction zone [1, 5]. Therefore all the efforts to restrict it were doomed to failure.
Heart shape and size
In the case of infarction, a part of a mycrocardium becomes disabled. Disabled forever. And the functions of this part should be compensated. Hypertrophy of an intact myocardium develops. Healing of the infarction zone accompanied with the consolidation of scar leads to a decrease in its size. At the same time, corresponding changes occur in the intact myocardium [4, 9]. The heart shape is remodelled in such a way that its anatomic proportions are restored to favour its pumping functions. In the best case, the traces of infarction are difficult to reveal, even after thorough investigations.
Heart biomechanics
As everything, it is governed by processes controlling the course of the disease. During early phases, poststress rigidity of an intact myocardium is developing as a response to stress. Diastolic filling of ventricles diminishes, and the heart force drops. Minute blood volume is maintained by an adequate heart rate growth. A drop in ventricular ejection, along with regulatory effects on vascular tension mediated by stress, result in a decrease in peripheral resistance. The heart load decreases. As a result, biomechanics is improved and a sufficient systemic blood flow is maintained. In the case of an uncomplicated process we cannot find defects in this system as well.
Complications
Frequency
AMI is a complex and vulnerable process. In the most optimistic estimations, its complications are observed somewhere in a quarter of cases [10, 14, 22]. Of course, if it is diagnosed and treated correctly.
Immediate cause
Lets start with predisposing factors. However many we can name, all of them hit one target. The immediate cause of complications is inadequate stress. In other words, distress. Have little patience, and we would see how distress is realized as complications.
Risk factors
AMI can happen in a practically healthy person. Then, there is a good chance that it would take a favorable course. If such serious factors as vast infarction zone size, involvement of a cardiac conduction system and serious cardiac rhythm disturbances do not appear.
Vast infarction determines hyperreactive distress with possible torpid phase of true cardiac shock, or it causes an initially hyporeactive course, most likely with a short and therefore missed hyporeactive phase. Small infarction induces systemic wave reactions, and there is danger of its spread.
But it is not all. Even under most favorable conditions, a natural cataclysm (e.g. magnetic storm at the Sun) may happen, and as a result, stress out steps the limits of adaptive changes.
Risk of complications is higher in young and elderly persons. The coronary system of young patients is not trained, thus, vigorous stress reactions are highly possible, and it is not so difficult for them to turn into hyperreactive distress. On the contrary, elderly patients have problems with regulatory processes and, thus, with sufficiency of stress.
The following previous diseases are of great importance: diabetes mellitus, arterial hypertension and hypotension, immunodeficiency, particularly in the form of chronic immunopathologic processes. The above and other predisposing factors are multiplied in their interaction in such a way that the effect of sum exceeds the sum of effects. Comments are needless.
Standard mechanism of complications
We would remind that the cause of complications is distress. It is hyperreactive, hyporeactive or intermittent. The mechanism of complications, irrespective of a distress type, is always the same, viz. desynchronization of necrotic and reparative processes.
Desynchronization of necrosis and reparation leads to the loss of heart wall strength in the infarction zone. It is but a step from here to the stretching with cardiac aneurysm or heart rupture outcomes. 'High arterial pressure is a threat of rupture', we are frightened. The threat, of course, if the heart wall strength in the infarction zone falls to a critical level.
The strength of a heart in the case of uncomplicated myocardial infarction as in healthy people is 'a hard nut to crack', even for the highest pressure. Since biomechanical properties of the infarction zone differ from those of the intact myocardium, healing of the infarction zone is complicated not only due to the loss of heart wall strength but also due to the concentration of stresses along its boundary. Their magnitude grows when other unfavorable factors are superimposed. Thus, the areas of marked curvature of inner heart ventricular surfaces (transition of an interventricular septum onto other ventricular walls, transition of ventricular walls onto papillary muscles, etc.) are anatomic stress concentrators. If the infarction zone boundary is close to such a concentrator, the loss of strength contributes to its easier rupture. Major factors of stress concentration along the infarction zone boundary that contribute to its rupture.
Hyperreactive distress is excessive activation of all its determining systems. The result is intensive and rapid migration of polynuclears to the infarction zone. Necrosis and destruction are accelerated. Reparative processes lag behind. There is the desynchronization. If the infiltration of polynuclears to the infarction zone is excessive, their decay products retard the entry of reparative agents. In such cases a pathologist finds classical myocardial infarction: nothing but coronarogenic necrosis. Fast destruction of myocardium in the infarction zone has one more consequence, viz. high concentration gradients of all products formed in it along the boundary with the peri-infarction zone. Why not a condition for the electric instability of a heart? As a result, arrhythmia.
In the case of hyporeactive distress, everything develops slowly. Systemic reactions are sluggish or are absent at all. Thus, there are problems with the infiltration of polynuclears to the infarction zone. As a result, the necrotic phase is slow, which leads to the delay of reparative processes and their slow development. So, the desynchronization.
Hyperreactive distress leads to more commonly seen arrhythmia, earlier cardiac aneurysm and heart rupture. Hyporeactive distress with a sluggish disease pattern determines large sizes of aneurysm. As a rule, heart rupture occurs in the thinnest area of aneurysm.
- 'Intermittent distress, what happens?'
- 'Superposition of the above mechanisms by the formula: 'out of the frying-pan into the fire'. Everything becomes much more dangerous.'
The result of healing complications accompanied with distress of any type, as it was already mentioned, is aneurysm (acute and chronic, naturally) and heart rupture. They happen earlier upon hyperreactive distress but cover much larger areas in other stress cases. Acute aneurysm is most often acute cardiac insufficiency, and chronic one is chronic cardiac insufficiency. It is difficult to imagine heart rupture without cardiac shock. Arrhythmia upon hyperreactive distress, especially in the hyperreactive phase of intermittent distress, is quite natural.
During subendocardial myocardial infarction, healing complications with retarded necrotic processes are ready to turn into thromboendocarditis. Just dare say that it is not a patch, protection from the loss of strength in the infarction zone? Thrombus formation disturbances give rise to thromboembolism [5].
We can continue this topic. But it is already clear that the share of healing complications is growing like a 'snow ball' in the complications of the disease in general.
Compensatory processes
AMI is a disease or a clinical syndrome accompanying other diseases. All that occurs simultaneously with infarction is highly pathologic but not physiologic. But it, in terms of Voino-Yasenetsky's philosophy [2], corresponds to current requirements and, therefore, is normal. Inflammation, the typical pathologic process underlying the disease, is just that by definition.
Let us remember transitional atrial flutter accompanying large acute myocardial infarction. Whatever they say, a decrease in heart preload is an extremely precise mechanism. Of course, if this arrhythmia is normosystolic, and what is more, at a rate within upper limits of the norm. Try to restore sinus rhythm in such a patient, and his heart would start to 'choke'. Have you ever met such a situation?
We have already discussed compensatory functions of naturally formed thromboendocarditis. But if this process is disturbed? Of course, when we actively intervene in blood coagulability with the purpose of treatment. Or let us remember coronaroactive drugs for improving the blood supply in the peri-infarction zone. It appeared that they robbed it. Simply, because Nature did it the way that in the case of infarction, the vessels of the infarction zone are dilated as much as possible. There is nowhere to dilate them any more. We administer coronaroactive drugs and dilate the vessels of an intact myocardium. Blood flows out of the peri-infarction zone. It is an old story.
The conclusion is simple. Before improving something, one should first think for a while. And no more than that.
Clinics
Uncomplicated and complicated AMI’s are entirely different phenomena. We have good reason to make such a conclusion. Uncomplicated infarction is an evolution-selected and practically realizable strategy of the best healing of the infarction zone with the most qualitative recovery of a patient. Complicated infarction is the result and manifestation of disturbances in the realization of this strategy [6, 7]. Its clinical picture is different. And the clinical picture of uncomplicated infarction is a standard for its complicated forms [5]. If so, lets start with the standard.
Uncomplicated acute myocardial infarction
Just because it is uncomplicated, it does not create problems either for a patient or for his doctor. Of course, there are clinical manifestations of stress and the local processes described above (at the level of the infarction zone and heart as a whole). There is no getting away from them, myocardial infarction nevertheless.
The clinical picture of uncomplicated healing: pain is rapidly reduced by rather moderate measures, and higher levels of hormones, leukocytes, enzymes, proteins, protein-carbohydrate complexes in blood accompanied with phase changes correspond to infarction zone size (not very low and not excessively high, just fit perfectly well). The spectral analysis of cardiac rhythm demonstrates its tendency to metronomization with the redistribution of regulatory effects in favour of humoral immunity and a sympathetic nervous system. However, heart rate variability increases very soon, and the contribution from parasympathetic regulation also grows. An enzyme level reaches its maximum by the 18th hour from the beginning of the AMI and then decreases regularly. A level of protein-carbohydrate complexes starts growing from the 2nd day and reaches its maximum no later than by the 5th day. Blood analysis: moderate leukocytosis with neutrophilia that in a day gives place to constantly growing agranulocytic reactions.
All this is the evidence of satisfactory control and synchronized necrotic and reparative processes in the infarction zone. As the saying goes, we are waiting for a good scar in the place of necrosis. The electrocardiogram exhibits AMI signs but with expected evolution: the ST segment rapidly returns to the isoline.
Ultrasound reveals segmental disturbances of myocardial contractility, but the thickness of the heart wall in the infarction zone is retained. A heart rate increases, a stroke volume falls, but a minute volume is adequate to current requirements. Even if there are rhythm disturbances, they are perceptible only on the first or the second day at the latest. These extrasystolae are not dangerous and will not require any measures.
Patients feel well and become more active very early. Such behaviour not half worsens the prognosis, it favours more rapid recovery. Let us be honest, we often fear not the early activation of patients but our responsibility. And that is the most irresponsible treatment of the problem.
Complicated acute myocardial infarction
Though its clinical picture is rather diverse, certain regularities are evident. It would be unjust to lose the chance. Distress is the precursor of a trouble, therefore, this is far and away that we should establish its possible causes in a patient, determine the contribution from each of them.
A threatening sign of serious complications is a recurring, difficult-to-stop pain. Levels of hormones, leukocytes, enzymes, proteins, and protein-carbohydrate complexes in blood are growing. But those growths are insufficient or exceed any reasonable bounds. Phase changes are always associated with certain problems. They are too late or are taking such features… Their most degenerated forms are clear evidence of intermittent distress. Cardiac rhythm is metronomized, its rate falls rapidly. The contribution from humoral regulation to the energy spectrum is incommensurably growing. A parasympathetic component is suppressed almost completely. In the most serious cases, the result of metronomization is an equally low level or almost complete absence of all parts of the energy spectrum [8].It is white noise instead of regulation.
These changes appear long before other clinical complications and retain enviable stability. A level of blood enzymes reaches its maximum very early, during the first 12-14 hours, or with a considerable delay, in a day or more. In contrast to this, in both cases a level of protein-carbohydrate complexes starts growing with a delay, in four or more days from the beginning of the catastrophe. Blood exhibits undeveloped or excessive leukocyte reactions, without neutrophilia or with almost total predominance of neutrophils over cellular forms. The change from granulocytic to agranulocytic reactions as well as a growth of protein-carbohydrate complex concentrations is also late.
All these are clinical manifestations of desynchronization of necrotic and reparative processes. Heart rupture, acute or chronic aneurysm are not far distant. This implies an emergence of different forms of acute cardiac insufficiency, from true cardiogenic shock to cardiac asthma attacks, the development of chronic cardiac insufficiency. The electrocardiogram does not display any evolution of the ST segment, and only a frozen monophase curve is seen (naturally, in the most dramatic cases).
Ultrasound can easily reveal aneurysm, rupture of papillary muscles with valvular insufficiency, defects of an interventricular septum, other signs of complications of the major (inflammatory!) process in the infarction zone. Even if a heart rate grows, it cannot compensate a drop of a stroke volume under all circumstances. Regulatory systems can 'get frustrated’, and then a small ejection is multiplied by bradycardia. Patients can give bradycardic reactions instead of tachycardic ones.
The dilatation of cardiac cavities with the slowing down of intracardiac flows, especially in the case of clumsy intervention in blood coagulation systems is a good precondition for the disturbance of thrombogenesis (with thromboembolism).
Rhythm disturbances are another matter. They are resistant to interventions; they appear when they are not waited for, especially, as regards the states threatening the life of a patient. The clinical picture answering hyperreactive distress includes early rhythm disturbances.
Pathologic remodeling of heart chamber shapes during the formation of postmyocardial infarction aneurysm increases diastolic rigidity of a myocardium. Cardiac insufficiency becomes systole-diastolic.
The growth of stresses in a heart wall as the result of pathologic remodeling is the source of tardy persistent arrhythmia. It arises in the development of complications by any of possible mechanisms, but it should be treated carefully. Sometimes this is compensatory extrasystole, e.g. atrial flutter observed in critical patients.
Defects in the immune system controlling an inflammatory process in the infarction zone result in immunopathologic reactions by a Dressler's syndrome type.
It is easy to come to the conclusion that the specific feature of any clinical picture of complicated infarction in a patient is the deviation of the inflammatory process in the infarction zone from its natural course. The cause of this deviation is problems with regulation and interaction of regulatory systems with the infarction zone.
Differential diagnosis and prognostication
It is important to differentiate not only uncomplicated infarction from its complications but also among its complicated forms. It is even more important not to simply differentiate but to foresee them. Only in this case, we get the real opportunity to control the process, from simple observation to intervention with bringing to uncomplicated conditions. Criteria of differentiation and prognostication are summarized in Table 1. AMI with intermittent distress can start from any form cited in Table 1. These criteria are tentative and correspond to infarction zone sizes of about 10-20% of the corresponding camera.
Management of patients
The approach to a patient with AMI has its specific features. But how can it be otherwise? We are dealing with the catastrophe. Any catastrophe first of all implies the introduction of urgent measures, adequate in letter and in spirit. Naturally, everything is important, including regimen. And everything [5, 15, 18] should happen in good time.
Urgent measures
The very first urgent measure is naturally resuscitation, especially if a patient is in the state of clinical death. The next question: does his state satisfy the criteria (indications and contraindications) of thrombolytic therapy? If yes, it should be started as soon as possible [12]. Both resuscitation and thrombolysis exert a direct influence on regulatory systems, and we should always expect the transformation of eustress into distress in such patients if it were not already there. Resuscitation measures include adrenergic drugs activating stress. Successful thrombolysis accelerates the entering of infarction zone products in the systemic blood flow. This is a natural mechanism of activation of regulatory systems, therefore, stress increases as a rule. A postreperfusion syndrome is not only the evidence of successful thrombolysis but also the danger of the transfer from eustress, if the disease started in such a way, to hyperreactive distress with known consequences. Likely life-threatening arrhythmia is only an episode. But successful thrombolysis can additionally regulate control systems if the disease started with hyporeactive distress. On the contrary, it would have disastrous consequences if we cannot solved the problem of hyperreactive distress following thrombolysis [5, 22]. Urgent measures also include the control of pain. Pain informed about the catastrophe. But here its constructive role comes to an end. Further, it is only the overstrain of regulatory systems, thus, hyperstress and hypostress that follows it. By alleviating pain, we can reduce stress reactivity, transform hyperreactive distress into eustress, eustress into hyporeactive distress, or aggravate hyporeactive distress even more.
Thus, urgent measures require one to control the state of regulatory systems and to intervene in case of necessity bringing them to eustress conditions. Therefore on hyperreactive distress, narcotic and nonnarcotic analgetics, alpha and beta adrenoblockaders, nonsteroid anti-inflammatory agents are usually used. Upon hyporeactive distress, they are alpha- and beta-adrenostimulants, corticosteroids, leukopoiesis stimulants. Doses and administration periods are determined by the transformation of distress into eustress, activity levels in its approach to eustress parameters.
Regimen
At the very beginning of the disease, physical activity should be restricted. It is the necessary condition for ensuring mechanisms and processes to be effected for a favourable outcome of the disease. The first two days are sufficient time in the uncomplicated case. After that, physical activity is extended. You need not be afraid, the safety margin of a heart is high enough even as regards the infarction zone, and in these cases, it never drops below the level for a healthy person.
If there are prognostic signs of complications or the complications are present, physical activation is delayed. In the case of complicated acute myocardial infarction, the strength of the heart wall in the infarction zone decreases. Here early physical activation enhances the formation or extension of aneurysm, or possible heart rupture. But even in the worst cases, the time sufficient for the substitution of a granulation tissue for the necrotized one is no more than 12-16 days, thus, it is beyond reason to postpone activation till later. Everything should be done in proper time.
As regards the diet, its quantity and caloric value should be limited during the first days, divided into frequent small meals. It is important to follow digestion, avoiding constipation and meteorism. All this exerts a negative influence on the state of a heart, blood circulation, and regulatory systems.
Regimen is one of the most important components of patient management. We cannot diminish the importance of psychotherapeutic assistance. In this connection, we should emphasize the necessity of simple personal contacts that are always insufficient for a patient and that favour common success to a very great extent [7, 17, 20, 21].
Drug Therapy
The uncomplicated course of the disease does not require any measures. Only observation. In complicated cases, we cannot do without pharmaceuticals. Regulatory systems and processes, occurring in the infarction zone, should be brought to the state when the development of complications becomes impossible. A sudden decrease in the energy spectrum of heart rate variability and its parasympathetic component can be controlled by small doses of belladonna preparations. Upon a simultaneous decrease of a sympathoparasympathetic component, small doses of blockaders of an angiotensin-converting enzyme (ACE) are prescribed for long periods.
Upon hyperreactive distress and accelerated necrotic processes, our aim is to decrease the former and to retard the latter, using beta blockaders and anti-inflammatory drugs administered enterally and/or parenterally.
Hyporeactive distress and retarded necrotic processes require the prescription of alpha -and beta-adrenostimulants, bacterial and leukocytic pyrogens, leukopoiesis stimulants, using several ways of administration.
Upon intermittent distress, the attitude should be even more careful to prevent wave recurrence of necrotic processes.
As the optimization of distress of any type is approached, pharmaceuticals, promoting reparation in the infarction zone, should be added. These are leucopoiesis stimulants, steroid and nonsteroid anabolics.
If the therapy is optimized, clinical complications do not develop or are not so serious. It refers to possible heart rupture, acute and chronic aneurysms, giving rise to acute and chronic cardiac insufficiency, arrhythmia, and other complications.
When necrotic and reparative processes are seriously desynchronized and we cannot expect the complete restoration of synchronization, additional measures are necessary. We can try and prevent the development of aneurysm or the formation of a scar of large sizes, reducing terminal diastolic filling and postload on heart cameras. Here the choice is the combination of ACE blockaders with depot-nitrates and nitrites.
Special attention should be paid to patients with immunopathologic reactions and states to avoid the development of a postmyocardial infarction syndrome. Here immunomodulators would be useful.
If a heart rate does not exceed its upper level by more than 10%, with a decrease in peripheral resistance and cardiac output, sinus tachycardia is certainly of compensatory nature, and it should not be intervened. Our attitude to it should also be the same in the case of aneurysm development. Any intervention would be more detrimental. If it is necessary to intervene in tachycardiac reactions, this intervention should be administered in such a way that a decreasing heart rate would still be retained at the upper level of a physiological norm.
Rate disturbances, even if they are associated with the involvement of conduction system elements in the infarction zone, require careful treatment all the same. Diuretics prescribed for a short period would probably shorten the exudative phase of inflammation, and as a result, conduction would be improved. An external pacemaker would also be useful for a short time. It would solve the problem precisely, and this is inaccessible for any pharmaceuticals.
Extrasystole and paroxysmal tachycardia during the most acute and acute periods of the disease are the evidence of possible hyperreactive distress and accelerated necrosis. Their correction reduces risk and frequency of arrhythmia. In this case, beta-blockers are anti-arrhythmic drugs with a pronounced antistress effect.
Sinus tachycardia as well as other forms of arrhythmia can be not only pathologic but also compensatory. Extrasystole accompanied with pronounced bradycardia requires pharmaceuticals increasing a heart rate, such as atropine, belladonna preparations, etc. Arrhythmia accompanying the development of acute and chronic aneurysms is caused by high pressure of left ventricle filling. Anti-arrhythmic measures decrease heart preload and effectively reduce diastolic ventricular filling. Ectopic substituting rhythms are the problem of a sinus node. Therefore, one should think first before their suppressing. Normosystolic atrial flutter, suddenly appearing on cardiac insufficiency, causes a local decrease of heart preload. And probably, with the improvement of hemodynamic status, it would disappear by itself.
Direct anticoagulants should be treated with care. Surgeons know well that these drugs retard the healing phase of a wound process, and thus, the reparative phase of acute myocardial infarction. Those who went through the enthusiasm for direct anticoagulants remember that the main cause of the death of patients was associated with thromboembolic complications. It is quite clear; Nature always takes vengeance for clumsy steps, e.g., the development of uncontrollable disseminated intravascular coagulation. Nowadays this enthusiasm has disappeared. And we can see that from the results, thank goodness. Even after thrombolysis, it is better to exclusively use heparins followed by small doses of anti-aggregants that also exhibit an anti-inflammatory effect.
There is one more danger in using direct anticoagulants. AMI with the involvement of an endocardium is accompanied with thromboendocarditis. A forming thrombus is the additional and effective way of penetration of agents ensuring and maintaining inflammation, thus, more effective reparation in the infarction zone. The thrombus formed is also a 'patch', protection from possible aneurysm and heart rupture. Direct coagulants disturb thrombogenesis. In this case, bulky, unconsolidated thrombi are formed. Why they should not tear and become the cause of thromboembolic complications? There are many things to think about, especially if you use your own experience of patient management. Maybe, a thrombus absent in transmural myocardial infarction is the cause of aneurysm or heart rupture.
The problem of coronaroactive drugs as basic therapeutic means does not require any discussions. The times have passed when it was considered that they improved circulation in the peri-infarction zone and favoured its healing. Thus, they are used only in accordance with strict indications.
It is desirable to recommend to hypodynamic patients with an atonic anterior abdominal wall to administer laxatives for a certain period of time. In the case of meteorism, enteral adsorbents are good.
Conclusion, or the most important principles
Everything is good in its season, therefore any measure should be well-timed. You cannot afford to be late. The human organism possesses such remarkable properties that any newly initiated process, including AMI and its complications, is subject to external therapeutic effects only for a certain period of time. As soon as the process is self-organized, it stops to be subject to those effects.
One of physician's percepts is festina lente. Not in the sense that you should not be in a hurry to respond. But in the sense that you should not be in a hurry to modify some or other functions and processes. You should be a good hand in 'transferring' a patient from hypertensive crisis to hypotensive one, from tachycardia to bradycardia, etc., what is more with AMI. This is 'out of the frying-pan into the fire'. Rapid actions are necessary only in the case of the catastrophe or for the period of the catastrophe.
After finding new syndromes and symptoms in a patient, the first thing you should do is to think. Why this syndrome all of a sudden? Of course, everything that happens in the case of AMI is pathologic. Here we refer to Voino-Yasenetsky again [2]. He was quite right that an appearing syndrome, maybe, met the requirement of the situation and, therefore, is normal. On the whole, you should measure thrice but, maybe, you will not have to cut.
Many physicians prefer the parenteral administration of drugs. And it is good. Still nobody can live without preferences. But for catastrophic health disorders, all the processes in a patient develop not so quickly. And problems with a digestive system is most likely an exceptional case, thus, there are no grounds to refuse it credence in the transport of drugs to the blood flow. Why not give preference to enteral forms of drugs?
The most important thing in AMI as in any other disease is that it is the mechanism of withdrawal from the catastrophe. In a specific way, losing a part of a contractile myocardium and substituting it with a connective tissue through inflammation, or through other irretrievable losses. We have already discussed them. Nevertheless we have nowhere to go. We have to go through the disease. And the most important thing: it should take the best of all possible courses, i.e. the optimum course. The task of a physician is to lead a patient through the disease, to lead a patient with AMI through his own AMI. Here the best strategy is the optimization of complicated forms of the disease bringing them to uncomplicated conditions.
This strategy is based on the disease optimum principle [6, 7], in accordance with the latter, the optimum is minimum health resources spent for recovery.
Principle components as applied to AMI:
• identification of its optimum for a patient;
• determination of an extent and nature of its deviations from the optimum;
• verification of a diagnosis in accordance with the above;
• determination of the global target of the disease optimum as the best possible outcome with maximum full-fledged substitution of a connective tissue for the necrotic one in the infarction zone;
• treatment of a patient by bringing the disease to its optimum depending on a mechanism and extent of deviations as well as time of therapy initiation;
• solution of local problems by methods that do not contradict the global aim.
The optimum management of a patient with AMI is within power of a real physician.
References
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