Myocardial necrosis: The need for definition

Journal

of Molecular

and Cellular

Cardiology

LETTER

Myocardial

(1974)

TO

Necrosis:

6, 40142

THE

EDITORS

The Need for Definition

In both human and experimental conditions the term “myocardial necrosis” is used in a broad sense, often as synonymous of myocardial infarction. However, different histologic features suggest that the myocardial cell may die in different functional states. In fact the following three main types of myocardial necrosis can be observed in man: (a) the myocardial cell loses its contractility and seems to die in an atonic state. The earliest changes mainly involve the nucleus, while the registered order of the myofibrils is maintained even in the later stage of the repair process. The muscle fibres appear thinner as a result of passive overdistension. This type of necrosis-which is the fundamental lesion in a cardiac infarct-elicits an early exudation with centripetal polymorphonuclear leukocytic infiltration with subsequent wall damage and thrombosis of the vessels within the necrotic area (“coagulation necrosis”, Plate 1) ; (b) the myocardial cell dies in a hypercontracted state with early myofibrillar damage. The sarcomeres in the hypercontracted elements seem to clump together forming dense, anomalous, acidophilic cross bands alternating with stretched and broken myofibrils in the contiguous segments. No early nuclear changes, exudation, polymorphonuclear leukocytic infiltration, vascular changes are present. This type of myocardial damage characterizes many cardiomyopathies, particularly the myocardial necrosis in patients with pheochromocytomas and the experimental catecholamine-induced necrosis (“coagulative myocytolysis”, Plate 2) ; (c) an increasing intercellular oedema with dissolution of the myofibrils-without nuclear and vascular changes, inflammatory infiltration and anomalous contraction bands-appears to be the histological landmark of the myocardial cell dying in progressively failing state. This is the typical pattern found in the alcoholic cardiomyopathy with low output syndrome (“colliquative myocytolysis”, Plate 3). All three types of myocardial necrosis produce “alveolar” pattern, formed by intact, empty sarcolemmal tubes in which mononuclear cells and macrophages can be recognized. The healing process is accomplished by fibroblastic collagenization, without granulation tissue formation. Despite a common repair process, the clear-cut histologic difference in the early phase indicates that different pathogenetic mechanisms with different biochemical derangements may act in these three types of necrosis. If so, the same conclusion becomes obvious in discussing the pathogenesis of the coronary heart disease (CHD). In fact, in the external zone of acute coagulation necrosis and in the normal surrounding myocardium a more or less extensive coagulative myocytolysis is detected practically in all human cardiac infarcts. Furthermore in 67% of sudden coronary deaths, coagulative myocytolysis was the unique acute lesion. Histologic evidence

402

G.

BAROLDI

of colliquative myocytolysis was shown in 43% of the acute infarcts and in 10% of sudden deaths. The frequency and possible association of these three different patterns of myocardial necrosis in CHD suggest that the latter is a composite disease in which different mechanisms may interact. Particularly, coagulative myocytolysis even if focal-and therefore of little if any functional significance per se-may be the histologic sign of a sympathetic overstimulation in turn linked with ventricular fibrillation. A sympathetic overstimulation can result from many congenital and acquired factors, including the loss of contractility of an infarcted area. In the latter condition an increased function of the normal myocardium is expected to maintain cardiac dynamics in a normal range. At present a systematic ultrastructural study of human autopsy material can not be achievable. Therefore, a

further differentiation of myocardial cell death can not be excluded. However, despite limitations imposed by histological method, the recognition of different myocardial necroses implies a more precise correlation with clinical parameters and therapeutical approaches. Are there differences e.g., in electrocardiographic or enzymes changes with the different forms of myocardial necrosis ? What do we mean by an extension of an infarct ? In our experience it is not an extension of the coagulation necrosis but a coagulative myocytolysis involving the normal surrounding myocardium. Furthermore, while coagulative myocytolysis seemsto be a very important secondary event in the infarct cases, it appears a likely primary event in sudden coronary deaths, at least in many instances. In conclusion recognition of the different types of myocardial necrosis is essential to understand the natural history of cardiomyopathies in general and of CHD in particular, then a more appropriate therapy may be possible. G.BAROLDI Istituto Fisiologia Clinica, via S.A.V.I. 8, Medical School, University of Pisa, Italy

-

PLATE PLATE PLATE

1. “Coagulation 2. “Coagulative 3. “Colliquative

necrosis”. H & E x 450. myocytolysis”. PTHA x 450. myocytolysis”. H & E x 220.

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