The variable morphological coexistence of apoptosis and necrosis in human myocardial infarction: significance for understanding its pathogenesis, clinical course, diagnosis and prognosis.
BACKGROUND
Myocardial infarction includes both apoptosis and necrosis, but little is known of the morphological relationship of these two different forms of cell death in the human heart, despite the possibility that this may have clinical importance.


METHODS
Hearts from 77 cases of fatal myocardial infarction were examined. Twelve morphologically representative hearts were selected for immunohistochemical staining to define in detail the histology and cytology of apoptotic areas.


RESULTS
Both apoptosis and necrosis were present in every heart. Necrotic myocytes quickly disintegrate and evoke acute inflammation. Apoptotic myocytes retain their membrane integrity and do not evoke acute inflammation. Phagocytosis of apoptotic cells and apoptotic bodies occurred with engulfment by either neighboring myocytes or macrophages, but predominantly the latter. In many apoptotic areas, the phagocytic capacity was overwhelmed, resulting in large pools of apoptotic bodies lying free in the extracellular space.


CONCLUSIONS
Because apoptotic cells retain their membrane integrity, enzymatic diagnosis of myocardial infarction that is due to necrosis. Measurement of any intracellular enzyme consequently always underestimates the extent of myocardial infarction, often by a large margin. Morphological progression of cell death in myocardial infarction, from apoptosis to necrosis, may depend upon exceeding the local capacity for phagocytosis of apoptotic cells. However, cells dying by either apoptosis or necrosis are equally dead. There is a need for better definition of the role of apoptosis in myocardial hibernation (or stunning), in ischemic preconditioning and in the pathogenesis of silent angina, and post-myocardial infarction remodeling.
Department of Pathology, World Health Organization Cardiovascular Center, University of Texas Medical Branch, Galveston 77555-0175, USA.
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D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D017209:Apoptosis; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000175:diagnosis / Q000473:pathology*; D009206:Myocardium / Q000473:pathology*; D009336:Necrosis; D011379:Prognosis