ACUTE MYOCARDIAL-INFARCTION IN HUMANS IS ASSOCIATED WITH ACTIVATION OF PROGRAMMED MYOCYTE CELL-DEATH IN THE SURVIVING PORTION OF THE HEART

Conditions of diastolic overload associated with increases in filling pressure trigger apoptosis, Moreover, ischemia alone and ischemia foll owed by reperfusion induce programmed cell death in myocytes in vitro, On this basis, the possibility was raised that apoptotic myocyte cell death may occur in the surviving myocardium acutely after infarction, Myocardial samples were obtained from the region adjacent to and remo te from infarction in patients who died within 10 days from the initia l clinical symptoms. Apoptosis was measured quantitatively by the term inal deoxynucleotidyl transferase assay and confirmed biochemically by DNA extraction and agarose gel electrophoresis. This analysis include d 20 infarcted and ten control hearts. DNA strand breaks in myocyte nu clei were observed in all 20 infarcted hearts in both the regions bord ering on and distant from the necrotic myocardium. However, the number of apoptotic nuclei was greater in the peri-infarcted region than in that away from infarction. Quantitatively, 12% of myocytes in the bord er zone showed DNA strand breaks, whereas 1% of cells were undergoing apoptosis in the remote myocardium, Moreover, DNA laddering was detect ed biochemically in these two regions of the heart. Thus, apoptosis ap pears to be a significant complicating factor of acute myocardial infa rction increasing the magnitude of myocyte cell death associated with coronary artery occlusion. (C) 1996 Academic Press Limited