Acute myocardial infarction in humans is associated with activation of programmed myocyte cell death in the surviving portion of the heart

Abstract

Conditions of diastolic overload associated with increases in filling pressure trigger apoptosis. Moreover, ischemia alone and ischemia followed 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 remote from infarction in patients who died within 10 days from the initial clinical symptoms. Apoptosis was measured quantitatively by the terminal deoxynucleotidyl transferase assay and confirmed biochemically by DNA extraction and agarose gel electrophoresis. This analysis included 20 infarcted and ten control hearts. DNA strand breaks in myocyte nuclei were observed in all 20 infarcted hearts in both the regions bordering 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 border zone showed DNA strand breaks, whereas 1% of cells were undergoing apoptosis in the remote myocardium. Moreover DNA laddering was detected biochemically in these two regions of the heart. Thus, apoptosis appears to be a significant complicating factor of acute myocardial infarction increasing the magnitude of myocyte cell death associated with coronary artery occlusion.