To investigate and quantify the presence of apoptosis in early myocardial ischemia in humans.
Histologic sections from the left and right ventricles of 16 hearts with impending myocardial infarction were stained with terminal deoxynucleotidyl transferase-mediated deoxyuridine 5-triphosphate nick end labeling (TUNEL) method and with antibodies to p53, bcl-2, cpp32, FAS, FAS-L, and bax. DNA electrophoretic analysis was also performed.
According to the inclusion criteria, all 16 cases showed morphologic changes consistent with ischemia and/or reperfusion. TUNEL results were positive in 14 of the 16 ischemic areas. Unexpectedly, they were also positive in "remote from ischemia" myocardium of both the left and right ventricles. DNA electrophoretic analysis confirmed the results of TUNEL. Immunohistochemistry was uniformly negative, probably because of autolysis phenomena.
We showed that apoptosis precedes necrosis in humans, but the detection of apoptosis cannot be used as a diagnostic tool, since it can also be triggered by nonischemic events.