Early anti-apoptosis treatment reduces myocardial infarct size after a prolonged reperfusion

Objective: Significant myocardial apoptosis occurs in ischemia/ reperfused hearts. However, the contribution of apoptosis to the development of myocardial injury remains controversial. The present study attempted to obtain evidence that inhibition of apoptosis at early reperfusion can reduce myocardial infarction after prolonged reperfusion. Methods: Adult male rats were subjected to 30 min ischemia and 4 (apoptosis assay) or 24 h (myocardial infarction determination) of reperfusion and treated with vehicle, SB 239063, insulin or insulin plus wortmannin. Results: Treatment with SB 239063 or insulin markedly decreased myocardial apoptosis (10.6 +/- 1.5% and 7.9 +/- 0.9% respectively, P < 0.01 vs. vehicle) and significantly reduced infarct size (43 +/- 3.6% and 35 +/- 2.9%, respectively, P < 0.01 vs. vehicle). Most interestingly, inhibition of insulin signaling with wortmannin to block insulin signaling not only blocked insulin's anti-apoptotic effect, but also abolished its infarct reduction property. Conclusion: These data indicate that apoptosis contributes to the development of myocardial infarction, and inhibition of apoptosis at early reperfusion reduces the myocardial infarction.