Comparative Antiapoptotic Effects of KB-R7943 and Ischemic Postconditioning During Myocardial Ischemia Reperfusion

We examined whether KB-R7943 reduced infarct size by attenuating apoptosis during reperfusion and also compared antiapoptotic effects of KB-R7943 and IPost. For this purpose, isolated rat hearts underwent 30-min global ischemia and 120-min reperfusion. Ischemic postconditioning (IPost) (n?=?15; three cycles of 10-s reperfusion/10-s ischemia or three cycles of 30-s reperfusion/30-s ischemia) and KB-R7943 (n?=?15; 1???M KB-R at the onset of reperfusion or before ischemia) were compared with controls (n?=?12; ischemia?Creperfusion only). Myocardial injury was determined by TTC staining, TUNEL assay and caspase-3 activity. AKT and eNOS phosphorylation were measured by immunoblotting. We found that IPost (10?s), Pre KB-R, and Reperf KB-R reduced infarct size (29?±?4.1, 35?±?5.0, 28.6?±?3.4?%, respectively, vs. controls 46?±?8.7?%; P?<?0.05) and attenuated cell apoptosis (TUNEL-positive cardiomyocyte nuclei) in the myocardium (P?<?0.01). Moreover, IPost (10?s), Pre KB-R and Reperf KB-R significantly decreased caspase-3 activation caused by myocardial ischemia?Creperfusion. However, IPost (30?s) did not show any effect on necrosis and apoptosis. Akt, eNOS phosphorylation, at 30?min of reperfusion/IPost-10?s was significantly higher than other groups. In conclusion, KB-R7943 was as effective as IPost in reducing necrosis and inhibiting apoptosis and it might be an ideal pharmacological agent to provide a more amenable approach to cardioprotection.