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 μM KB-R at the onset of reperfusion or before ischemia) were compared with controls (n = 12; ischemia-reperfusion 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-reperfusion. 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.