Objective:Ischemic postconditioning has been defined as brief periods of reperfusion alternating with re-occlusion applied during the very early reperfusion. This study explores the potential of insulin to mimic ischemic postconditioning.

Methods:Langendorff-perfused rat hearts were subjected to 30 min. of regional ischemia and 120 min. of reperfusion. The hearts were randomized to either control (no treatment), ischemic postconditioning (Isch. Post: 3 x 30 s of global ischemia at the beginning of reperfusion), or insulin postconditioning (Ins. Post: 3 x 30 s infusion of 0.3 mU/ml insulin at the beginning of reperfusion). To investigate the potential involvement of Akt/PKB and p70s6-kinase in the insulin postconditioning group, blockers of the respective protein kinases [SH-6 for Akt/PKB and Rapamycin (Rap.) for p70s6-kinase] were co-administered with insulin. Infarct size/area at risk was measured using TTC staining and Evans Blue dye (0.2%), respectively, and presented as mean±sem.

Results:Exposing the isolated rat heart to ischemic- or insulin postconditioning significantly reduced infarct size (% of area at risk), compared to controls (Ctr. 49.6±3.0, Isch. Post. 17.7±4.1, Ins. Post. 22.9±4.6, p<0.001). Insulin postconditioning was completely abolished by inhibition of Akt/PKB and p70s6-kinase, using SH-6 and Rap., respectively (Ctr. 49.6±3.0, Ctr. SH-6 59.5±3.9, Ins. Post. + SH-6 47.5±5.3, Ctr. Rap. 46,63±3.19, Ins. Post. + Rap. 54.56±7.94, ns.)