Ischemic postconditioning (Post-C), brief cycles of myocardial ischemia and reperfusion during the early phase of reperfusion, is considered as a novel adjunct strategy to protect myocardium. However, the exact mechanism remains unclear and should be determined.

The hearts of male Wistar rats were subjected to 30 min ischemia and 2 hrs reperfusion. Control rats had no intervention either before or after left coronary artery occlusion. Post-C was elicited by 6 cycles of 10s reperfusioninterspersed by 10s ischemia immediately after onset of reperfusion. Subsets of postconditioning rats were treated with drugs as followings; naloxone (non-selective opioid receptor antagonist), naltrindole (a δ-opioid receptor antagonist), SB216763 (a glycogen synthase kinase 3β inhibitor, GSK-3β inhibitor), or atractyloside (a mitochondrial permeability transition pore opener, mPTP opener).

Post-C significantly reduced infarct size (15.9 ± 2.4%, P = 0.003) compared to control (29.9 ± 3.7%). The anti-infarct effect by Post-C was blocked by both naloxone (25.5 ± 3.9%, P = 0.044) and naltrindole (26.9 ± 2.3%, P = 0.022). Infarct size limiting effect by Post-C was also abolished by atractyloside (30.6 ± 3.6%, P = 0.003). In SB216763 with naloxone treated animals, the infarct size was decreased (17.4 ± 3.2%, P = 0.007) but not in SB216763 with atractyloside treated animals (27.4 ± 2.6%) compared to control.

These data suggest that Post-C may protect myocardium by inhibiting mPTP opening via δ-opioid receptor activation. GSK-3β is a downstream mediator of opioid receptors and an upstream mediator of mPTP opening in Post-C.