BACKGROUND: Ischemic postconditioning (IPOC) has been suggested to reduce ischemic reperfusion injury. It remains unclear whether the activation of phosphatidylinositol 3 kinase (PI3K)/Akt is a causal mechanism in the cardioprotection afforded by IPOC, which was examined in the model of percutaneous transluminal coronary angioplasty (PTCA) minipigs. METHODS AND RESULTS: Minipigs underwent 45-min occlusion of the left anterior descending artery and 24-h reperfusion by PTCA. Postconditioning was elicited by three cycles of 30-s reperfusion followed by 30-s ischemia at the onset of reperfusion. Infarct size was determined by triphenyl tetrazolium chloride staining after 24-h reperfusion, and mRNA and protein expression levels of PI3K were ascertained by reverse transcriptase-PCR and western-blot analysis in biopsies. Infarct size was significantly reduced and myocardial PI3K (Akt and GSK-3β) phosphorylation was significantly increased with IPOC treatment compared with ischemic reperfusion. The administration of the PI3K inhibitor wortmannin (30 µg/kg) attenuated the protection of IPOC in the infarct size and decreased the expression of Akt and GSK-3β phosphorylation compared with IPOC. IPOC had no impact on mRNA expression of AKT and GSK-3β. CONCLUSION: Our findings show that IPOC is capable of protecting the myocardium against IR injury in the PTCA minipig model. The PI3K/Akt-signaling pathway is involved in the cardioprotective effect of IPOC.
BACKGROUND:Ischemic postconditioning (IPOC) has been suggested to reduce ischemic reperfusion injury. It remains unclear whether the activation of phosphatidylinositol 3 kinase (PI3K)/Akt is a causal mechanism in the cardioprotection afforded by IPOC, which was examined in the model of percutaneous transluminal coronary angioplasty (PTCA) minipigs. METHODS AND RESULTS: Minipigs underwent 45-min occlusion of the left anterior descending artery and 24-h reperfusion by PTCA. Postconditioning was elicited by three cycles of 30-s reperfusion followed by 30-s ischemia at the onset of reperfusion. Infarct size was determined by triphenyl tetrazolium chloride staining after 24-h reperfusion, and mRNA and protein expression levels of PI3K were ascertained by reverse transcriptase-PCR and western-blot analysis in biopsies. Infarct size was significantly reduced and myocardial PI3K (Akt and GSK-3β) phosphorylation was significantly increased with IPOC treatment compared with ischemic reperfusion. The administration of the PI3K inhibitor wortmannin (30 µg/kg) attenuated the protection of IPOC in the infarct size and decreased the expression of Akt and GSK-3β phosphorylation compared with IPOC. IPOC had no impact on mRNA expression of AKT and GSK-3β. CONCLUSION: Our findings show that IPOC is capable of protecting the myocardium against IR injury in the PTCA minipig model. The PI3K/Akt-signaling pathway is involved in the cardioprotective effect of IPOC.