Ischemic Postconditioning Inhibited The Myocardial Apoptosis After Cardiopulmonary Bypass.

Objective: In cardiovascular surgery field, how to protect the heart from ischemia/reperfusion injury during cardiopulmonary bypass is still an important and subsistent problem. Although a series of protection methods had been used during CPB, I/R injury still happen and is harmful to cardiac function. Previous studies for CPB focus on how to prevent injury from ischemia or hypoxia during cardioplegia. Little attention has been pay to how to protect the heart during reperfusion phase. Most of them were designed to evaluate some exogenous methods, such as temperature and components of cardioplegic solution and mode of medication. Recently, some endogenous cardioprective phenomenon has been introducted, like ischemia preconditioning and ischemia postconditioning, which brings new area to cardioprotective research. The present study was designed to determine whether IPost or IPC are protective against myocardial apoptosis after cardiopulmonary bypass on canines.Part 1Methods: Six canines underwent CPB with different aortic cross-clamping time to establish an stable CPB model. Immuno-histochemistry and Western-blotting was used to detect the activation of RISK pathway (p-Akt and p-ERKl/2). Apoptotic index of cardiomyocyte at baseline, aortic declamping and 90 minute after reperfusion were detected by TUNEL method.Result: A stable CPB model was established with 60mins ACC time on canines. As compared with baseline, p-Akt and p-ERK1/2 levels were significantly increased at aortic declamping and 90 minute after reperfusion. Apoptotic index of cardiomyocyte was also increased after ACC and reperfusion.Part 2Methods: Twenty canines undergoing CPB were divided into four groups. 1) control group: CPB, with 60 minute ACC time, only. 2) IPC group: IPC was performed before ACC with two circles of two minutes ischemia and three minutes reperfusion. 3) IPost group: IPost, was performed after ACC with three circles of 30 seconds ischemia and 30 seconds reperfusion. 4) IPC+IPost group: both of IPC and IPost were performed as described above. Immuno-histochemistry and Western-blotting was used to detect the activation of RISK pathway (p-Akt and p-ERK1/2) and apoptosis associated proteins expression (Bcl-2 and Bax). Apoptotic index of cardiomyocyte at baseline and 90 minute after reperfusion were detected by TUNEL.Result: IPC, IPost or both of them significantly increased p-Akt, p-ERKl/2 and Bcl-2 levels and decreased levels of Bax compared with the controls. All three treatments decreased apoptotic index of cardiomyocyte. All effects were similar among treated groups.Conclusion:1, CPB with 60 minutes ACC could cause myocardial apoptosis. CPB also could activate RISK pathway. But it was not able to reduce myocardial apoptosis caused by I/R injury.2, As an endogenous cardioprotective phenomenon, IPost could activate RISK pathway and regulate apoptosis associated protein Bcl-2 and Bax, reduce myocardial apoptosis after CPB.3, Cardioprotective effects were similar between IPC and IPost. The present results does not spport a combined effect for IPC and IPost.