Modulation of cardioprotective effect of ischemic pre- and postconditioning in the hyperhomocysteinemic rat heart

Abstract

The present study was designed to investigate the effect of hyperhomocysteinemia (Hhcy) on cardioprotective potentials of ischemic preconditioning (IPC) and postconditioning (IPost). Rats were administered L-methionine (1.7 g/kg/day orally) for 4 weeks to produce Hhcy. Isolated Langendorff-perfused normal and hyperhomocysteinemic rat hearts were subjected to global ischemia for 30 min followed by reperfusion for 120 min. Myocardial infarct size was assessed macroscopically by volume method using triphenyltetrazolium chloride staining. Coronary effluent was analyzed for the release of lactate dehydrogenase (LDH) and creatine kinase (CK) to assess the degree of cardiac injury. Moreover, oxidative stress in the heart was assessed by measuring lipid peroxidation, superoxide anion generation and reduced glutathione. Ischemia-reperfusion (I/R) was noted to produce myocardial injury, as assessed in terms of increase in myocardial infarct size, LDH and CK in coronary effluent and oxidative stress in normal and hyperhomocysteinemic rat hearts. In addition, the hyperhomocysteinemic rat hearts showed enhanced I/R-induced myocardial injury with a high degree of oxidative stress in comparison with normal rat hearts subjected to I/R. Four episodes of IPC (5 min each) and six episodes of IPost (10 s each) afforded cardioprotection against I/R-induced myocardial injury in normal rat hearts, as assessed in terms of reduction in myocardial infarct size, LDH, CK and oxidative stress. However, surprisingly, IPC- and IPost-mediated myocardial protection against I/R injury was abolished in the hyperhomocysteinemic rat heart. It may be concluded that Hhcy may make the heart susceptible to oxidative stress induced by I/R, and that the high degree of oxidative stress produced in the hyperhomocysteinemic rat heart in response to reperfusion may be responsible for abolishing the cardioprotective potential of IPC and IPost against I/R injury.