Cardioprotection Against Ischemia-Reperfusion Injury By Na～+/Ca～(2+) Exchange Inhibitor And Antioxidant In The Very Early Moments Of Reperfusion

Ischemia preconditioning was the most potent endogenous form cardioprotection against ischemia-reperfusion injury. In clinic practice, however, this pretreatment manipulation was limited because the onset of myocardial ischemia was unexpected. In 2003, Zhao et al. reported another endogenous form of cardioprotection that exerted cardioprotection similar to that observed with preconditioning. In this study, a short series of repetitive cycles of brief reperfusion and re-occlusion of coronary artery applied immediately at the moments of reperfusion, termed postconditioning. Interestingly, previous study by Zhao et al. reported that the negative results were occurred when the postconditioning manipulation operated by three 5-min on-off cycles over the first 30 min of reperfusion rather than by three 30-sec on-off cycles over the first 3 min of reperfusion as they did recently. The results from that study suggested that the time windows on which the mechanical manipulation was given to produce the postconditioning cardioprotection was in the very early moments of reperfusion (being first 3 minutes of reperfusion in canine).Late, the cardioprotection against ischemia-reperfusion injury by postconditioning was confirmed in rabbit heart. In that time, however, mentioned cardioprotection in rat heart have not been reported. In present study, we will observe the cardioprotection against ischemia-reperfusion injury by postconditioning in rat heart and determine the optimal time window for mechanical manipulation in rat heart. The results from our experiment indicated that the postconditioning cardioprotection in rat heart was functional and the time window on which the mechanical manipulation was optimal for offering a cardioprotection against ischemia-reperfusion injury was the first minute of reperfusion in rat.On the base of our previous study, we try to test the hypothesis that the same effects of cardioprotection could be obtained by drug intervention instead of mechanical manipulation in the same time window of early reperfusion phase, which might be of important value in clinic practice. In line with many previous studies, the generation of reactive oxygen species (ROS) and intracellular Ca2+ overload play crucial roles in initiating downstream pathophysiologic consequences of ischemia-reperfusion injury. Accordingly, reduced glutathione (GSH), a antioxidant, and KB-R7943, a Na+-Ca2+ exchange inhibitor, were applied during the very early moment of reperfusion in cardiac ischemia-reperfusion mode in situ to examine the protective effects of them and compare those of mechanical process on ischemia-reperfusion heart. To...