Effects of diabetes on myocardial infarct size and cardioprotection by preconditioning and postconditioning

Cardiovascular diseases are the leading cause of death, accounting for approximately 30% of all deaths worldwide [1]. Among the various cardiovascular diseases, acute myocardial infarction (AMI) has a high rate of mortality, and infarct size is a primary determinant of prognosis in these patients. The only established and clinically approved method to limit infarct size is restoration of coronary blood flow by percutaneous coronary interventions (PCI), thrombolytic agents or coronary bypass surgery. However, our recent review of clinical infarct size data indicated that infarct size after current reperfusion therapy was larger than 75% of the area at risk and larger than 20% of the left ventricle in one fourth of AMI patients [2]. Lack of substantial myocardial salvage in those patients cannot be simply attributable to long symptom-to-reperfusion time, and involvement of reperfusion injury [3] is also possible. Nevertheless, significant percentages of AMI patients suffer from insufficient cardiac function and have a poor prognosis even after successful restoration of coronary flow [2]. Therefore, the establishment of a novel strategy to limit the extent of infarction during ischemia/reperfusion is of great clinical importance.As a cardioprotective strategy, ischemic preconditioning (PC) has received much attention for its potent infarct size-limiting effect since its first report by Murry et al. in 1986 [4]. Zhao et al. found that “conditioning” with repetitive ischemia/reperfusion at the time of reperfusion also affords protection and named the phenomenon ischemic postconditioning (PostC) [5]. Laboratory investigations to date have clarified outlines of the intracellular mechanisms of PC and PostC [6-9]. In addition, several agents targeting signaling relevant to PC and PostC have been shown to act as PostC mimetics [6-8]. However, clinical benefits of PC, PostC and their mimetics were not always demonstrated in clinical trials [8,10]. The discrepancy between resul