Ischemic preconditioning: From molecular mechanisms to therapeutic opportunities

Ischemia/reperfusion (I/R) injury is a major contributory factor to cardiac dysfunction and infarct size that determines patient prognosis after acute myocardial infarction. Considerable interest exists in harnessing the heart's endogenous capacity to resist I/R injury, known as ischemic preconditioning (IPC). The IPC research has contributed to uncovering the pathophysiology of I/R injury on a molecular and cellular basis and to invent potential therapeutic means to combat such damage. However, the translation of basic research findings learned from IPC into clinical practice has often been inadequate because the majority of basic research findings have stemmed from young and healthy animals. Few if any successful implementations of IPC have occurred in the diseased hearts that are the primary target of viable therapies activating cardioprotective mechanisms to limit cardiac dysfunction and infarct size. Therefore, the first purpose of this review is to facilitate understanding of pathophysiology of I/R injury and the mechanisms of cardioprotection afforded by IPC in the normal heart. Then I focus on the problems and opportunities for successful bench-to-bedside translation of IPC in the diseased hearts.