Cellular signalling mechanisms in adaptation to ischemia-induced myocardial damage.

Ischemic heart disease is the major cause of morbidity and mortality in the Western world. Ischemia-reperfusion injury may induce cardiomyocyte cell death by necrosis or apoptosis. The heart can be adapted to tolerate an ischemic event by preceding brief episodes of ischemia and reperfusion, called preconditioning. Preconditioning protects the heart when it is directed towards the heart itself either immediately before or several days before an induced ischemic event. Adaptation by preconditioning can even be achieved in other organs, and preconditioning one organ can protect another organ. Evidence suggests that preconditioning may be a naturally occurring adaptive process in vivo, and in humans unstable angina before acute myocardial infarction may represent the phenomenon. The mechanisms underlying the response are complex and intertwined, and probably differ between acute and delayed. as well as local or remote models. Based on animal experiments, it appears that preconditioning consists of a trigger phase with release of signal substance(s), a signal transduction phase where cascade reactions are induced, and an organ effector phase where mediator(s) ensure organ protection against necrosis and apoptosis. Understanding the underlying mechanisms of action is crucial to making therapeutic use of this powerful mode of myocardial protection.