Ischemic preconditioning: exploring the paradox

Brief transient episodes of nonlethal myocardial ischemia protect or "precondition" the heart and render the myocardium resistant to a subsequent more sustained ischemic insult. The hallmark of this phenomenon--documented in virtually all species and experimental models evaluated to date in countless laboratories worldwide--is the profound reduction in infarct size seen in preconditioned groups versus time-matched controls. Efforts to identify the cellular mechanisms responsible for this paradoxical ischemia-induced cardioprotection, to expand the definition of ischemic preconditioning beyond infarct size reduction, and, perhaps most importantly, to evaluate the efficacy of preconditioning in disease models and in the clinical setting, are all topics of intensive ongoing investigation.