The therapeutic potential of ischemic conditioning: an update.

Novel approaches are required to improve clinical outcomes in patients with coronary heart disease (CHD). Ischemic conditioning--the practice of applying brief episodes of nonlethal ischemia and reperfusion to confer protection against a sustained episode of lethal ischemia and reperfusion injury--is one potential therapeutic strategy. Importantly, the protective stimulus can be applied before (ischemic preconditioning) or after (ischemic perconditioning) onset of the sustained episode of lethal ischemia, or even at the onset of myocardial reperfusion (ischemic postconditioning). Furthermore, the protective stimulus can be applied noninvasively by placing a blood-pressure cuff on an upper or lower limb to induce brief episodes of nonlethal ischemia and reperfusion (remote ischemic conditioning), a finding that has greatly facilitated the translation of ischemic conditioning to various clinical settings. In addition to mechanical approaches, elucidation of the signal-transduction pathways underlying ischemic conditioning has identified several novel targets for pharmacological conditioning. This Review highlights findings from proof-of-concept clinical studies conducted in the past 5-6 years, in which the therapeutic potential of ischemic and pharmacological conditioning has been realized. Large, randomized, controlled trials are now required to determine whether pharmacological and ischemic conditioning improve clinical end points and outcomes in patients with CHD.