New insights into potential mechanisms of ischemic preconditioning.

O ur concepts of myocardial injury have undergone considerable revision in recent years. Traditionally, myocardium reversibly injured by an episode of ischemia was thought to be more vulnerable to the effects of a subsequent episode; an extension of this view was that brief repeated ischemic episodes might cumulatively cause infarction. Multiple studies have now shown that this is not the case. Paradoxically, brief episodes of ischemia increase the heart's tolerance to a subsequent sustained period of ischemia, such that the rate of cell death is slowed substantially. Induction of tolerance in this manner has been termed ischemic preconditioning.1 In the current issue of Circulation, Liu et a12 have provided new evidence for a role for adenosine in mediating this ischemic tolerance. In this editorial comment we shall review what is known about the basic biology of preconditioning and its potential mechanisms, including the adenosine hypothesis, and address what is unknown and in need of future study.

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