Ischemic preconditioning is a well-established phenomenon first described in experimental preparations in which brief episodes of
ischemia/reperfusion applied prior to a longer coronary artery occlusion reduce
myocardial infarct size. There are ample correlates of ischemic preconditioning in the clinical realm. Preconditioning mimetic agents that stimulate the biochemical pathways of ischemic preconditioning and protect the heart without inducing
ischemia have been examined in numerous experimental studies. However, despite the effectiveness of ischemic preconditioning and preconditioning mimetics for protecting ischemic myocardium, there are no preconditioning-based
therapies that are routinely used in clinical medicine at the current time. Part of the problem is the need to administer
therapy prior to the known ischemic event. Other issues are that
percutaneous coronary intervention technology has advanced so far (with the development of
stents and
drug-eluting stents) that ischemic preconditioning or preconditioning mimetics have not been needed in most interventional cases. Recent clinical trials such as AMISTAD I and II (Acute
Myocardial Infarction STudy of
ADenosine) suggest that some preconditioning mimetics may reduce
myocardial infarct size when given along with reperfusion or, as in the IONA trial, have benefit on clinical events when administered chronically in patients with known
coronary artery disease. It is possible that some of the benefit described for
adenosine in the AMISTAD 1 and 2 trials represents a manifestation of the recently described postconditioning phenomenon. It is probable that postconditioning--in which reperfusion is interrupted with brief
coronary occlusions and reperfusion sequences--is more likely than preconditioning to be feasible as a clinical application to patients undergoing
percutaneous coronary intervention for acute
myocardial infarction.