Surgical applications of organ preconditioning

In 1986, Murry et al. reported that brief periods of antecedent ischemia in dogs paradoxically reduced (rather than exacerbated) the size of myocardial infarcts created by subsequent prolonged ischemia. This fortuitous discovery, now termed "preconditioning", stimulated further investigation of the inherent adaptive mechanisms present in a variety of tissues and organs. In addition to ischemia, it is now recognized that a protective response can be initiated by multiple means including lipopolysaccharide, heat stress, exercise, adrenergic drugs and even noise. Furthermore, preconditioning protects not only against cell death but also against postischemic contractile dysfunction, stunning and arrhythmias. Despite the preponderance of animal studies demonstrating the benefits of preconditioning, its clinical application has been hampered by clinicians' hesitancy to intentionally subject patients to a noxious stress prior to a planned intervention. However, many of the intracellular signals responsible for the protective effect of preconditioning have been delineated, and pharmacologic manipulation of these signals can accomplish the same benefits. The existence of preconditioning in humans has been demonstrated in vitro and in small clinical trials, and targeted strategies that exploit this endogenous protective mechanism promise to broaden the therapeutic potential of organ preconditioning.