Preconditioning: Can nature's shield be raised against surgical ischemic-reperfusion injury?

Endogenous myocardial protection refers to the natural defense mechanisms a vailable to the heart to withstand an ischemic injury. So far, these mechan isms have been shown to encompass two phenomena most likely interrelated: i schemic preconditioning and stress protein synthesis. Ischemic precondition ing can be defined as the adaptive mechanism induced by a brief period of r eversible ischemia increasing the heart's resistance to a subsequent longer period of ischemia. The therapeutic exploitation of these natural adaptive mechanisms in cardiac surgery is an appealing prospect, as preconditioning could be used before aortic cross-clamping to enhance the current methods of myocardial protection. Two major conclusions emerge from the bulk of exp erimental data on preconditioning: First, the adaptive phenomenon reduces i nfarct size after regional ischemia in animal preparations across a wide va riety of species but its effects on arrhythmias and on preservation of func tion after global ischemia are less consistent. This is relevant to cardiac surgery where postbypass pump failure is more often due to stunning than t o discrete necrosis. Second, regardless of the various components of the in tracellular signaling pathway elicited by the preconditioning stimulus, it seems that the major mechanisms by which this pathway leads to a cardioprot ective effect are a slowing of adenosine triphosphate depletion and a limit ation of acidosis during the protracted period of ischemia. If the latter i s true, then it can reasonably be predicted that these energy-sparing and a cidosis-limiting effects may become redundant to those of cardioplegia. Fro m these observations, it can be inferred that preconditioning may find an e lective indication in situations where the potential for suboptimal protect ion increases the risk of necrosis (extensive coronary artery disease, seve re left ventricular hypertrophy, long ischemic time, and beating heart oper ations where occlusion of the target vessels leads to unprotected distal is chemia). Since an ischemic preconditioning stimulus could be clinically und esirable, it is critically important to identify the endogenous mediators o f the phenomenon in order to use them therapeutically. One of the most impo rtant of these mediators seems to be the adenosine triphosphate-dependent p otassium channel. Currently, however, the clinical application of these dru gs is hampered by their poor cardioselectivity which could result in untowa rd systemic vasodilatory effects before cardioprotection becomes manifest. Thus, although the modalities of pharmacologically induced preconditioning still remain to be determined, the concept of therapeutic exploitation of t he endogenous adaptive mechanisms of the heart could potentially represent an important adjunct to our current techniques of myocardial protection. (C ) 1999 by The Society of Thoracic Surgeons.