The relationship between ischemia-reperfusion injury, myocardial stunning and cardiac preconditioning.

The high incidence of coronary disease in the current population renders myocardial ischemia a leading cause of morbidity and death. Recent efforts have made rapid restoration of coronary flow a clinical reality. Despite progress in hypothermic arrest and cardioplegia, the widespread performance of open cardiac operation and increasing use of cardiac transplantation obligate myocardial I/R stress. Advances in understanding the pathophysiologic factors of reversible and irreversible I/R injury have been significant, but are incomplete. Myocardial infarction and myocardial "stunning" remain clinically important sequelae of coronary disease. In the long term, the solution to heart disease will likely come through preventative health measures. In the interim, however, measures to limit ischemic duration and prepare the heart for reperfusion are clinically desirable. The presence of intrinsic cellular protective mechanisms intimate the feasibility of the latter measure. Furthermore, recently delineated receptor-mediated mechanisms of ischemic preconditioning may render this phenomenon clinically exploitable. The multifactorial pathophysiologic nature of the I/R process suggests that optimal intervention will likely require a combination of pharmacologic adjuncts intended for the specific type and severity of I/R insult. Continued exploration of I/R pathophysiologic factors is needed to develop practical therapeutic interventions.