Hibernation, Stunning, and Preconditioning: Historical Perspective, Current Concepts, Clinical Applications, and Future Implications

Abstract

Despite considerable advances, coronary artery disease is the leading cause of morbidity and mortality in the Western world. The development of effective therapeutic strategies for protecting the myocardium from ischemia would have major impact on patients with coronary artery disease. It is now accepted that patients with coronary artery disease can experience prolonged regional ischemic dysfunction that does not necessarily arise from irreversible tissue damage, and to some extent, can be reversed by restoration of blood flow. The initial stages of dysfunction are probably caused by chronic stunning that can be reversed after revascularization, resulting in rapid and complete functional recovery. On the other hand, the more advanced stages of dysfunction likely correspond to chronic hibernation. After revascularization, functional recovery will probably be quite delayed and mostly incomplete. Over the past decade, the possibility that an innate mechanism of myocardial protection might be inducible in the human heart has generated considerable excitement. In the last two decades, there was phenomenal growth in the understanding of the mechanism known as ischemic preconditioning that is responsible for the innate myocardial protection. Continued research and progress in this area may soon lead to the availability of preconditioning-mimetic treatments. The current concepts, mechanisms, and potential clinical applications of myocardial hibernation, stunning, and ischemic preconditioning are reviewed. M yocardial infarction continues to be among the most frequent causes of debilitating illness and death. Tissue damage from myocardial infarction occurs as a result of the initial ischemic event, primarily determined by its duration, and the subsequent injury resulting from reperfusion.In the past 15 years, understanding of the pathophysiologic processes involved in chronic and From the