Delayed Cardioprotection by Inhaled Anesthetics

Abstract

SCHEMIC PRECONDITIONING (IPC) is a process by which a brief ischemic insult confers protection against a subsequent ischemic episode of similar or greater magnitude. Murry et al 1 first described IPC in the canine myocardium. The investigators showed that 4 transient (5 minutes) periods of coronary artery occlusion interspersed with 5 minutes of reperfusion did not enlarge as anticipated but rather paradoxically reduced the size of a myocardial infarction resulting from a subsequent more prolonged (40 minutes) episode of ischemia and reperfusion. This seminal article showed, for the first time, that the heart was capable of recognizing and rapidly adapting to stress, thereby becoming more resistant to subsequent injury. 1 Bolli et al 2-4 described this IPC phenomenon as a form of “vaccination” that stimulated the “innate plasticity” of myocardium by altering its phenotype and promoting its “self-preservation” as a primary defense mechanism. In the 25 years since IPC was first described, basic science and clinical research examining the mechanisms, limitations, and potential applicability of this process have expanded exponentially. Indeed, a recent PubMed search of the key words “myocardial ischemic preconditioning” indicated that more than 900 articles addressing this subject were published in the peer-reviewed literature in 2009 alone. 5 A large portion of this extraordinary body of work showed that a remarkable plethora of other stimuli, including a diverse variety of drugs, nitric oxide (NO), reactive oxygen species (ROS), endotoxins, inflammatory cytokines, heat stress, rapid pacing, and strenuous exercise, are capable of inducing this prosurvival phenotype, thereby protecting against irreversible ischemic injury independent of an antecedent period of brief myocardial ischemia. 6 Of most immediate relevance to this review, modern volatile anesthetics and the anesthetic noble gas xenon are among the drugs that have been shown to mimic IPC through nearly identical intracellular mechanisms. 7,8