Cardiac preconditioning by volatile anesthetic agents: a defining role for altered mitochondrial bioenergetics

Abstract

Volatile anesthetic agents, such as halothane, isoflurane, and sevoflurane, are the drugs most commonly used to maintain the state of general anesthesia. They have long been known to provide some protection against the effects of cardiac ischemia and reperfusion. Several mechanisms likely contribute to this cardioprotection, including coronary vasodilation, reduced contractility with corresponding decreased metabolic demand, and a direct effect to decrease myocardial Ca(2+) entry through L-type Ca(2+) channels. Recently, a memory phase to cardioprotection has been observed by these agents, which is inhibited by ATP-sensitive potassium channel inhibition. These features suggest a pathway that shares components with those required for ischemic preconditioning, despite the remarkable differences between these two stimuli, and the term anesthetic preconditioning (APC) has been adopted. Scavengers of reactive oxygen species (ROS) abrogate APC, suggesting an effect of anesthetic agents to cause ROS formation. Such an effect has recently been directly demonstrated. The mechanism by which these drugs induce ROS formation is unclear. However, direct inhibition of mitochondrial electron transport system enzymes, and altered mitochondrial bioeneregtics in hearts preconditioned by volatile anesthetics, strongly implicate the mitochondria as the target for these effects. Furthermore, decreased mitochondrial ROS formation during ischemia and reperfusion in hearts preconditioned by volatile anesthetics might underlie the improved postischemic structure and function. APC presents a safe mode to apply preconditioning to human hearts. This review summarizes the major developments in a field that is exciting to clinicians and basic scientists alike.