Sevoflurane Preconditioning Attenuates Myocardial Ischemia/Reperfusion Injury via Caveolin-3–Dependent Cyclooxygenase-2 Inhibition

Background—The inhaled anesthetic sevoflurane has been demonstrated to protect against myocardial ischemia/reperfusion (MI/R) injury via mechanisms involving AMP-activated protein kinase (AMPK) and caveolin-3 (Cav-3). However, the relative contributions of AMPK and Cav-3 to sevoflurane preconditioning (SF-PreCon)–mediated cardioprotection and their precise underlying mechanisms of action remain incompletely understood. Methods and Results—SF-PreCon (consisting of 3 cycles of 15-minute exposure to 2% sevoflurane before 30 minutes of MI) decreased MI/R injury in wild-type mice (caspase-3 activity, −29.1%; infarct size, −20.2%; and left ventricular end diastolic pressure, −33.8%). In cardiac-specific AMPKα2 dominant-negative overexpressing mice, the cardioprotective effect of SF-PreCon was largely retained (caspase-3 activity, −26.7%; infarct size, −16.7%; and left ventricular end-diastolic pressure, −25.9%; P<0.01). In contrast, SF-PreCon failed to significantly protect Cav-3 knockout mice against MI/R inju...