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

Author:

Zhao Jianli1,Wang Feng1,Zhang Yanqing1,Jiao Liyuan1,Lau Wayne Bond1,Wang Lili1,Liu Baojiang1,Gao Erhe1,Koch Walter J.1,Ma Xin-Liang1,Wang Yajing1

Affiliation:

1. From the Department of Anesthesiology, the First Affiliated Hospital (J.Z., Y.Z., L.J., L.W., B.L.), Department of Pathophysiology (F.W.), and Department of Physiology, Key Laboratory of Cellular Physiology, Ministry of Education (Y.W.), Shanxi Medical University, Taiyuan, China; Department of Emergency Medicine, Thomas Jefferson University, Philadelphia, PA (W.B.L., X.-L.M., Y.W.); and Center for Translational Research, Temple University, Philadelphia, PA (E.G., W.J.K.).

Abstract

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 injury ( P >0.05). SF-PreCon significantly decreased MI/R-induced superoxide generation in wild-type (−43.6%) and AMPK dominant-negative overexpressing mice (−35.5%; P <0.01) but not in Cav-3 knockout mice. SF-PreCon did not affect nicotinamide adenine dinucleotide phosphate oxidase expression but significantly inhibited cyclooxygenase-2 expression in wild-type (−38.7%) and AMPK dominant-negative overexpressing mice (−35.8%) but not in Cav-3 knockout mice. Conclusions— We demonstrate for the first time SF-PreCon mediates cardioprotection against MI/R injury via caveolin-3–dependent cyclooxygenase-2 inhibition and antioxidative effects.

Publisher

Ovid Technologies (Wolters Kluwer Health)

Subject

Physiology (medical),Cardiology and Cardiovascular Medicine

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