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CARDIOVASCULAR ANESTHESIA

Activation of Protein Kinase C Contributes to the Isoflurane-Induced Improvement of Functional and Metabolic Recovery in Isolated Ischemic Rat Hearts

Pengcheng Xu, MD^*,, Jun Wang, MD^*,, Ramesh Kodavatiganti, MD^*, Yinming Zeng, MD, and Ira S. Kass, PhD^*,,

Departments of *Anesthesiology and Physiology & Pharmacology, State University of New York Downstate Medical Center, Brooklyn, New York; and Anesthesiology Key Laboratory of Jiangsu Province, Xuzhou Medical College, Xuzhou, People’s Republic of China

Address correspondence and reprint requests to Jun Wang, MD, Department of Anesthesiology, Box 6, SUNY Downstate Medical Center, 450 Clarkson Ave., Brooklyn, NY 11203. Address e-mail to jwang{at}downstate.edu

Isoflurane enhances myocardial functional recovery and improves energy levels after ischemia. We sought to determine whether isoflurane-induced cardioprotection is mediated by protein kinase C (PKC). The Langendorff model was used, and isolated perfused rat hearts were separated into untreated, isoflurane, chelerythrine (PKC inhibitor) plus isoflurane, and chelerythrine groups. All hearts were subjected to treatment before ischemia, followed by 30 min of ischemia and 60 min of reperfusion. We recorded hemodynamic variables, measured metabolites by high-performance liquid chromatography, and analyzed subcellular localization of PKC isoforms by Western blot analysis. Isoflurane significantly improved the recovery of left ventricular developed pressure, attenuated the depletion of myocardial adenosine triphosphate (ATP) and creatine phosphate at 15 min of ischemia, enhanced the recovery of myocardial ATP and creatine phosphate concentrations after ischemia, and was associated with the translocation of PKC- and - to the membrane. Chelerythrine suppressed the translocation of PKC- and - and blocked the improvement of cardiac function and ATP. We conclude that isoflurane delays the decrease in ATP during ischemia and improves the recovery of mechanical function and the energy state 60 min after ischemia. These effects of isoflurane are dependent on the activation of PKC.

IMPLICATIONS: Protein kinase C activation is part of the mechanism by which isoflurane improves functional and metabolic recovery after ischemia in isolated rat hearts.

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