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CARDIOVASCULAR ANESTHESIOLOGY

Myocardial Protection by Isoflurane Preconditioning Preserves Ca²⁺ Cycling Proteins Independent of Sarcolemmal and Mitochondrial K_ATP Channels

Jianzhong An, MD^*, Zeljko J. Bosnjak, PhD^*, and Ming Tao Jiang, MB, PhD^*

From the Departments of *Anesthesiology and Physiology, Medical College of Wisconsin, Milwaukee, Wisconsin.

Address correspondence and reprint requests to Jianzhong An, MD, Department of Anesthesiology, Medical College of Wisconsin, 8701 Watertown Plank Rd., Milwaukee, WI 53226. Address e-mail to jzan{at}mcw.edu.

Abstract

INTRODUCTION: Anesthetic preconditioning (APC) with volatile anesthetics improves recovery of contractile function and reduces calcium overload after ischemia/reperfusion (I/R). Mitochondrial and sarcolemmal K_ATP channel openings have been implicated in APC-induced cardioprotection. In this study, we investigated the effect of APC on major calcium cycling proteins and its relation to K_ATP channels.

METHODS: Isolated perfused rat hearts were divided into seven groups: Time control (n = 10), ischemia control (n = 8), APC (n = 8), Mitochondrial K_ATP inhibitor 5-hydroxydecanoate (5-HD, 200 µM, n = 8), Sarcolemmal K_ATP inhibitor HMR1098 (HMR, 20 µM, n = 8), and APC plus 5-HD or APC plus HMR1098 (n = 8 each). APC was initiated by administering 1.5% isoflurane for 15 min, followed by a 15 min washout before 30 min of myocardial ischemia and 60 min of reperfusion. Ca²⁺-release channels (RyR2), Ca²⁺-adenosine triphosphatase (SERCA2a), phospholamban, plasma membrane Ca²⁺ ATPase, and sodium–calcium exchanger in the homogenate were determined by Western blot assay.

RESULTS: APC improved contractile recovery (left ventricular developed pressure, +dP/dt, –dP/dt) after I/R, which was blocked by 5-HD and HMR. I/R depressed the density of RyR2, SERCA2a, and phospholamban, with no changes in the density of plasma membrane Ca²⁺ ATPase and sodium–calcium exchanger. APC reversed I/R-induced degradation of RyR2 and SERCA2a in the presence or absence of 5HD and HMR.

CONCLUSIONS: I/R-induced depression in cardiac performance is associated with a down-regulation of the major sarcoplasmic reticulum Ca²⁺-cycling proteins. Anesthesia preconditioning with isoflurane prevents I/R-related degradation of the RyR2 and SERCA2a in the sarcoplasmic reticulum. However, this effect was independent of its activation of K_ATP channels.

Anesthesia & Analgesia® is published for the International Anesthesia Research Society® by Lippincott Williams & Wilkins with the assistance of Stanford University Libraries' HighWire Press®. Copyright 2006 by the International Anesthesia Research Society. Online ISSN: 1526-7598   Print ISSN: 0003-2999