Faculty Collaboration Database

Myocardial protection by isoflurane preconditioning preserves Ca2+ cycling proteins independent of sarcolemmal and mitochondrial KATP channels. Anesth Analg 2007 Nov;105(5):1207-13, table of contents

Date

10/26/2007

Pubmed ID

17959942

DOI

10.1213/01.ane.0000281053.13929.d0

Scopus ID

2-s2.0-37349117286 (requires institutional sign-in at Scopus site)   23 Citations

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 microM, n = 8), Sarcolemmal K(ATP) inhibitor HMR1098 (HMR, 20 microM, 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.

Author List

An J, Bosnjak ZJ, Jiang MT

MESH terms used to index this publication - Major topics in bold

Animals
Calcium
In Vitro Techniques
Ischemic Preconditioning, Myocardial
Isoflurane
Male
Mitochondria, Heart
Myocardial Infarction
Potassium Channels
Rats
Rats, Wistar
Ryanodine Receptor Calcium Release Channel
Sarcolemma