TITLE

Contractile recovery of heart muscle after hypothermic hypoxia is improved by nicorandil via mitochondrial KATP channels

AUTHOR(S)
Steensrud, Tor; Jakobsen, Øyvind; Ytrehus, Kirsti; Sørlie, Dag G.
PUB. DATE
August 2006
SOURCE
European Journal of Cardio-Thoracic Surgery;Aug2006, Vol. 30 Issue 2, p256
SOURCE TYPE
Academic Journal
DOC. TYPE
Article
ABSTRACT
Abstract: Background: The ATP-sensitive potassium channel (KATP) opener nicorandil used instead of potassium in hypothermic cardioplegia significantly improves preservation of cardiac function and energetics in the in situ heart preparation. The present study, therefore, examines the effect of nicorandil at different temperatures and the role of sarcolemmal and mitochondrial KATP channels under ex vivo conditions using contractile force (CF) and action potential duration (APD) as end points. Methods: Guinea-pig papillary muscles at 37, 27, or 22°C (1Hz) were exposed to nicorandil 0.2–1.1mM. The contributions of KATP channel subtypes in cardioprotection were examined using mitochondrial (mito) (0.1mM) or non-selective (1.0mM) concentrations of nicorandil, mito KATP blocker 5-hydroxyl decanoate (5HD, 300μM) or sarcolemmal (sarc) KATP blocker HMR1098 (30μM) before and during 140min of hypothermic (22°C) glucose-free hypoxia. Results: Nicorandil >0.5mM shortened the APD, and this was abolished by hypothermia and HMR1098 but not by 5HD. Nicorandil in both tested concentrations preserved contractile force after hypoxia–reoxygenation significantly better than control (73.7±4.4% and 75.8±3.9% vs 40.6±2.6%, n =6 in each group). Protection was blocked by 5HD but not by HMR1098. 5HD and HMR1098 alone did not change recovery of contractile force compared to control. Conclusion: Shortening of APD and activation of sarc KATP by nicorandil were not related to myocardial protection. Thus, the mito KATP seems to play a significant role in cardioprotection compared to the sarc KATP also when substrate depletion and hypoxia are combined with hypothermia.
ACCESSION #
21665221

 

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