Sarcolemmal and mitochondrial adenosine triphosphate-dependent potassium channels - Mechanism of desflurane-induced cardioprotection

Background Volatile anesthetic-induced preconditioning is mediated by adenosine triphosphate-dependent potassium (K-ATP) channels; however, the subcellular location of these channels is unknown. The authors tested the hypothesis that desflurane reduces experimental myocardial infarct size by activation of specific sarcolemmal and mitochondrial K-ATP channels. Methods: Barbiturate-anesthetized dogs (n = 88) were acutely instrumented for measurement of aortic and left ventricular pressures. All dogs were subjected to a 60-min left anterior descending coronary artery occlusion followed by 3-h reperfusion. In four separate groups, dogs received vehicle (0.9% saline) or the nonselective K-ATP channel antagonist glyburide (0.1 mg/kg intravenously) in the presence or absence of 1 minimum alveolar concentration desflurane. In four additional groups, dogs received 45-min intracoronary infusions of the selective sarcolemmal (HMR 1098; 1 mu g . kg(-1) . min(-1)) or mitochondrial (5-hydroxydecanoate [5-HD]; 150 mu g . kg(-1) . min(-1)) K-ATP channel antagonists in the presence or absence of desflurane. Myocardial perfusion and infarct size were measured with radioactive microspheres and triphenyltetrazolium staining, respectively. Results: Desflurane significantly (P < 0.05) decreased infarct size to 10 +/- 2% (mean +/- SEM) of the area at risk as compared with control experiments (25 +/- 3% of area at risk). This beneficial effect of desflurane was abolished by glyburide (25 +/- 2%) of area at risk. Glyburide (24 +/- 12%), HMR 1098 (21 +/- 4%), and 5-HD (24 +/- 2% of area at risk) alone had no effects on myocardial infarct size. HMR 1098 and 5-HD abolished the protective effects of desflurane (19 +/- 3% and 22 +/- 2% of area at risk, respectively). Conclusion Desflurane reduces myocardial infarct size in vivo, and the results further suggest that both sarcolemmal and mitochondrial K-ATP channels could be involved.