Sevoflurane protects stunned myocardium through activation of mitochondrial ATP-sensitive potassium channels

We sought to determine the hemodynamic and cardioprotective effects of sevo flurane in canine stunned myocardium. Forty-nine dogs were allocated to one of seven groups (n = 7 for each). In six separate groups, dogs received ve hicle, glibenclamide (a nonselective adenosine triphosphate-dependent potas sium [K-ATP] channel antagonist) (0.3 mg/kg IV) or 5-hydroxydecanoic acid ( a mitochondrial K-ATP channel antagonist) (5 mg/kg IV) in the presence or a bsence of 1 minimum alveolar concentration (1 MAC) sevoflurane. In an addit ional group, dogs received 1 MAC sevoflurane with hemodynamic correction. R egional myocardial contractility was evaluated with segment shortening. Mea surements were made before and during 15-min ischemia and 90-min reperfusio n. Recovery of segment shortening 90 min after reperfusion was significantl y improved in the dogs anesthetized with sevoflurane either with or without hemodynamic correction (70.1 +/- 4.2 and 75.9 +/- 3.1% of baseline, respec tively), whereas the recovery was poor in control and glibenclamide or 5-hy droxydecanoic acid pretreated dogs (33.3 +/- 4.3, 33.8 +/- 6.8, and 45.0 +/ - 5.5% of baseline, respectively). Regional myocardial perfusion showed no significant difference among groups. The results indicate that sevoflurane has a cardioprotective effect mediated through activation of mitochondrial K-ATP channels and independent of coronary blood flow or reduction in cardi ac work.