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

Abstract

We sought to determine the hemodynamic and cardioprotective effects of sevoflurane in canine stunned myocardium. Forty-nine dogs were allocated to one of seven groups (n = 7 for each). In six separate groups, dogs received vehicle, glibenclamide (a nonselective adenosine triphosphate-dependent potassium [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 absence of 1 minimum alveolar concentration (1 MAC) sevoflurane. In an additional group, dogs received 1 MAC sevoflurane with hemodynamic correction. Regional myocardial contractility was evaluated with segment shortening. Measurements were made before and during 15-min ischemia and 90-min reperfusion. Recovery of segment shortening 90 min after reperfusion was significantly improved in the dogs anesthetized with sevoflurane either with or without hemodynamic correction (70.1 +/- 4.2 and 75.9 +/- 3.1% of baseline, respectively), whereas the recovery was poor in control and glibenclamide or 5-hydroxydecanoic 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 cardiac work. Sevoflurane exerts a cardioprotective effect that is mediated via activation of adenosine triphosphate-sensitive potassium channels in ischemic canine hearts.