Anesthetic effects on mitochondrial ATP-sensitive K channel

Background Volatile anesthetics show an ischemic preconditioning-like cardi oprotective effect, whereas intravenous anesthetics, have cardioprotective effects for ischemic-reperfusion injury. Although recent evidence suggests that mitochondrial adenosine triphosphate-regulated potassium (mitoK(ATP)) channels are important in cardiac preconditioning, the effect of anesthetic s on mitoK(ATP) is unexplored. Therefore, the authors tested the hypothesis that anesthetics act on the mitoK(ATP), channel and mitochondrial flavopro tein oxidation. Methods: Myocardial cells were isolated from adult guinea pigs. Endogenous mitochondrial flavoprotein fluorescence, an Indicator of mitochondrial flav oprotein oxidation, was monitored with fluorescence microscopy while myocyt es were exposed individually for 15 min to isoflurane, sevoflurane, propofo l, and pentobarbital. The authors further Investigated the effect of 5-hydr oxydeanoate, a specific mitoK(ATP) channel antagonist, on isoflurane- and s evoflurane-induced flavoprotem oxidation. Additionally, the effects of prop ofol and pentobarbital on isoflurane-induced flavoprotein oxidation were me asured. Results: Isoflurane and sevoflurane induced dose-dependent increases in fla voprotein oxidation (Isoflurane: R2 = 0.71, n = 50; sevoflurane: R2 = 0.86, n = 20). The fluorescence increase produced by both isoflurane and sevoflu rane was eliminated by 5-hydroxydeanoate. Although propofol and pentobarbit al showed no significant effects on flavoprotein oxidation, they both dose- dependently inhibited isoflurane-induced flavoprotein oxidation. Conclusions: Inhalational anesthetics induce flavoprotein oxidation through opening of the mitoK(ATP) channel. This may be an important mechanism cont ributing to anesthetic-induced preconditioning. Cardioprotective effects of intravenous anesthetics may not be dependent on flavoprotein oxidation, bu t the administration of propofol or pentobarbital may potentially inhibit t he cardioprotective effect of inhalational anesthetics.