Anesthetic Preconditioning: The Role of Free Radicals in Sevoflurane-Induced Attenuation of Mitochondrial Electron Transport in Guinea Pig Isolated Hearts

Abstract
Xposure as part of the triggering mechanism of APC. We hypothesized that NO· and other ROS mediate anesthetic-induced ET attenuation. Cardiac function and reduced nicotinamide adenine dinucleotide (NADH) fluorescence, an index of mitochondrial ET, were measured online in 68 Langendorff-prepared guinea pig hearts. Hearts underwent 30 min of global ischemia and 120 min of reperfusion. Before ischemia, hearts were temporarily perfused with superoxide dismutase, catalase, and glutathione to scavenge ROS or NG-nitro-l-arginine-methyl-ester (l-NAME) to inhibit NO· synthase in the presence or absence of 1.3 mM sevoflurane (APC). APC temporarily increased NADH before ischemia, i.e., it attenuated mitochondrial ET. Both this NADH increase and the cardioprotection by APC on reperfusion were prevented by superoxide dismutase, catalase, and glutathione and by NG-nitro-l-arginine-methyl-ester. Thus, ROS and NO·, or reaction products including peroxynitrite, mediate sevoflurane-induced ET attenuation. This may lead to a positive feedback mechanism with augmented ROS generation to trigger APC secondary to altered mitochondrial function....

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