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CARDIOVASCULAR ANESTHESIA

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

Matthias L. Riess, MD, PhD^*,,, Leo G. Kevin, FCARCSI^*, Joseph McCormick, BS, Ming T. Jiang, PhD^*, Samhita S. Rhodes, PhD^*, and David F. Stowe, MD, PhD^*,,||,¶,#

*Anesthesiology Research Laboratories, Departments of Anesthesiology and Physiology and ||Cardiovascular Research Center, Medical College of Wisconsin, Milwaukee, Wisconsin; Westfälische-Wilhelms-Universität, Münster, Germany; and ¶Veterans Affairs Medical Center Research Service and #Department of Biomedical Engineering, Marquette University, Milwaukee, Wisconsin

Address correspondence and reprint requests to David F. Stowe, MD, PhD, Medical College of Wisconsin, 8701 Watertown Plank Rd., Milwaukee, WI 53226. Address e-mail to dfstowe{at}mcw.edu

Cardioprotection by anesthetic preconditioning (APC) can be abolished by nitric oxide (NO^·) synthase inhibitors or by reactive oxygen species (ROS) scavengers. We previously reported attenuated mitochondrial electron transport (ET) and increased ROS generation during preconditioning sevoflurane exposure 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 N^G-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 N^G-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.

IMPLICATIONS: Nitric oxide and other reactive oxygen species mediate sevoflurane-induced attenuation of mitochondrial electron transport in Langendorff-prepared hearts. This may lead to a positive feedback mechanism that initiates cardiac anesthetic preconditioning and attenuates ischemia/reperfusion injury.

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