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

Abstract

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.

In VivoDesflurane Preconditioning Evokes Dynamic Alterations of Metabolic Proteins in the Heart - Proteomic Insights Strengthen the Link between Bioenergetics and Cardioprotection

“…ROS participate in the process of APC [28,29,30,31] particularly triggering the opening of K ATP channels and preventing Ca 2+ overload in the mitochondria [2,32,33]. In accordance with that we found a down-regulation of several proteins involved in electron transport chain, including the soluble complex I subunits NDUFS1 and NDUFV1, and UQCRC1 of complex III.…”

Reverse electron flow-induced ROS production is attenuated by activation of mitochondrial Ca2+-sensitive K+ channels

“…Excess release of ROS has been shown to play a role in the etiology of various pathological disorders including cardiovascular disease (1), degenerative changes in aging (5), Alzheimer disease (29), and diabetes (22), as well as in ischemia-reperfusion (I/R) injury (42). ROS are key elements in a variety of cellular signaling pathways (24), including cardioprotection against I/R induced by ischemic and pharmacological preconditioning (27,31).…”

Is the knowledge on tissue microcirculation important for microsurgeon?

“…These oxygen species cause dilation of arterioles in the vascular bed by direct action and by activation of nitric oxide (NO). [74][75][76][77] Free oxygen radicals are formed in situ in Fenton's reaction (hydrogen peroxide þ iron sulphate). 78 Free oxygen radicals are characterized by a short half-life time and high biological activity.…”

“…They also mediate the most pathological responses of the vascular bed in stressful conditions. 77 They are released when the cell metabolic reserves become depleted. They also affect acetyl-choline-dependent vessel relaxation; therefore, the destructive effect of these compounds on the synthesis of NO is possible.…”