Cardioprotection Of Sevoflurane Preconditioning Against Ischemia-reperfusion Injury In Rat In Vivo And Its Mechanism

Objective: Sevoflurane preconditioning protects the heart from ischemia-reperfusion injury. Many studies have shown the action of reactive oxygen species. As ROS was considered to be the origin of ischemia reperfusion injury, sevoflurane preconditioning greatly attenuated the generation of ROS during ischemia reperfusion injury. There are also experiments that show that sevoflurane preconditioning generates ROS. It remains to be elucidated how this happened. This study investigated in what way the reactive oxygen species decrease the generation of itself and the role of nitric oxide, superoxide dismutase, glutathione peroxide and catalase.Methods:60 rats, allocated into eight groups randomly, were studied. Following 2% sevoflurane preconditioning for 30min, the left anterior descending artery was ligated for 30min and then reperfused for 120 min in vivo. Cardioprotection was demonstrated by infarction size measured with 2,3,5-triphenyltetrazoliumchloride and myocardial apoptotic index measured with TUNEL. The reactive oxygen species fluorescent probe Dihydroethidium was used for the measurement of reactive oxygen species; reactive oxygen species scavenger N-(2-Mercaptopropionyl) glycine and nitric oxide synthase inhibitor Nco-nitro-L-arginine methyl ester were employed to block their action; The myocardium was homogenized for the measurement of nitric oxide, superoxide dismutase, glutathione peroxide and catalase with microplate reader. The data were expressed as mean±standard deviation (x±s), homogeneity of variance tests were performed with Levene's test; Differences between groups were compared with one-way analysis of variance and post hoc test multiple comparison with Turkey. When two-tailed P value was<0.05 were considered statistically different. Results:Sevoflurane preconditioning mediated production of reactive oxygen species before ischemia-reperfusion injury (12.0±0.8vs2.6±0.5, P<0.05) and it is lower after ischemia-reperfusion injury (16.2±0.9vs24.9±1.3, P<0.05) compare with untreated group. N-(2-Mercaptopropionyl) glycine decrease the elevation of reactive oxygen species before ischemia-reperfusion injury (5.1±0.7vsl2.0±0.8, P<0.05) and it is as high as untreated group after ischemia-reperfusion injury (24.9±1.4vs24.9±1.3, P=1.0). Sevoflurane preconditioning also mediated generation of nitric oxide (34.5±3.2vsl5.9±1.4, P<0.05), superoxide dismutase (1.5±0.5vs0.6±0.2, P<0.05), glutathione peroxide (22.8±2.5vsl2.7±2.2, P<0.05) and catalase (15.5±1.8vsl1.2±1.4, P<0.05) compare with untreated group; N-(2-Mercaptopropionyl) glycine blocked the increase of nitric oxide (P=0.993), superoxide dismutase (P=0.52), glutathione peroxide (P=0.282) and catalase (P=0.282) and the protection of sevoflurane preconditioning. Nω-nitro-L-arginine methyl ester attenuated the increase of superoxide dismutase, glutathione peroxide and catalase and the protection of sevoflurane preconditioningConclusion:Sevoflurane preconditions 30 min protects the heart of a rat from ischemia-reperfusion injury in vivo by reducing its infarction size and apoptosis; Sub-lethal amounts of reactive oxygen species generated by sevoflurane preconditioning induce superoxide dismutase, glutathione peroxide, catalase and nitric oxide and results in inhibition of the formation of reactive oxygen species at ischemia-reperfusion injury.