The Influence Of Mitochondrial K_ATP-channels In The Cerebral Protection Of Preconditioning And Postconditoning By Sevoflurane In The Rat In Vivo

Objective In 1990 Kitagawa discovered the phenomenon of cerebral "ischemic preconditioning(IPC)." Since then ischemic postconditioning,pharmacological preconditioning and pharmacological postconditioning have been shown to mimic the most potent protective mechanism of IPC.Sevoflurane is a commonly used volatile anesthetics. Because of its low blood gas partition coefficients,induction and emergence from sevoflurane anesthesia is rapid.Sevoflurane has little influence on cardiovascular system and the incidence of arrhythmia and hypotension is low.In addition,sevoflurane in the canine model has no effect on intracranial pressure and the autonomic regulation of the central nervous system is well kept.The protective effect of sevoflurane preconditioning and postconditioning on oxygen-glucose deprivation injury in rat hippocampal slices and myocardial ischemia is generally acknowledged.Mitochondria is an important organelle that mediates cerebral ischemia-reperfusion injury,and mitochondrial ATP-sensitive-potassium channels(mitoK_ATP)have a critical role in pharmacological preconditioning,including many volatile anesthetics. We investigated the relationship between the protective effect of sevoflurane preconditioning and postconditioning against focal cerebral ischemia-reperfusion injury and the roles of mitochondrial ATP-sensitive-potassium channels(mitoK_ATP).Methods Fifty-six male SD rats weighting 250～280g were randomly allocated into seven groups(n=8).Rats were subjected to 2 hours of middle cerebral artery occlusion(MCAO)followed by 24 hours of reperfusion.The following protocols were used:1)preconditioning (S-Pre,achieved by 2.4%sevoflurane(1MAC)inhalation for 30min before MCAO);2)postconditoning(S-Post,2.4%sevoflurane given for 30min at the beginning of reperfusion).Protocols 1-2 were repeated in the presence of 5-hydroxydecanoate(5-HD),a specific mK_ATP-channel-blocker(S-Pre+5-HD,S-Post+5-HD).Eight rats served as sham operation group(Sham),untreated controls(CON)or received 5-HD alone(5-HD).Neurological deficit of the rats was assessed by Zea Longa's scoring system,infarct size was determined by TTC staining, and the expression of bcl-2 and bax in the frontal lobe of cerebral cortex was evaluated by immunohistochernistry.Results Both S-Pre and S-Post reduced infarct size and neurologic deficit compared with CON.5-HD diminished the protection in all two sevoflurane treated groups,but given alone had no effect on infarct size and neurologic deficit.Sevoflurane preconditioning and postconditioning induce the expression of bcl-2 and relatively inhibit the expression of bax.Conclusion Sevoflurane preconditioning and postconditioning protects against cerebral ischemia-reperfusion injury by regulating the expression of bcl-2 and bax protein,and is mediated,at least in part,by mitoK_ATP-channels.