Effects Of Sevoflurane Preconditioning On Myocardial Expression Of GSK3β And STAT5A In Patients Undergoing Valve Replacement

Objective: Heart surgery is an important therapy method for heart diseases.Myocardial ischemia/reperfusion(I/R)injury has become an important problem of it,which increases the incidence of adverse events and mortality in patients.Inflammatory response is a serious complication caused by cardiopulmonary bypass and operation stimulation,which include the activation of numerous inflammatory cells and the release of cytokines,and eventually leads to organs injury.The cardioprotective and anti-inflammatory effects of inhalation anesthetic-induced preconditioning(APC)have been demonstrated by a number of basic experiments while only few clinical researches with controversial results.The mechanisms underlying APC are mumerous and complex,thus without a clear answer.Current paradigm suggests that APC mediates its cardiprotective effects by initiating the endogenous protective signaling pathways like its ischemic preconditioning(IPC)counterparts.The glycogen synthase kinase 3β(GSK3β)and signal transducer and activator of transcription(STAT)are the crucial downstream targets of the endogenous protective signaling pathways,which play an important role in anti-ischemic reperfusion injury.At present,few studies concentrate on the changes of GSK3β before ischemia when APC completed.And STAT3 is considered to have anti-ischemic effects while whether STAT5 A possesses these functions is unknown.This experiment aims to explore the effects of sevofluane preconditioning on myocardial injury and inflammatory response by comparing plasma concentrations of TNFα,IL-6 and c TnI as well as activity of CK-MB between sevofluane preconditioning group and total intravenous anaesthesia group.In addition,determine the expression of GSK3β,STAT5 A and their phosphorylated counterparts.Thus,exploring possible mechanisms and providing clinical evidence for APC.Methods: twenty-four patients scheduled for valve replacemen were randomly divided into 2 groups: sevoflurane preconditioning group(n=12)and total intravenous anesthesia control group(n=12).2%-5% sevoflurane and 4L/min oxygen flow were administered after intubation,and they were adjusted according to end-tidal sevoflurane concentration(CETSevo)to maintain it 1MAC for twenty min followed by a 10 min washout before CPB to maintain CETSevo less than 0.1MAC in sevoflurane preconditioning group,the intravenous anesthesia control group did not.keep hemodynamic stable with vasoactive drugs to during the process.Recorded the CPB time,operation time,aortic cross lamping time,dobutamine use and postoperative incidence of adverse events;recorded the mean blood pressure(MAP)and heart rate(HR)before anesthesia,the time just before and after CPB and 2h as well as 24 h after aorta declamping repectively.Blood samples were collected for detection of plasma concentration of TNFa,IL-6 by ELISA,c TnⅠby bidirectional lateral flow immunoassay and creatine-MB activity by immumosuppressiom assay after anesthesia induction(T0),at 2h(T1),6(T2),24(T3)and 48(T4)after aorta declamping respectively.A biopsy of the atrium was taken between the end of washout period and start of the CPB to determine the expression of expression of GSK3β,STAT5 A and their phosphorylated counterparts by western blot.Results: There were no significant difference between the two groups in preoperative general information and operation time.After operation,one patient in sevoflurane preconditioning group suffered from cardiac arrest and was improved by cardiopulmonary resuscitation while no adverse events occurred in the control group.there was no significant difference between the two groups(P>0.05);There was no difference in dobutamine use at 24 h after aortic declamping in two groups(P>0.05).There was no significant difference in MAP and HR between the two groups at each time point.(P>0.05).The differences were not statistically significant at T0(P>0.05).Compared with T0,the concentrations of c Tn I,TNFα,IL-6 and the activity CK-MB at T1-T3 were increased in both groups.Compared with the control group,the concentration of TNF α at T1-T2 and IL-6 at T1-T3 in the sevoflurane preconditioning group were decreased(P<0.05),while the concentrations of c TnⅠ and the activity of CK-MB were found no differences(P>0.05).compared with control group,The expression of phosphorylated GSK3β and STAT5 A in sevoflurane preconditioning groups were significantly increased(0.9369±0.1122 vs 0.4551±0.2717,P=0.0469;1.3349±0.3289 vs 0.8281±0.2279,P=0.0058).Conclusion:(1)Although sevoflurane preconditioning failed to decrease the plasma c TnI concentration in patients undergoing cardiac valve replacement surgery,it decrease plasma TNFα IL-6 concentration.Thus,it has a certain protective effects.(2)The mechanisms underlying sevoflurane induced protective effects may involve the enhanced phosphorylation of GSK3β and STAT5 A in patients undergoing cardiac valve replacement surgery.