| PrefaceThe postconditioning of volatile anesthetics has a protective effect on isolated rat hearts suffered from ischemic/reperfusion injury.It can reduce the infarction size and improve the recovery of cardiac function significantly.This article was scheduled to observe protective effects and mechanisms of sevoflurane postprocessing in myocardial ischemia/reperfusion in isolated rat hearts.Mitochondrial permeability transition is thought to be a major cause of reperfusion injury,and is probably responsible for damaging heart during ischemia reperfusion.Mitochondrial permeability transition pore(MPTP)opens during reperfusion,and that the extent of functional recovery of a heart is inversely correlated with pore opening.The immunosuppressant cyclosporine A,which inhibits the MPTP in isolated mitochondria,protects isolated rat hearts and cardiac myocytes against ischemia-reperfusion damage5-7.Most recently,inhibition of MPTP was shown to mediate the protective effects of repetitive,brief ischemic episodes conducted during early reperfusion after prolonged coronary artery occlusion,a phenomenon termed "ischemic postconditioning".Anesthetic postconditioning,i.e.ischemic postconditioning is elicited by anesthetic administration right at the onset of reperfusion,is another promising therapeutic strategy of attaining myocardial protection against ischemia-reperfusion damage.For example,isoflurane postconditioning reduced myocardial infarct size by activation the pro-survival phosphatidylinositol-3-kise(PI3K)-Akt signaling cascade and preventing opening of MPTP through inhibition of glycogen synthase kinase 3β. Sevoflurane had been demonstrated to exert cardioprotection via many pathways during ischemia reperfusion14-17.However,whether their postconditionings are associated with MPTP is still unclear.Sevoflurane,a volatile anesthetic,was demonstrated to have cardioprotective effect in ischemic and reperfused rat hearts by postcontioning.Obal et al.had elucidated that the adenosine triphosphate-sensitive potassium(KATP)channel did involve the postconditioning of sevoflurane21,which was in line with our previous results.Nevertheless,it might not be the only mediator underlying the complicating pathological lesion.Glyburide,a KATPantagonist, pretreatment significantly attenuated the recovery of left ventricular developed pressure(LVDP),but did not abolish the cardioprotection observed with sevoflurane15. The recovery of LVDP and left ventricular end-diastolic pressure(LVEDP)in sevoflurane-treated hearts was slightly quicken in onset as compared with pinacidil,a KATPchannel opener15.Opening of KATPchannel was unlikely to represent the sole mechanism of protection produced by sevoflurane.Taken together,the mechanism undergoing postconditioning of sevoflurane and against referfusion injury is not well established.Due to the important role of MPTP during reperfusion injury,in the present study,we used atractyloside(ATR),a MPTP opener,to investigate the relationship between MPTP and postconditioning of sevoflurane.Objective:To observe protective effect and Mechanisms of Sevoflurane postprocessing in myocardial ischemia/reperfusion in isolated rat hearts.Methods:Applying Langendorff perfusing system to establish myocardial ischemical reperfusion injury model in Rat ex vivo.24 models were randomly divided into four groups(n=6):control group(CON),ATR(Atractyloside)group,Sevoflurane postprocessing(SPC)group,and SPC+ATR group.All drugs were given in the initial 15 minutes of reperfusion.Change of hemodynamics was monitered in the experiment, the limit of myocardial infarction was determined by 1%of tetrazolylazo salt(TTC).Results:Compared to CON group,SPC group attenuated depressant effect of ischemical reperfusion on left ventricular developed pressure(LVDP),left ventricular end -diastolic pressure(VEDP),maximum systolic/ diastolic rate(±dp/dtmax),left ventricular developed pressure with heart rate(LVDP×HR)(when the time for reperfusion=60 min,P＜0.05)and degraded myocardial infarct size(IS)(P＜0.05); but in SPC+ATE group ATR group,there was no statistical diference compared to CON group.Conclusion:Postconditioning of sevoflurane could relieve cardiac ischemia-reperfusion injury,mitochondfial permeability transition pore(MPTP)participate and mediate myocardial preservation effect. |
