Role Of MPTP Mediated Oncosis In Sevoflurane Postconditioning Protects Rat Hearts In Vivo Against Ischemia-reperfusion Injury

ObjectiveTo investigate the role of MPTP (mitochondrial permeability transition pore) mediatedoncosis and apoptosis in sevoflurane postconditioning protects rat hearts in vivo againstmyocardial ischemia/reperfusion (I/R) injury.MethodsMale Sprague-Dawley rats, weighing280-360g, were randomly divided into fivegroups (n=21each): sham operation group (group SHAM), group I/R, sevofluranepostconditioning group (group SEVO), atractyloside+sevoflurane postconditioning group(group ATR+SEVO) and atractyloside group (group ATR). Myocardial ischemia wasinduced by30min occlusion of left anterior descending branch (LAD) of coronary arteryfollowed by2h reperfusion. With the exception of group SHAM, each group wassubjected to occlusion for30min followed by reperfusion for2h.2.5%sevoflurane wasinhaled for5min starting from27min of ischemia until2min after beginning ofreperfusion in SEVO and ATR+SEVO groups, while33%oxygen was inhaled in the othergroups. In ATR+SEVO and ATR groups, atractyloside5mg/kg was injected via theinternal jugular vein at15min before ischemia. The rats’ hemodynamic changes werecontinuously monitored and recorded. At the end of2hours’ reperfusion, the rats weresacrificed and the hearts removed for determination of myocardial infarct size. Themyocardial ultrastructure was observed by electron microscopy; the expressions of Porimin(Pro-oncosis receptor inducing membrane injury), cytochrome C (CytC) and cleavedCaspase-3were measured by Western Blot; myocardial nicotinamide adenine dinucleotide(NAD+) content were determinated by spectrophotometric. ResultsCompared with group SHAM, the MAP and RPP at1and2h reperfusion wasdecreased，the myocardial infarct size was enlarged, cardiocytes damage was increased, theexpression of Porimin, CytC and cleaved Caspase-3was up-regulated, and NAD+contentwas decreased in the other four groups (P<0.05). Compared with group I/R, the infarct sizewas decreased, cardiocytes damage was decreased, the expression of Porimin, CytC andcleaved Caspase-3was down-regulated, and NAD+content was increased in group SEVO(P<0.05). Compared with the SEVO group, the myocardial infarct size was enlarged,cardiocytes damage was increased, the expression of Porimin, CytC and cleaved Caspase-3was up-regulated, and NAD+content was decreased in the ATR+SEVO group (P<0.05).ConclusionSevoflurane postconditioning protects rat hearts in vivo against myocardial I/R injury,which may be through inhibiting MPTP opening, thereby inhibiting cell oncosis andapoptosis during reperfusion.