Effect of sevoflurance postconditioning on cardiac function and ERK1/2 of isolated rat heart with acute myocardial ischemia-reperfusion injury

Aim To investigate the effect of sevoflurane postconditioning on cardiac function and activation of ERK1/2 in isolated rat hearts with acute myocardial ischemia reperfusion injury and to explore the possible myocardial preservation mechanism involved.Methods In protocol 1,64 SD rats were randomly divided into 8 groups(n=8 for each group).Except Sham group,Langendorff perfused rat hearts subjected to 30 min ischemia followed by 90 min reperfusion were assigned to untreated(control),four cycles of postconditioning ischemia(25 s of each),3.0 V/V sevoflurane postconditioning(for 5 min and 10 min of washout),and the PD98059 solvent DMSO(0.2%),ERK1/2 inhibitor PD98059(20 μmol·L-1),and Post+PD,Sevo+PD(coadministration).Left ventricular diastolic pressure(LVEDP),left ventricular developed pressure(LVDP),heart rate(HR),coronary flow(CF),+dp/dt and-dp/dt at 30 min of equilibrium,30,60,90 min of reperfusion were recorded,respectively.Acute infarct size was measured by triphenyltetrazolium chloride staining.In protocol 2,after 15 min reperfusion,the expression of total and phosphorylated forms of ERK1/2 and its downstream target p70S6K were determined by Western blot.Results No differences in baseline hemodynamics were observed among the experimental groups(P0.05).After reperfusion,compared with control group,Sevo group and Post group significantly(P0.05)improved functional recovery and largely(P0.05)decreased myocardial infarct size(24.1%±3.5%,22.7%±3.2%,vs 41.7%±5.1%,both P0.05),and at the 15 min of reperfusion,obvious(P0.05)upregulation of the expression of phosphorylation ERK1/2 and p70S6K was also caused.Inhibiting the sevoflurane-induced phosphorylation of ERK1/2 at reperfusion with the ERK1/2 inhibitor PD98059 abrogated Sevoflurane-induced myocardial protection(38.4%±5.4% and 24.1%±3.5% for Sevo+PD98059 and Sevo,respectively,P0.05).Conclusions Sevoflurance postconditioning effectively protects against myocardial ischemia-reperfusion injury similar to ischemia postconditionding.Specifically,sevoflurance postconditioning and ischemia postconditionding protect the heart by activating ERK1/2 in vitro.