Effects of sevoflurane postconditioning on ischemia-reperfusion injury in chronically-infarcted rat hearts / 中华麻醉学杂志

ABSTRACT

Objective To evaluate the effects of sevoflurane postconditioning on ischemia-reperfusion injury in chronically-infarcted rat hearts.Methods Left anterior descending coronary artery was ligated to induce myocardial infarction in male Sperague-Dawley rats.Six weeks later,chronically-infarcted hearts were isolated and passively perfused in a Langendorff apparatus.Eighty chronically-infarcted hearts were randomized into 8 groups (n =10 each)∶ Ⅰ-Ⅷ groups.In group Ⅰ,hearts were continously perfused with Krebs-Henseleit (K-H) solution for 90 min.In group Ⅱ,hearts were subjected to 30 min of global ischemia,followed by 60 min of reperfusion.In groups Ⅲ to Ⅵ,hearts were exposed to 30 min of global ischemia,specific phosphatidylinositol-3-kinase (PI3K) inhibitor LY294002 15 μmol/L and mitogen-activated extracellular regulated kinase 1/2 (MEK1/2) inhibitor PD98059 20 μmol/L,0.02％ dimethyl sulfoxide,and K-H solution saturated with 3％ sevoflurane were administered,respectively,during the first 15 min of reperfusion,followed by perfusion with plain K-H solution for 45 min.In groups Ⅶ and Ⅷ,hearts were exposed to 30 min of global isehemia,K-H solution saturated with 3％sevoflurane was given during the first 15 min of reperfusion,LY294002 15 μmol/L and PD98059 20 μmol/L were simultaneously administered,respectively,followed by perfusion with plain K-H solution for 45 min.Coronary flow (CF),left ventricular developed pressure (LVDP),± dp/dt,left ventricular end-diastolic pressure (LVEDP) and heart rate (HR) were recorded after 20 min of equilibration (baseline,T0),immediately before ischemia (T1),and at 15,30 and 60 min of reperfusion (T2-4).The concentrations of lactate dehydrogenase (LDH) and creatine kinase-MB (CK-MB) in the collected coronary effluent were determined at T0 and T4.Acute myocardial infarct size was determined at T4.Left ventricular tissue samples were collected at T2 to measure the phosphorylation of protein kinase B/Akt (PKB/Akt),and extracellular regulated kinase 1/2 (ERK1/2) and degree of mitochondrial permeability transition pore (rnPTP) opening.Results Compared with group Ⅰ,LVDP,± dp/dt,HR and CF were significantly decreased,LVEDP was increased,the acute myocardial infarct size was enlarged,and the concentrations of LDH and CK-MB in the coronary effluent and degree of mPTP opening were increased during reperfusion in groups Ⅱ-Ⅷ (P ＜ 0.05).LVDP,± dp/dt,HR and CF were significantly higher,LVEDP was lower,the acute myocardial infarct size was smaller,the concentrations of LDH and CK-MB in the coronary effluent were lower,the phosphorylation of PKB/Akt and ERK1/2 was higher,and the degree of mPTP opening was lower during reperfusion in group Ⅵ than in group Ⅱ (P ＜ 0.05).Conclusion Sevoflurane postconditioning protects chronically-infarcted rat hearts against ischemia-reperfusion injury by activating PI3K-PKB/Akt and MEK1/2-ERK1/2 and inhibiting mPTP opening.