The effect of sevoflurane preconditioning on cytochrome C release from mitochondria during ischemia/reperfusion in isolated rat hearts

Objective To explore the effect of sevoflurane preconditioning on cardiocyte apoptosis and cytochrome C release from mitochondria during ischemia/reperfusion in isolated rat hearts.Methods Forty male Sprague-Dawley rats weighing 250 g-300g were randomly divided into 4 groups (n=10 for each group):control group (C); 3 different concentrations of sevoflurane preconditioning groups of 0.75％ (S1 ),1.5％ (S2),3.0％ (S3) sevoflurane respectively.All of the isolated rat hearts were retrogradely perfused via aorta with Krebs-Henseleit (K-H) solution on Langendorff apparatus.The isolated hearts were subjected to ischemia for 30 min followed by 60 min reperfusion.Hearts in the S1,S2,S3 groups were preconditioned by perfusing with K-H solution which containing 0.75％,1.5％,3.0％ sevoflurane respectively for 10 min and then followed by 5 min K-H solution washout before ischemia.The preconditioning procedure was repeated twice.Hemodynamics of the hearts were recorded after equilibration (baseline values),immediately before ischemia,30 and 60 min after reperfusion respectively.Apoptotic myocardial cells were detected by terminal deoxynucleotidyl transferase-mediated dUTP nick end labelling (TUNEL) and the level of cytochrome C expression in myocardial cytosol and mitochondria was measured by Western Blot at the end of reperfusion.Results At the end of 30 and 60 min reperfusion,left ventricular end-diastolic pressure (LVEDP) was significantly lower and left ventricular developed pressure (LVDP)was significantly higher in S1,S2,S3 groups than those in C group (P＜0.05).Apoptotic index decreased significantly in S1,S2,S3groups compared with C group at the end of reperfusion (P＜0.05,P＜0.01) and the apoptotic index of C,S1,S2,S3 groups was (33.10±2.57)％,(28.03±3.11)％,(25.20±3.04)％,(24.06±2.58)％ respectively.Cytochrome C level increased significantly in mitochondria but decreased significantly in cytosol in S1,S2,S3 groups as compared with C group (P＜0.05,P＜0.01 ).Conclusions Sevoflurane preconditioning decreased cardiocyte apoptosis,protected the heart against ischemia/reperfusion injury by attenuatiing the release of cytochrome C from mitochondria to cytosol. Key words: Sevoflurane preconditioning ;  Ischemia/reperfusion injury ;  Apoptosis ;  Cytochrome C ;