Effects of morphine preconditioning on myocardial ischemia-reperfusion injury and phosphorylated extracellular signal-regulated kinase 1/2 expression in rats wRh chronic heart failure

Abstract

Objective To investigate the effects of morphine preconditioning on myocardial ischemiareperfusion (I/R) injury and the expression of phosphorylated extracellular signal-regulated kinase 1/2 (p-ERK1/2)in rats with chronic heart failure.Methods Forty-eight healthy male SD rats weighing 220-250 g were randomly divided into 6 groups ( n =8 each):control group (group C),sham operation group (group S),I/R group and preconditioning with low,median and high doses of morphine groups (groups MP1-3 ).Chronic heart failure was induced by iv edriamycin 2.0 mg/kg once a week for 6 weeks in groups S,I/R and MP1-3.Left ventricular end-diastolic diameter (LVEDD) and left ventricular end-systolic diameter (LVESD) were measured using ultrasound,and left ventricular ejection fraction (LVEF) and left ventricular fractional shortening (LVFS) were calculated at the end of 14th day after the end of adriamycin administration.Blood samples from the carotid artery were collected after ultrasonography for determination of the plasma brain natriuretic peptide (BNP) concentration.Myocardial I/R was induced by 30 min occlusion of left anterior descending branch of coronary artery followed by 120 min reperfusion at 2 day after ultrasonography in groups I/R and MP1-3.In groups MP1-3,iv morphine 0.015,0.030 and 0.050 mg/kg were repeated 3 times at 5 min interval at 30 min before ischemia respectively,while normal saline 5 ml/kg was given in group I/R.The animals were sacrificed at the end of reperfusion in groups S,I/R and MP1-3,and the hearts were removed to measure the area at risk (AAR),infarct size (IS),and IS/AAR ratio was calculated.The p-ERK1/2 expression in myocardium was assessed by Western blot.Results The LVESD and plasma BNP concentration were significantly higher,while the LVEF and LVFS lower in the other 5 groups than in group C (P ＜0.01).No myocardial infarction was found in group S.The p-ERK1/2 expression was significantly lower in groups I/R and MP1 than in group S (P ＜ 0.05).IS and IS/AAR ratio were significantly lower,and p-ERK1/2expression was significantly higher in groups MP2.3 than in group I/R ( P ＜ 0.05).There were no significant differences in IS,IS/AAR ratio and p-ERK1/2 expression between groups MP1 and I/R (P ＞ 0.05).IS and IS/AAR ratio were decreased gradually,and the p-ERK1/2 expression was up-regulated gradually in groups MP1-3 ( P ＜0.05).Conclusion Morphine preconditioning can confer cardioprotection against myocardial I/R in a dose-dependent manner in rats with chronic heart failure.Up-regulation of p-ERK1/2 expression is involved in the underlying mechamism. Key words: Morphine; Ischemic preconditioning; Myocardial reperfusion injury; Heart failure; Extracelluiar signal-regulated MAP kinases