Protective Effects Of Epidural Injection With Morphine On Acute Myocardial Ischemia And Reperfusion Injury In Rabbits

Morphine is a central analgesic and sedative. It has the effects of analgesia, restraining the activity of sympathetic nerve, lessening the preload and afterload of heart, cutting down the oxygen consumption of myocardium and it is a commonly used drug in treating acute myocardial infarction. In recent years, it was discovered that morphine could mimic IPC, limit infarction size after infarction and thus protect the myocardium. The study was designed to investigate the protective effects of epidural injection with morphine in the rabbits' model of acute myocardial ischemia and reperfusion injury in respects of myocardial infarct size, myocardial apoptosis and the left ventricular function.Part A: The rabbit opening thorax and LAD ligation model was created to present acute myocardial ischemia and reperfusion. Twenty-two New Zealand rabbits were assigned randomly into two groups: epidural morphine group and control group. The thoracotomy was performed and the pericardium was opened to expose the heart. The left anterior descending(LAD) coronary artery was occluded for 30 min, and followed by a four-hour reperfusion. Either morphine(0.25mg/kg, 0.5ml) or normal saline 0.5ml were injected epidurally in corresponding group over a period of 2 min 20 min before coronary artery occlusion. The myocardial enzyme CK-MB and cTNT were monitored. The myocardial area at risk and the infarct area were determined with Evans blue dye and triphenyl tetrazolium chloride(TTC), and the infarct size was measured. The results showed both serum CK-MB and cTNT had no difference between the two groups before the coronary artery was occluded. After a four-hour reperfusion, both serum CK-MB and cTNT increased significantly in two groups, but the elevation of serum CK-MB (7656.6±1567.5 U/L)and cTNT(0.169±0.039 ng/ml) in epidural morphine group were significantly lower than that in control group(5355.8±1352.2 U/L ^P 0.12±0.053 ng/ml), the difference had statistical significant. After a four-hour reperfusion, myocardial infarct size of epidural morphine group as a percentage of the risk zone and the left ventricle size were much lesser than that of control group (IS/AAR: 26.1±5.3% vs 43.9±8.1%, IS/LVS: 7.0±2.8% vs 11.6±3.5%) , with the significant statistical differences (PO.01).Part B: Twenty-two rabbits were divided randomly into two groups : epidural morphine group and control group. The animal model and the surgical procedure were similar to that of the part one. After a four-hour reperfusion, a piece of myocardial tissue was taken from the risk zone for determination of the apoptotic myocyte count in 200 myocardial cells (TUNEL). The results suggested that the apoptotic myocyte count of the epidural morphine group was less compared with that of the control group (60.6±7.5 vs 85.7±9.2) , the difference had statistical significant (P<0.05). The percentage of the apoptotic myocytes of the epidural morphine group was 30.3%, and that of the control group was 42.5%, the difference had statistical significant (P<0.05).Part C: Twenty-four rabbits were assigned randomly into two groups : epidural morphine group and control group. The animal model and the surgical preparation of the two groups were similar to that of the part one. But the thoracic cavity of the rabbits was closed up and the rabbits were surviving. Echocardiographic assessment was undertaken 4 weeks after myocardial infarction and reperfusion. Echocardiography suggested that the LVESD and LVEDD in the two groups increased significantly, but that was more pronounced in control group(P<0.05);meanwhile, the LEVF and LVFS in two groups decreased significantly(9.36% and 8.24% in the epidural morphine group, 13.53% and 12.18% in the control group, respectively) , but it's more obvious in control group(P<0.05).The heart function of left ventricle of the epidural morphine group was better than that of the control group (LVEF:69.73% vs 62.99%;LVFS:31.39% vs 26.59%;LVEDD: 14.35% vs 16.96;LVESD:9.52 vs 12.01 ), the difference had statistical significant (P<0.05).Conclusion Epidural injection with morphine can reduce myocardial enzyme release, the apoptotic myocyte count and limit myocardial infarction size.It also can improve the heart function after myocardial infarction and reperfusion. Epidural injection with morphine can effectively protect the myocardium from the injury of infarction and reperfusion.