A Comparative Study Of Alprostadil Injection Between One Dose And Two Dose Administration On Myocardial Ischemia-reperfusion Injury In Rats

Objective: To compared the protective effect of alprostadil injection between one dose and two dose administration on myocardial ischemia reperfusion in rats. And to find the appropriate time for application.Methods: 576 female Wistar rats were randomly divided into for 6 groups, 12 rats in each group. The rats were anesthetized with ether. Myocardial I/R was induced as follows: The rats were placed in the supine position and secured in a dissection tray. A left thoracic incision was made to expose the heart, and myocardial ischemia was induced by making a slipknot(4-0 silk)around the left anterior descending coronary artery. After 120 min of ischemia, the slipknot was released and the myocardium was reperfused for10 min, 20 min, 30 min, 45 min, 60 min and90min. The rats in the sham group underwent the same surgical procedures with the exception of occlusion of the left anterior descending coronary artery. Sham operation group and model group were intravenous injection and sodium chloride injection(5 mg/kg), alprostadil injection group were given intravenous injection of alprostadil injection 4 g / kg, positive drug group were given intravenous injection of tirofiban 180 μg/kg. Alprostadil injection to take two administration: 1the rats were administrated alprostadil injection by intravenous for one times after ligation; 2the rats were administrated alprostadil injection by intravenous for two times after ligation and reperfusion, give medicine volume of 0.2 ml / 100 g body weight.At the end of reperfusion each group was tested: ischemia(ischemia area / left ventricular area),infarct size(ischemia / infarction area of the total area) and no reflow range(no reflow range /total ischemic range).Results: 1Compared with sham operation group, ischemia range, infarct size and no reflow area increased significantly in model group(P<0.01 or P<0.001). Compared with the model group, alprostadil injection one or two dose can significantly reduce the ischemia range, infarctsize and no reflow area(P<0.05 or P<0.01); 2Compared with the model group, alprostadil injection was administrated one dose after the ligation can significantly reduce myocardial ischemia range at different time of reperfusion 10 min, 20 min, 30 min, 45 min, 60 min and 90 min. The reduced the myocardial ischemia range were 69.67%, 82.35%, 61.50%, 50.87%,62.89% and 57.68% respectively; 3Compared with the model group, alprostadil injection was administrated one dose after the ligation can significantly reduce the myocardial infarction area at different time of reperfusion 10 min, 20 min, 30 min, 45 min, 60 min and 90 min. The reduced myocardial infarction area were 55.05%, 49.07%, 48.38%, 48.66%, 40.96% and43.46% respectively; 4Compared with the model group, alprostadil injection was administrated one dose after the ligation can significantly reduce myocardial no reflow range at different time of reperfusion 10 min, 20 min, 30 min, 45 min, 60 min and 90 min. The reduced myocardial no reflow range were 39.53% 57.63%, 45.82%, 52.41%, 11.71% and 34.15%respectively; 5Compared with the model group, alprostadil injection was administrated two dose can significantly reduce myocardial ischemia range at different time of reperfusion 10 min,20 min, 30 min, 45 min, 60 min and 90 min. The reduced the myocardial ischemia range were45.61%, 49.12%, 43.92%, 44.03%, 66.07% and 45.38% respectively; 6Compared with the model group, alprostadil injection was administrated two dose can significantly reduce the myocardial infarction area at different time of reperfusion 10 min, 20 min, 30 min, 45 min, 60 min and 90 min. The reduced myocardial infarction area were 37.94%, 38.09%, 31.81%,51.15%, 43.34% and 41.48% respectively; 7Compared with the model group, alprostadil injection was administrated two dose can significantly reduce myocardial no reflow range at different time of reperfusion 10 min, 20 min, 30 min, 45 min, 60 min and 90 min. The reduced myocardial no reflow range were 47.72%, 48.22%, 37.31%, 44.03%, 49.30% and 43.55%,respectively.Conclusion: Alprostadil injection have the protective effect of myocardial ischemia reperfusion.The protective effect of one dose of alprostadil injection at reperfusion 20 min is better than other time. Our results indicate that the main protective effect of alprostadil injection play a rolein the early phase of reperfusion.