Delayed cardioprotection of different doses of sufentanil preconditioning in rats

Objective To investigate the delayed cadioprotection of different doses of sufentanil preconditioning and its dose-dependent relation.Methods Forty-two adult male Wistar rats,weighing 250-300 g,were randomly divided into 7 groups (n = 6 each).Twenty-four hours before myocardial ischemia,in group Ⅰ ,rats were treated with intraperitoneal (IP) normal saline 1 ml/kg;in group Ⅱ ,Ⅲ,Ⅳ and Ⅴ ,rats were treated with 4 different doses of IP sufentanil 1,5,10 and 20 μg/kg respectively;in group Ⅵ and Ⅶ,rats were treated according to the same experimental protocols as those in group Ⅴ and Ⅰ respectively in addition to receiving nonselective opioid receptor antagonist naloxone 1 mg/kg IP 15 min before preconditioning with sufentanil 20 μg/kg or normal saline.Myocardial ischemia was induced by occlusion of left anterior descending coronary artery for 45 min followed by 120 min reperfusion.HR and MAP were recorded before ischemia and every 15 min during myocardial ischemia and reperfasion period.The rate-pressure product(RPP) was calculated.The blood samples from right internal carotid artery were obtained for determination of serum activity of CK-MB immediately before ischemia,and at 45 min of ischemia and 120 min of reperfusion.Hearts were removed to measure the left ventricle area (LVA) the myocardial infarct area (IA) and the area at risk (AAR) at 120 min of reperfusion and AAR/LVA and IA/AAR were calculated.Results There were no significant differences in HR,MAP and RPP at every measurement point during the experiment among all groups.As compared to group Ⅰ ,serum CK-MB activity was significantly decreased in group Ⅲ at 120 min of reperfusion and in group Ⅳ and Ⅴ at 45 min of ischemia and 120 min of reperfusion,and IA/AAR was decreased in group Ⅲ ,Ⅳ and Ⅴ .The serum CK-MB activity at 45 min of ischemia and 120 min of reperfusion and IA/AAR were significantly lower in group Ⅲ ,Ⅳ and Ⅴ than in group Ⅱ ,and in group Ⅳ and Ⅴ than in group Ⅲ.The senun activity of CK-MB at 45 min of ischemia and 120 min of reperfusion and IA/AAR were significantly higher in group Ⅵ than in group Ⅴ.There was no significant difference in AAR/LVA among all groups.Conclusion Sufentanil preconditioning can produce delayed cardiopretoction through activating opioid receptors in a dose-dependent manner,but there is celling effect. Key words: Sufentanil; Ischemic preconditioning; Myocardial reperfusion injury