| Objective Sufentanil , having small impact on blood dynamics, efficient and ease the role of the characteristics, such as it is now widely used in clinical, especially applies to cardiovascular surgery narcotic needs. There are less research studies of sufentanil delayed preconditioning on the myocardium damage and the mechanism around the world. The purpose of this study was to investigate the effect of sufentanil delayed preconditioning against ischemia reperfusion injury in rat heart and its mechanisms.Methods Male SD rats, weighing 250～330 g underwent 30 min ischemia followed by 120 min reperfusion and the ischemia reperfuion injury model were elicited by occlusion and open of LAD. The study contained two parts: First, to investigate the effect of sufentanil delayed preconditioning on ischemia reperfusion injury heart in rats, 42 rats were randomly assigned to 7 groups (n=6 each): (CON), rats were received preconditioning with 0.9% NS 2ml, 30 min infusion via tail vein to maintain a constant speed at 24h before myocardial ischemia. (DIPC), rats were received preconditioning by ischemia ( 5-min of LAD occlusion , 5-min reperfusion×3) . (SFPC), according to size by different rats were divided into 5 groups (SFPC3μg, SFPC15μg, SFPC30μg, SFPC60μg, SFPC120μg), the rats were received preconditioning with sufentanil (3μg/kg,15μg/kg,30μg/kg,60μg/kg,120μg/kg) ,30 min infusion by iv at 24 h before myocardial ischemia. MAP and HR were recorded before a 30 min stabilization, at the end of ischemia and at the end of reperfusion. RPP was calculated. Arterial blood samples were obtained immediately at the end of reperfusion to determine plasma concentration of cTnI. Then the animals were sacrificed and myocardial tissues were obtained to determine IS and AAR .Second, to evaluate the role of iNOS in the delayed cardioprotection induced by sufentanil preconditioning in rats.30 adult male SD rats, weighing 250～330g, were randomly divided into 5 groups (n=6 each): (Sham),sham operation group, rats were received no occlusion or reperfusion,(CON), rats were received preconditioning with 0.9% NS 2ml, 30 min infusion by iv at 24 h before myocardial ischemia. (SFPC120μg), rats were received preconditioning with sufentanil 120μg/kg, 30 min infusion by iv at 24 h before myocardial ischemia.(SFPC120μg +SMT), sufentanil preconditioning + a specific iNOS inhibitor group , rats were received preconditioning with sufentanil 120μg/kg by iv at 24 h before the LAD occlusion and 10mg/kg SMT was administered at 10 min before myocardial ischemia.(SMT), 10mg/kg SMT was administered by iv at 10 min before the LAD occlusion. MAP and HR were recorded before a 30 min stabilization, at the end of ischemia and at the end of reperfusion. RPP was calculated. Arterial blood samples were obtained immediately at the end of reperfusion to determine plasma concentration of NO. Then the animals were sacrificed and myocardial tissues were obtained to determine IS, AAR and the myocardial levels of iNOS protein expression.Results Blood dynamics part 1: There was no significant difference in blood dynamics among the groups (P>0.05). part 2: MAP and RPP were significantly lower at the end of 120 min reperfusion in CON group, SFPC120μg group, group and (SFPC120μg +SMT) group SMT than that in Sham group (P<0.05). MAP and RPP were significantly lower at the end of ischemia in CON group and SMT group than that in Sham group (P<0.05). There were no significant differences in HR, MAP and RPP among the groups except the Sham group (P>0.05). IS/AAR and cTnI part 1: There were no significant differences in (LV+RV), AAR, AAR/(LV+RV) among the groups (P>0.05). Compared to CON group, the infarct size (IS/AAR) and plasma concentration of cTnI were significantly less in SFPC15μg,SFPC 30μg,SFPC 60μg,SFPC 120μg groups and DIPC group(P<0.05).Compared with SFPC15μg group,the IS/AAR and cTnI concentration were significantly less in SFPC30μg,SFPC60μg,SFPC120μg groups and DIPC group(P<0.05). There were no significant differences in IS/AAR and cTnI concentration among the groups of SFPC30μg group,SFPC60μg group ,SFPC120μg group and DIPC group(P>0.05). part 2: There were no significant differences in (LV+RV), AAR, AAR/(LV+RV) among the groups (P>0.05).Compared with CON group, there was no significant difference in IS/AAR in (SFPC120μg+SMT) group and SMT group (P>0.05). IS/AAR was significantly lower in SFPC120μg group than that in CON group(P<0.05). NO concentration and iNOS protein expression Compared with CON group, there was no significant difference in plasma concentration of NO in (SFPC120μg+SMT) group and SMT group (P>0.05). Plasma concentration of NO and iNOS protein expression were higher in group SFPC120μg than that in group CON(P<0.05).Conclusion Like DIPC, pretreatment with sufentanil at dose of 15,30,60 and 120μg/kg in intact rat induces a dose related delayed cardioprotection . SFPC30μg group might exert optimal protective effect among SFPC groups. The sigmoidal equation of the dose-effect curve was Y=24.19+35.88/[1+10(-3.336-x)]. EC50 was 0.461μg·kg-1·min-1. iNOS maybe mediates the sufentanil-induced delayed cardioprotection. |
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