芬太尼与瑞芬太尼预处理抗大鼠体外心肌缺血-再灌注损伤作用比较

Comparison of Protective Effects of Fentanyl and Remifentanil Preconditioning on Myocardium against Ischemia-Reperfusion Injury in Rats

目的比较芬太尼与瑞芬太尼预处理对大鼠体外心脏功能及心肌缺血·再灌注损伤后的影响。方法雄性sD大鼠50只，体重200-250g，随机分为5组，麻醉后开胸取心脏，建立Langendorff大鼠体外心脏灌注模型。每组均灌注平衡20min。对照组（CON）用95％氧气和5％二氧化碳饱和的K—H液持续灌注20min，停灌30min再灌注45rain。芬太尼预处理组（FPCI，FPC2）：缺血前用含芬太尼20或40μg·L^-1的95％氧气和5％二氧化碳饱和K—H液灌注20min，全心缺血30min，复灌45min。瑞芬太尼预处理组（RPC1，RPC2）：瑞芬太尼浓度及灌注方法同芬太尼组。记录各组左室舒张米压（LVEDP）、左室收缩压（LVSP）及冠状动脉流量（CF）变化，测定平衡15min后到再灌注后15min内冠状动脉流出液乳酸脱氢酶（LDH）活性，测定再灌注后45min时的心肌丙二醛（MDA）含量，同时取每组大鼠心肌做切片，在电镜下观察心肌细胞的超微结构。结果在平衡20min末，各组LVEDP，LVSP以及LDH的活性比较差异无显著性。与对照组比较，芬太尼及瑞芬太尼预处理组在灌注后各时间点LVEDP降低（均P〈0．01），LVsP及CF升高（均P〈0．01），灌注后15min冠脉流出液LDH活性降低（均P〈0．01），再灌注后45min后心肌MDA含量降低（均P〈0．01），梗死面积较小（均P〈0．05），电镜下心肌结构破坏不明显；组内比较，高浓度处理组保护作用明显（P〈0．05）；组间比较瑞芬太尼组保护作用较好（P〈0．05）。结论芬太尼和瑞芬太尼对体外大鼠全心缺血-再灌注损伤均有保护作用，且有浓度依赖性，相同浓度的瑞芬太尼与芬太尼比较保护作用更明显，二者对体外心肌心功能影响无差别。

Objective To compare the cardioprotective effects of fentanly and remifentanil pretreatment against rat myocardial ischemia reperfusion injury. Methods 50 male SD rats were randomly divided into 5 groups. After anesthesia, the hearts were immediately removed out to establish the Langendorff isolated heart perfusion model. After 20 min of perfusion for stabilization in each group, the hearts were consistently perfused with 95% 02 saturated K-H solution for 20 min, and subjected to 30 min global ischemia by suspension followed by 45 min reperfusion in the control group. In the fentanyl pretreatment groups （ FPC 1, FPC2 group） and remifentanil pretreatment group （ RPC 1, RPC2 group）, the hearts were perfused with 20 or 40μg·L^-1 drugs before ischemia-reperfusion respectively. The left ventricular systolic pressure （ LVSP）, left ventricular and diastolic pressure （LVEDP） and coronary flow （CF） were monitored continuously. Coronary effluent was collected from 15 min of stabilization to 15 min of reperfusion and the LDH activity was determined. At the end of 45 min reperfusion,the hearts were removed for determining the myocardial MDA content. Meanwhile, the heart sections were cut to examine the uhrastructure by using electron microscopy. Results At the end of stabilization for 20 min, LVEDP, LVSP and LDH activity were showed no significantly change in each group. During perfusion, LVEDP in the fentanyl and remifentanil pretreatment group significantly decreased （ P 〈 0.01 ） compared with the control group, LVSP and CF increased（ P 〈 0.01 ）, LDH reduced 15 min after perfusion, the myocardial MDA content was significantly lower （P 〈 0.01 ） 45 min after perfusion, the infarct area was significantly smaller （ P 〈 0.05 ） and the myocardial ultrastructure was well-preserved. Higher concentration of fentanyl or remifentanil showed better cardioprotective effects（ P 〈 0.05 ）. Compared with fentanyl, remifenanil displayed more cardioprotective effects（ P 〈 0.05 ）. Conclusion Both fentanyl and remifentanil have dose-depended protective effects on myocardial ischemia reperfusion, and remifentanil is better than fentanyl in the same concentration. No different effects are found between two drugs on the mechanical function of isolated myocardial in rats.