瑞芬太尼预处理对大鼠心肌缺血再灌注损伤的影响

Protective effect of remifentanil precondition on myocardium against ischemia/reperfusion injury in rats

目的观察瑞芬太尼预处理对大鼠心肌缺血再灌损伤的影响。方法建立50只大鼠心肌缺血再灌注损伤模型。随机分为对照组(CON组)、缺血预处理(IPC)组和瑞芬太尼预处理(RPC) 组,RPC组根据瑞芬太尼不同给药剂量又分为RPC1、RPC2、RPC3、RPC4、RPC5组,分别以0.2、0.6、2、6 和20μg·kg-1·min-1速率静脉泵注5 min,停止5 min,重复进行3次。于缺血前30 min、缺血30 min、再灌注120 min时记录心电图、收缩压、平均动脉压(MAP)、HR,计算收缩压与HR乘积(RPP)。再灌注120min时取出大鼠心脏,称心脏湿重,并制作心肌病理切片,计算左心室(LV)、右心室(RV)、缺血危险区(AAR)和梗死区(IS)的面积及体积,计算LV与RV体积之和、IS面积与AAR面积之比(IS/AAR)。结果与CON组比较,RPC2、RPC3、RPC4和RPC5组缺血30 min时MAP降低(P<0.05)。IPC、RPC1、RPC2、RPC3、RPC4、RPC5组IS和IS/AAR降低(P<0.05或0.01),心脏湿重、LV与RV体积之和、AAR 体积差异无统计学意义(P>0.05)。各组HR、RPP比较差异无统计学意义(P>0.05)。瑞芬太尼剂量-效应关系Sigmoidal方程为:Y=15.18+17.76/[1+10(-2.75-X)],ED50为2.689μg·kg-1·min-1。结论瑞芬太尼可模拟心脏缺血预处理作用,对心肌缺血再灌注损伤具有保护作用。

Objective To study the effect of remifentanil precondition on myocardium against ischemia/reperfusion （I/R） injury. Methods Fifty male SD rats weighing 300-350 g were anesthetized with intraperitoneal 5% pentobarbital 40 mg· kg^-1 , tracheostomized and mechanically ventilated. Right carotid artery and jugular vein were cannulated for BP monitoring and drug administration. ECG, BP and HR were monitored continuously. The chest was opened and heart exposed via a left thoracotomy. A 6-0 prolene suture was placed around the left coronary artery and a snare was made. The coronary artery was occluded by tightening the snare. Myocardial ischemia was confirmed by the appearance of a regional cyanosis of myocardium, decrease in BP and ST-T changes on ECG. After the surgical procedure a 15-minute stabilization period was allowed. The animals were then randomly divided into 3 groups： Ⅰ control group （CON, n = 9） ; Ⅱ ischemic preconditioning group （IPC, n = 9）and m remifentanil preconditioning group which was further divided into 5 subgroups according to the dose of remifentanil （RPC）. In control group the hearts were subjected to 30 min ischemia followed by 120 min reperfusion,（I/R）. In IPC group the hearts were subjected to 3 episodes of 5 min ischemia in succession at 5 min interval for reperfusion before I/R. In RPC group the animals received 3 periods of 5 rain remifentanil infusion at 0.2 （ RPC1 ,n=5）, 0.6 （RPC2,n =6）, 2 （RPC3 ,n=8）, 6 （RPC4 ,n=7） or 20 （RPC5 ,n=6）μg·kg^-1·min^-1 at 5 min interval before I/R. MAP, HR and RPP （SP × HR） were recorded before and after I/R. Infarct size （IS） and the area at risk （AAR） were determined by triphenyhetrazolium staining. Results MAP was significantly lower at the end of 30 min ischemia in RPC2, RPC3, RPC4 and RPC5 subgroups than in control group. There was no significant difference in MAP, HR and RPP at the end of 120 min reperfusion among the 3 groups. The infarct size was significantly smaller in IPC and RPC groups than in control group. RPC at 6 μg· kg^-1 . min^-1 provided best protective effect. The sigmoidal equation of the dose-effect curve was Y = 15.18 ＋ 17.76/[ 1 ＋ 10^（ -257- X） ]. ED50 was 2.689 μg· kg^-1· min^-1 . Conclusion Remifentanil and IPC have similar protective effect on the heart against I/R injury.