芬太尼后处理、肢体远隔缺血后处理和缺血后处理对大鼠心肌缺血／再灌注初期室性心律失常的影响

Effects of fentanyl postconditioning, remote ischemia postconditioning and ischemia postconditioning on ventricular arrhythmia during myocardial ischemia and initial reperfusion in rats

目的对比观察芬太尼后处理、远隔缺血后处理和缺血后处理3种干预措施抑制大鼠心肌缺血，再灌注初期室性心律失常作用的差别。方法将73只成年雄性SD大鼠（体重250g-350g）麻醉后按随机数字表法随机分为9组：空白对照组（s组，n=5）；对照组（C组，n=7）；芬太尼后处理组（F组，n=9）；肢体远隔缺血后处理组（R组，n=9）；缺血后处理组（P组，n=8）；联合应用芬太尼后处理和肢体远隔缺血后处理组（F-R组，n=9）；联合应用芬太尼后处理和缺血后处理组（F-P组，n=8）；联合应用肢体远隔缺血后处理和缺血后处理组（R-P组，n=9）；联合应用芬太尼后处理、肢体远隔缺血后处理和缺血后处理组（F-R-P组，n=9）。所有大鼠开胸后采用丝线套扎其冠状动脉左前降支（left anterior descending coronary artery，LAD）做成活结。除S组之外，所有大鼠接受局部心肌缺血30min和再灌注60min的处理。C组不采用任何干预措施；F组、F-R组、F-P组和F-R-P组在LAD结扎15min时缓慢静脉注射芬太尼30μg／kg；R组、F-R组、R-P组和F-R-P组在LAD结扎15min时结扎大鼠双下肢造成肢体缺血10min后恢复双下肢血流灌注；P组、F-P组、R-P组和F-R-P组开放实施再灌注的初期连续实施3个循环的开放LAD20s／阻断LAD20S的缺血后处理。记录缺血期和再灌期前30min内的心律失常评分（AS评分）以及室性心动过速（ventricular tachycardia，VT）和心室纤颤（ventricular fibrillation，VF）的发生率和持续时间。结果缺血期VT和VF的发生率、VT或VF的持续时间以及AS评分在C组、F组、R组、P组、F-R组、F-P组、R-P组和F-R-P组无统计学差异。C组、F组、R组、P组、F-R组、F-P组、R-P组和F-R-P组再灌注初期AS评分的中位数分别为4、2、2、1、2、1、1和2。与C组比较，其余各组再灌注初期室性心律失常发生显著减少；再灌注初期的VT持续时间和AS在F组和R组之间无统计学差异，但F-R组再灌注初期的VT持续时间则显著降低。与F组和R组比较，P组、F-R组、F-P组、R-P组和F-R-P组再灌注初期的VT持续时间和室性心律失常评分显著减低。结论与芬太尼后处理和远隔缺血后处理比较，缺血后处理可更有效抑制再灌注初期室性心律失常的发生。联合应用芬太尼后处理和远隔缺血后处理后，抑制心肌再灌注初期室性心律失常的作用相对增强。

Objective To investigate the effects of fentanyl postconditioning, remote isehemia postconditioning and ischemia postconditoning on ventricu]ar arrhythmias during myocardial ischemia and initial reperftzsion in rats. Methods Seventy-three anesthetized male SD rats （weighed 250 g to 350 g） were randomly allocated into nine groups： sham group （group S, n=5）, control group （group C, n=7）, fentanyl postconditioning group （group F, n=9）; remote postconditioning group （group R, n=9）, ischemia postconditioning group （group P, n=8）; combined fentanyl postconditioning and remote postconditioning group （group F-R, n=9）; combined fentanyl postconditioning and ischemia postconditioning group （group F-P, n=8）; combined remote postconditioning and ischemia postconditioning group （group R-P, n=9）; and combined all three methods group （group F-R-P, n=9）. Thoracotomy was performed in the rats, and the left anterior descending coronary artery （LAD） was encircled with a suture to make a snare. Except for the group S, in the other groups, LAD was ligated for 30 min （ischemia） followed by a 60 rain reperfusion （LAD open） in vivo. In group C, no additional intervention was performed. In groups F, F-R, F-P and F-R-P, fentanyl 30 μg/kg was slowly injected intravenously at 15 min after LAD ligation. In groups R, F-R, R-P and F-R-P, the bilateral hind limbs underwent a 10 min ischemia which started at 15 min after LAD ligation with tourniquet. In groups P, F-P, R-P and F-R-P, 30 min after LAD ligation, Ischemia postconditioning was done with successive three cycles of a 20 s LAD open followed by a 20 s LAD re-occlusion. During the periods of ischemia and the first 30 min of reperfusion, the arrhythmias score （AS）, the incidences and durations of ventricular tachycardia （VT） and fibrillation （VF） were recorded. Results There were no significant differences in the AS, incidences and durations of VT and VF during the periods of ischemia among groups C, F, R, P, F-R, F-P, R-P and F-R-P. The medians of AS during initial period of reperfusion in groups C, F, R, P, F-R, F-P, R-P and F-R-P were 4, 2, 2, 1, 2, 1, 1 and 2 respectively. During initial period of reperfusion, compared with group C, incidence of ventricular arrhythmia was significantly decreased in other groups; duration of both VT and AS did not significantly changed in groups F and R, but duration of VT was shorter in group F-R. As compared to groups F, R and F-R, duration of VT during initial period of reperfusion was significantly shorter, and AS was lower in groups P, F-P, R-P and F-R-P. Conclusions As compared with fentanyl postconditioning and remote postconditioning, ischemia postconditioning was more effective in anti-arrhythmia during initial period of reperfusion. Combined fentanyl postconditioning and remote postconditioning can produce an enhanced anti-arrhythmic effect during the myocardial ischemia-reperfusion process.