抗心律失常肽对兔心肌缺血再灌注心律失常的影响

Effects of antiarrhythmic peptide on ventricular arrhythmia in rabbits with ischemia-reperfusion injury

目的观察缝隙连接激动剂抗心律失常肽(AAP10)对兔心肌缺血再灌注心律失常的影响并探讨其作用机制。方法将40只日本大耳白兔随机分为缺血再灌注(IR)组、AAP10低浓度组、AAP10中浓度组、AAP10高浓度组,每组10只。缺血再灌注组灌流正常台氏液稳定后停灌40min再灌。AAP10组灌流正常台氏液+AAP10(100nmol/L、500nmol/L、1000nmol/L)稳定后停灌40min再灌。采用程序刺激诱发室性心动过速(VT)。观察刺激反应间期(SRI)、动作电位形态和时程、VT的发生率、IR后心肌恢复时间。实验结束后测量左室楔形心肌块质量、左室质量、全心质量。结果①各组左室楔形心肌块质量与左室质量之比、全心质量差异无统计学意义(P>0.05)。②AAP10组用药前后其心内膜及心外膜的动作电位形态和时程均无明显变化(P均>0.05)。③不同浓度AAP10组,SRI较IR组均明显缩短(P均<0.01)。④缺血再灌注组、AAP10低、中、高浓度组室性心动过速的发生率分别为100%(10/10)、50%(5/10)、20%(2/10)和1%(1/10),P<0.05。⑤不同AAP10浓度组缺血再灌注后心肌恢复时间均较IR组明显缩短(P均<0.01)。结论AAP10可以在不影响动作电位形态和时程的前提下提高缝隙连接的传导速度,降低兔心肌缺血再灌注心律失常发生率,保护受损心肌,有望成为治疗心律失常的一个新方法。

Aim： To explore the effects of antiarrhythmic peptide （AAP10）, a kind of gap junctional activator, on ventrieuiar arrhythmia in rabbits with ischemia-reperfusion injury. Methods：A total of 40 rabbits were randomly divided into four groups （n = 10） ： IR group, AAP10 （ 100 nmoL/L, 500 nmoL/L, 1000 nmoL/L）groups. An arterially perfused rabbit left ventricular wedge preparation was made. IR group was perfused with Tyrode＇s solution, and AAP10 group was perfused Tyrode＇s solution ＋ AAP10 （100 nmol/L, 500 nmol/L, 1000 nmol/L）. The wedge was subjected to a 40 mln coronary artery occlusion and 1 h reperfusion. Transmembrane action potentials were recorded. The stimulus-response-interval （SRI）, myocardial recovery time, and the incidence of ventricular arrhythmia （VT） were observed as well. At last, the weight of left ventricular wedge preparation, left ventricle and whole heart were measured. Results： The high incidence of VT was observed in IR group. In comparison, SRI and myocardial recovery time were shortened （P 〈0. 01 ） and the incidence of VT was decreased in AAP10 groups. The action potential morphology and duration did not altered significantly. Conclusion： AAP10 can increase gap junctional inter-cellular conductance and decrease the incidence of VT without affecting the action potential morphology and duration.