胺碘酮对陈旧心肌梗死兔心缝隙连接重构及复极离散度的影响

Effects of Amiodarone on Cardiac Gap Junction Remodeling and Dispersion of Repolarization in Rabbits with Healed Myocardial Infarction

目的建立心肌梗死兔左室心肌块室性心律失常模型,研究胺碘酮对陈旧心肌梗死兔心缝隙连接重构及复极离散度的影响。方法日本长耳白兔110只,随机分为假手术组(A组)20只,心肌梗死组(B组)45只,心肌梗死胺碘酮干预组(C组)45只。B组及C组采取开胸结扎冠脉左室支的方法制作心肌梗死模型。术后9周开始,A组及B组口饲生理盐水2 mL,1次/d,C组口饲含胺碘酮的生理盐水2 mL,1次/d,胺碘酮用量100 mg/(kg.d)。术后12周末A组存活20只,B组存活24只,C组存活26只,行超声心动图检查后,取左室心肌块离体灌流,同时记录容积心电图及QT间期(QT)、T波波峰至T波终末间期(Tp-e)、有效不应期(ERP)、室性心律失常诱发率等电生理参数。灌流完成后分别取左室心肌组织,利用Western blot和免疫荧光方法检测缝隙连接蛋白Cx43。结果超声检测显示B组、C组较之A组左室射血分数减低。B组较之A组Tp-e增大,Tp-e/QT增大,室性心律失常诱发率明显增加,心肌Cx43重构明显。而C组与B组相比,QT延长同时Tp-e不增加,Tp-e/QT缩小,室性心律失常诱发率降低,心肌Cx43重构减轻。结论陈旧心肌梗死兔离体心肌块模型可用于室性心律失常的研究。胺碘酮可以改善陈旧心肌梗死兔心缝隙连接重构,缩小Tp-e/QT,减少室性心律失常诱发率。改善缝隙连接重构是胺碘酮不增加心室肌复极离散度的原因之一。

Objective To establish a model system to study ventricular arrhythmias after healed myocardial infarction and testify the antiarrhytbmic effect of amiodarone and its effects on cardiac gap junctions and transmural dispersion of repolarization（TDR）. Methods The sham operated rabbits（group A, n = 20）, rabbits with healed myocardial infarction 12 weeks after ligation by middle piece of left circumflex branch（group B, n = 24）and myocardial infarction rabbits treated with oral amiodarone 100 mg/（kg.d） for 4 weeks（group C,n = 26）were examined by echocardiogram. Then the left wedge ventricular preparation was cannulated and artery perfused by Tyrode＇s solution in vitro. The volume electrocardiogram, the QT interval, the Tp-e interval（T peak to T-end）and ventricular tachycardia episodes induced by programmed stimulation were recorded. The Tp-e/QT ratio was calculated. After perfusion, Western blot and immunofluorescence were used to detect gap junctions protein eonnexin 43 （Cx43）. Results The left ventricular ejection fraction in groups B or C was less than in group A. The incidence of ventricular tachycardia episodes in group B was increased as compared with group A,and that in group C was decreased as compared with group B. The Tp-e/QT ratio in group B was higher than group A,and that in group C was lower than group B. The Cx43 expression in the heart of group B was down-regulated as compared with group A,which was reversed by amiodarone in rabbits with myocardial infarction. Conclusion The artery-perfused rabbits wedge preparations with healed myocardial infarction which demonstrated increased Tp-e/QT ratio and a high incidence of induced ventricular tachyeardia episodes could be a good platform for research on ventrieular arrhythmias. Amiodarone decreased the Tp-e/QT ratio and the incidence of induced ventricular tachy cardia episodes. Up regulating Cx43 by amiodarone partly explained its effect on transmural dispersion of repolarization.