摘要目的 研究胺碘酮与抗心律失常肽合用抗心律失常的效果.方法 日本长耳兔200只,随机分为假手术组20只(A组)和结扎冠状动脉的心肌梗死(心梗)模型组180只.术后8 周末,再将存活的124只心梗模型兔随机分为对照组31只(B组)、胺碘酮组31只(C组)、抗心律失常肽(AAP10)组31只(D组)、胺碘酮+AAP10组31只(E组).第9周开始给A、B及D组兔口饲生理盐水2 ml、1次/d,给C、E组兔口饲含胺碘酮的生理盐水2 ml、1次/d,胺碘酮用量100 mg·kg-1·d-1.12周末,A、B、C、D、E组各存活20、24、26、25、27只.查超声心动图,麻醉后取左室心肌块动脉插管灌流,A、B及C组灌流台氏液,D、E组灌流加入500 nmol/L AAP10的台氏液,程序刺激同时记录容积心电图及QT、QRS、ERP、Tp-e及室性心律失常诱发率,计算Tp-e/QT.灌流完成后取心肌组织,利用Western blot和免疫荧光技术检测缝隙连接蛋白(Cx)43.组间计数资料统计学分析采用bonferroni方法校正的卡方检验或精确检验,以P＜0.05为差异有统计学意义.组间计量资料统计分析采用完全随机设计资料的方差分析;另B、C、D、E组间计量资料采用析因设计的方差分析,以评价两种药物之间的交互作用,以P＜0.05为差异有统计学意义.结果 A、B、C、D、E组心律失常诱发率分别为0、62.5%、26.9%、40.0%、22.2%,E组较B组诱发率减小.B组较A组Tp-e/QT增大,E组较B组Tp-e/QT减小.B组较A组Cx43表达明显减少.C、E组较B组Cx43表达增加,差异有统计学意义.结论 陈旧性心梗兔离体心肌块模型可用于室性心律失常的研究.胺碘酮慢性应用能上调心梗兔Cx43,与AAP10合用上调心梗兔Cx43作用加强,并进一步减小Tp-e/QT,抗心律失常作用进一步加强.

abstractsObjective The aim of this study is to observe the effect of combined amiodarone and antiarrhythmic peptide (AAP10) use on the incidence of induced ventricular arrhythmias in healed myocardial infarction (MI) rabbits. Methods Twenty Japanese rabbits underwent thoracotomy without coronary artery ligation( Sham, group A) ,the middle left circumflex branch were ligated to induce MI in 180 Japanese rabbits. Eight weeks after operation, 124 rabbits survived MI operation and were divided into four groups: control group (group B, n =31 ), amiodarone group (group C, n =31 ), AAP10 group (group D,n =31 ) and amiodarone plus AAP10 group ( group E, n =31 ). The A and B and D groups were treated with saline 2 ml/d, the C and E groups were treated with 2 ml saline containing amiodarone 100 mg· kg-1·d-1. All rabbits were examined by echocardiogram at 12 weeks after operation, then anesthetized by sodium barbital, the left wedge ventricular preparations were cannulated and artery perfused by Tyrode's solution in vitro in the absence (Group A, B and C) and presence of AAP10 (500 nmol/L, Group D and E). The volume electrocardiogram, QT Interval, QRS interval, effective refractory period (ERP), the T-peak to Tend interval ( Tp-e ), and ventricular tachycardia episodes induced by programmed stimulation were recorded.The Tp-e/QT ratio was calculated. After perfusion, gap junctions protein connexin 43 (Cx43) expression was detected by Western blot and immunofluorescence. Results The incidence of induced ventricular tachycardia episodes of group A, B, C, D, E was 0, 62. 5%, 26. 9%, 40.0%, 22. 2% respectively. The incidence of induced ventricular tachycardia episodes of group E was less than group B. The Tp-e/QT ratio in group B, C, D were greater than in group A. The Tp-e/QT ratio of group E was less than group B. The myocardial Cx43 in the group B was down-regulated and disorganized compared to group A, up-regulated in group C and E compared to group B, up-regulated in group E compared to group D. The Cx43 in the heart of group D and E were well organized than in group B and C. Conclusions The artery perfused rabbits wedge preparations with healed myocardial infarction with high incidence of induced ventricular tachycardia episodes are good platform for ventricular arrhythmias research. Combined amiodarone and AAP10 use could decrease the Tp-e/QT ratio and the incidence of induced ventricular tachycardia episodes. Amiodarone and AAP10have synergistic effects on upregulating Cx43 and preventing ventricular arrhythmias in this rabbit model of healed myocardial infarction.