Comparison of acute electrophysiological effects of amiodarone and its metabolite desethylamiodarone in Langendorff perfused guinea pig hearts

Summary During long-term treatment with amiodarone, slowing of conduction through the atrioventricular node, a prolongation of the QT-interval, and a prolongation of the atrial and ventricular myocardial refractoriness always developed. During short-term treatment, these effects were not found, except for depression of the AV-nodal conduction. This led to the suggestion that the electrophysiological effects of amiodarone during long-term treatment might be partly the result of the accumulation of its metabolite desethylamiodarone. Therefore, we examined the electrophysiological effects of amiodarone and desethylamiodarone on conduction and refractoriness in isolated spontaneously beating guinea pig hearts perfused by the method of Langendorff. Within 1 h of perfusion, desethyl-amiodarone caused a more pronounced prolongation of the AV-nodal, His-bundle, and intraventricular conduction intervals than did amiodarone. Desethylamiodarone, but not amiodarone led to a prolongation of the QT-interval. The refractoriness of sinoatrial-, AV-nodal conduction, and of the atrial myocardium were significantly more prolonged by amiodarone than by desethylamiodarone. Both compounds showed a comparable strong rate-dependent effect on AV-nodal refractoriness. The ventricular refractoriness was similarily prolonged by either compound. These results show that for the class-III effects (i.e., prolongation of repolarization period) observed under chronic treatment of amiodarone the metabolite desethylamiodarone may be responsible. Desethylamiodarone also exerts more pronounced effects on the fast-channel-dependent parts of the conduction system than does amiodarone, a fact indicated by a higher prolongation of His-bundle and intraventricular conduction.Supported by the Austrian Research Foundation, grant P 7141 and by the Austrian Development Fund, grant 5/545 and grant Z13/7098/513     

Amiodarone pulmonary toxicity — three unusual manifestations

Amiodarone is very useful treatment for refractory arrhythmias. However, it has a wide profile of adverse effects involving a number of organ systems. Pulmonary toxicity is the most serious of these side effects and often limits its clinical use.
Three patients with unusual forms of amiodarone pulmonary toxicity are described. One had extensive unilateral alveolar disease, another pleural effusion, and in a third the pulmonary infiltrate improved with oral corticosteroids despite continuation of amiodarone therapy. Extensive unilateral alveolar disease and resolution of the pulmonary toxicity with corticosteroids despite continuing with amiodarone have not been previously reported. Pleural effusion has been noted only rarely. With the increasing use of amiodarone, pulmonary toxicity is likely to occur more frequently and it is important to be aware of its less common manifestations. (Aust NZ J Med 1992; 22: 14–18.)     

胺碘酮治疗高龄室性心律失常患者最佳剂量探讨

目的用不同剂量胺碘酮治疗70岁以上室性心律失常患者,以探讨高龄患者胺碘酮最佳剂量.方法47例患者随机分为A、B两组,A组:胺碘酮600mg/d×14d,减至400mg×14d,再减至200mg/d×14d,最后以100mg/d维持;B组:600mg/d×7d,减至400mg/d×7d,再减至200mg/d×7d,再减为100mg/d×7d,最后以50mg/d维持.结果A、B两组总有效率分别为82%、80%,两组无显著性差异,A组有6例发生不良反应,B组除2例轻度窦性心动过缓外,无其他不良反应发生.结论低剂量胺碘酮对70岁以上高龄室性心律失常患者不失为一种安全、有效的药物.     

静脉应用胺碘酮治疗器质性心脏病伴快室率心房颤动的临床疗效

目的 观察静脉应用胺碘酮治疗器质性心脏病伴快室率永久性房颤患者的临床疗效及安全性.方法 41例器质性心脏病合并房颤患者:男26例,女15例,年龄61.4±12.1(49～77岁),房颤病史半年以上,入院时心室率为151±19.3(134～179)次/分.给予静脉负荷量胺碘酮(150～300 mg)后,继之以1mg/小时静脉滴注6小时,后以0.5mg/分持续滴注42小时.结果 41例患者用药后1h、2h、6h、24h、48h心室率分划为121.3±11.7,111.5±9.3,94.7±8.7,88.4±8.6,84.2±7.3较用药前明显下降(P＜0.01),心功能明显好转,在治疗过程中,2例出现血压下降,1例出现长R-R间期,经减量给药后血压稳定,长R-R间期消失.结论 静脉应用胺碘硐治疗器质性心脏病伴快室率房颤患者有效且安全.