Frommeyer Gerrit, Puckhaber Dirk, Ellermann Christian, Dechering Dirk G, Kochhäuser Simon, Leitz Patrick, Reinke Florian, Eckardt Lars
Division of Electrophysiology, Department of Cardiovascular Medicine, University of Münster, Münster, Germany.
Division of Electrophysiology, Department of Cardiovascular Medicine, University of Münster, Münster, Germany.
Int J Cardiol. 2017 Feb 1;228:74-79. doi: 10.1016/j.ijcard.2016.11.024. Epub 2016 Nov 7.
A post hoc analysis of the PALLAS trial suggested possible interactions of dronedarone and digitalis glycosides. The aim of the present study was to compare the effects dronedarone or amiodarone in combination with digitalis glycosides.
Eleven female rabbits underwent chronic oral treatment with amiodarone (50mg/kg/d for 6weeks). Ten rabbits were treated with dronedarone (50mg/kg/d for 6weeks). Ten rabbits were used as controls. Hearts were isolated and Langendorff-perfused. Monophasic action potentials and ECG showed a moderate prolongation of QT interval and action potential duration (APD). Both drugs also increased effective refractory period. Additional application of ouabain (0.2μM) resulted in a significant decrease of QT interval, APD, and ERP in all groups. Ventricular arrhythmias were induced by programmed ventricular stimulation and aggressive burst stimulation. Reproducible occurrence was defined as occurrence of at least 3 episodes. Under baseline conditions in control hearts, ventricular fibrillation (VF) was inducible in 1 of 10 hearts (7 episodes). After the application of 0.2μM ouabain, 4 of 10 control hearts were inducible (24 episodes). One of 10 dronedarone-pretreated hearts (3 episodes) and 2 of 11 amiodarone-pretreated hearts (6 episodes) showed VF before ouabain infusion. After the application of 0.2μM ouabain, 7 of 10 dronedarone-pretreated hearts were inducible (73 episodes). By contrast, only 4 of 11 amiodarone-pretreated hearts (13 episodes) showed VF.
In the present study, additional treatment with ouabain resulted in an increased ventricular vulnerability in al study groups. Of note, chronically dronedarone-pretreated hearts were significantly more vulnerable than amiodarone-pretreated hearts.
对PALLAS试验的事后分析表明决奈达隆与洋地黄苷可能存在相互作用。本研究的目的是比较决奈达隆或胺碘酮与洋地黄苷联合使用的效果。
11只雌性兔子接受了胺碘酮的慢性口服治疗（50mg/kg/天，持续6周）。10只兔子接受了决奈达隆治疗（50mg/kg/天，持续6周）。10只兔子作为对照。分离心脏并进行Langendorff灌注。单相动作电位和心电图显示QT间期和动作电位持续时间（APD）有适度延长。两种药物还增加了有效不应期。额外应用哇巴因（0.2μM）导致所有组的QT间期、APD和ERP显著降低。通过程序性心室刺激和激进的猝发刺激诱发室性心律失常。可重复发生定义为至少发生3次发作。在对照心脏的基线条件下，10只心脏中有1只（7次发作）可诱发心室颤动（VF）。应用0.2μM哇巴因后，10只对照心脏中有4只（24次发作）可诱发。在输注哇巴因前，10只接受决奈达隆预处理的心脏中有1只（3次发作）和11只接受胺碘酮预处理的心脏中有2只（6次发作）出现VF。应用0.2μM哇巴因后，10只接受决奈达隆预处理的心脏中有7只（73次发作）可诱发。相比之下，11只接受胺碘酮预处理的心脏中只有4只（13次发作）出现VF。
在本研究中，额外使用哇巴因治疗导致所有研究组的心室易损性增加。值得注意的是，长期接受决奈达隆预处理的心脏比接受胺碘酮预处理的心脏更易损。
