Synergistic effect of the combination of ranolazine and dronedarone to suppress atrial fibrillation.
Synergistic effect of the combination of ranolazine and dronedarone to suppress atrial fibrillation.
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DOI：
10.1016/j.jacc.2010.08.600
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发表时间：
2010-10-05
影响因子：
24
通讯作者：
Antzelevitch, Charles
中科院分区：
文献类型：
--
作者：
Burashnikov, Alexander;Sicouri, Serge;Di Diego, Jose M.;Belardinelli, Luiz;Antzelevitch, Charles
本研究旨在评价决奈达隆和雷诺嗪联合治疗抑制房颤（AF）的有效性。安全有效的房颤药物治疗仍然是最大的未满足医疗需求之一。在犬离体冠状动脉灌注右心房和左心房以及左心室制备物以及肺静脉制备物中评价了决奈达隆（10 μmol/l）和相对低浓度雷诺嗪（5 μmol/l）单独和联合给药的电生理学效应。雷诺嗪导致动作电位时程中度心房选择性延长和钠通道介导参数的心房选择性抑制，包括动作电位上升的最大速率，导致心房特异性复极后不应性的发展。在心房和心室准备中，Dronectin引起的电生理参数变化很小或没有变化。决奈达隆和雷诺嗪联合给药对两个心室的动作电位时程几乎没有影响，但可诱导钠通道介导参数（动作电位上行程的最大上升速率、舒张期兴奋阈值和允许1：1反应的最短周期长度）的有效使用依赖性心房选择性抑制和相当大的复极后不应性。另外，决奈达隆或低浓度雷诺嗪分别在17%和29%的制剂中预防了AF的诱导。联合使用时，2种药物抑制AF并触发活动，并在10种制剂中的9种（90%）中阻止AF的诱导。当单独使用时，低浓度雷诺嗪和决奈达隆产生相对较弱的电生理学效应和较弱的AF抑制，但当联合使用时产生有效的协同效应，导致钠通道依赖性参数的心房选择性抑制和AF的有效抑制（J Am科尔Cardiol 2010;56：1216-24）。
The aim of this study was to evaluate the effectiveness of a combination of dronedarone and ranolazine in suppression of atrial fibrillation (AF). Safe and effective pharmacological management of AF remains one of the greatest unmet medical needs. The electrophysiological effects of dronedarone (10 μmol/l) and a relatively low concentration of ranolazine (5 μmol/l) separately and in combination were evaluated in canine isolated coronary-perfused right and left atrial and left ventricular preparations as well as in pulmonary vein preparations. Ranolazine caused moderate atrial-selective prolongation of action potential duration and atrial-selective depression of sodium channel–mediated parameters, including maximal rate of rise of the action potential upstroke, leading to the development of atrial-specific post-repolarization refractoriness. Dronedarone caused little or no change in electrophysiological parameters in both atrial and ventricular preparations. The combination of drone-darone and ranolazine caused little change in action potential duration in either chamber but induced potent use-dependent atrial-selective depression of the sodium channel–mediated parameters (maximal rate of rise of the action potential upstroke, diastolic threshold of excitation, and the shortest cycle length permitting a 1:1 response) and considerable post-repolarization refractoriness. Separately, dronedarone or a low concentration of ranolazine prevented the induction of AF in 17% and 29% of preparations, respectively. In combination, the 2 drugs suppressed AF and triggered activity and prevented the induction of AF in 9 of 10 preparations (90%). Low concentrations of ranolazine and dronedarone produce relatively weak electrophysiological effects and weak suppression of AF when used separately but when combined exert potent synergistic effects, resulting in atrial-selective depression of sodium channel–dependent parameters and effective suppression of AF. (J Am Coll Cardiol 2010;56:1216–24)
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影响因子：
2.7
作者：
Sicouri S;Belardinelli L;Carlsson L;Antzelevitch C
通讯作者：
Antzelevitch C
影响因子：
158.5
作者：
Hohnloser, Stefan H.;Crijns, Harry J. G. M.;Connolly, Stuart J.
通讯作者：
Connolly, Stuart J.
影响因子：
3
作者：
Gautier, P;Guillemare, E;Nisato, D
通讯作者：
Nisato, D
影响因子：
5.5
作者：
Patterson, E;Po, SS;Lazzara, R
通讯作者：
Lazzara, R
影响因子：
37.8
作者：
Sun, W;Sarma, JSM;Singh, BN
通讯作者：
Singh, BN