Acute dronedarone is inferior to amiodarone in terminating and preventing atrial fibrillation in canine atria
Acute dronedarone is inferior to amiodarone in terminating and preventing atrial fibrillation in canine atria
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DOI：
10.1016/j.hrthm.2010.05.019
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发表时间：
2010-09-01
期刊：
影响因子：
5.5
通讯作者：
Antzelevitch, Charles
中科院分区：
文献类型：
--
作者：
Burashnikov, Alexander;Belardinelli, Luiz;Antzelevitch, Charles
Dronectin是由美国批准的。S.美国食品药品监督管理局（FDA）将其用于治疗房颤（AF）患者，作为胺碘酮的安全替代品。有没有完整的长度发表的报告，描述了急性决奈达隆使用对AF的有效性在实验或临床study.Objective本研究的目的是确定急性决奈达隆和胺碘酮对电生理参数的影响，和他们的抗AF疗效在犬离体动脉灌注右atria.METHODS跨膜动作电位和伪心电图记录。乙酰胆碱结果胺碘酮引起的AF在（1）动作电位时程上的变化比决奈达隆明显（Δ APD 90，+51 +/- 17 ms vs. 4 +/- 6 ms，P > .01），（2）有效不应期（Δ ERP，+84 +/- 23 ms vs. 18 +/- 9 ms，P < .001），（3）舒张期兴奋阈值（Delta DTE，+0.32 +/- 0.11 mA vs. 0.03 +/- 0.02 mA，P < .001）和（4）V（最大值）（Δ V（最大值），-43 +/-14%对-11 +/-4%，P < .01，n = 5至6;均在10 μ M下记录，循环长度= 500 ms）。在10/10个单独暴露于ACh的心房中诱导了持续性AF;随后添加决奈达隆或胺碘酮分别终止了1/7个和4/5个心房的AF。结论在房颤犬模型中，急性决奈达隆的电生理作用和抗房颤疗效明显弱于胺碘酮，急性决奈达隆预防乙酰胆碱介导的房颤和终止犬右心房持续性房颤的疗效相对较差。我们的数据表明，对于AF的急性心脏复律或预防AF复发，急性决奈达隆是胺碘酮的不良替代品。
BACKGROUND Dronedarone is approved by the U. S. Food and Drug Administration for the treatment of patients with atrial fibrillation (AF) as a safe alternative to amiodarone. There are no full-length published reports describing the effectiveness of acute dronedarone use against AF in experimental or clinical studies.OBJECTIVE The purpose of this study was to determine the effect of acute dronedarone and amiodarone on electrophysiological parameters, and their anti-AF efficacy in canine isolated arterially perfused right atria.METHODS Transmembrane action potentials and pseudoelectrocardiograms were recorded. Acetylcholine (ACh, 1.0 mu M) was used to induce persistent AF.RESULTS Amiodarone-induced changes were much more pronounced than those of dronedarone on (1) action potential duration (Delta APD90, +51 +/- 17 ms vs. 4 +/- 6 ms, P > .01), (2) effective refractory period (Delta ERP, +84 +/- 23 ms vs. 18 +/- 9 ms, P < .001), (3) diastolic threshold of excitation (Delta DTE, +0.32 +/- 0.11 mA vs. 0.03 +/- 0.02 mA, P < .001), and (4) V(max) (Delta V(max), -43 +/- 14% vs. -11 +/- 4%, P < .01, n = 5 to 6; all recorded at 10 mu M, cycle length = 500 ms). Persistent AF was induced in 10 of 10 atria exposed to ACh alone; subsequent addition of dronedarone or amiodarone terminated AF in 1 of 7 and 4 of 5 atria, respectively. Persistent ACh-mediated AF was induced in 5 of 6 and 0 of 5 atria pretreated with dronedarone and amiodarone, respectively.CONCLUSION The electrophysiological effects and anti-AF efficacy of acute dronedarone are much weaker than those of amiodarone in a canine model of AF. The efficacy of acute dronedarone to prevent induction of acetylcholine-mediated AF as well as to terminate persistent AF in canine right atria is relatively poor. Our data suggest that acute dronedarone is a poor substitute for amiodarone for acute cardioversion of AF or prevention of AF recurrence.