Masonic Medical Research Laboratory, Utica, New York 13501, USA.
Ann N Y Acad Sci. 2010 Feb;1188:78-86. doi: 10.1111/j.1749-6632.2009.05086.x.
Safe and effective pharmacologic management of atrial fibrillation (AF) is one of the greatest challenges facing an aging society. Currently available pharmacologic strategies for rhythm control of AF are associated with ventricular arrhythmias and in some cases multi-organ toxicity. Consequently, drug development has focused on atrial-selective agents such as IKur blockers. Recent studies suggest that IKur block alone may be ineffective for suppression of AF and may promote AF in healthy hearts. Recent experimental studies have demonstrated other important electrophysiologic differences between atrial and ventricular cells, particularly with respect to sodium channel function, and have identified sodium channel blockers that exploit these electrophysiologic distinctions. Atrial-selective sodium channel blockers, such as ranolazine and amiodarone, effectively suppress and/or prevent the induction of AF in experimental models, while producing little to no effect on ventricular myocardium. These findings suggest that atrial-selective sodium channel block may be a fruitful new strategy for the management of AF.
安全有效的心房颤动（AF）药物治疗是老龄化社会面临的最大挑战之一。目前用于 AF 节律控制的药物治疗策略与室性心律失常有关，在某些情况下还与多器官毒性有关。因此，药物研发的重点是心房选择性药物，如 IKur 阻滞剂。最近的研究表明，单独阻断 IKur 可能对抑制 AF 无效，甚至可能在健康心脏中促进 AF 的发生。最近的实验研究表明，心房细胞和心室细胞之间存在其他重要的电生理差异，特别是在钠通道功能方面，并已确定利用这些电生理差异的钠通道阻滞剂。心房选择性钠通道阻滞剂，如雷诺嗪和胺碘酮，可有效抑制和/或预防实验模型中 AF 的诱发，而对心室心肌几乎没有影响。这些发现表明，心房选择性钠通道阻断可能是 AF 管理的一个有前途的新策略。
