Eleclazine, a new selective cardiac late sodium current inhibitor, confers concurrent protection against autonomically induced atrial premature beats, repolarization alternans and heterogeneity, and atrial fibrillation in an intact porcine model
Eleclazine, a new selective cardiac late sodium current inhibitor, confers concurrent protection against autonomically induced atrial premature beats, repolarization alternans and heterogeneity, and atrial fibrillation in an intact porcine model
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DOI：
10.1016/j.hrthm.2016.04.015
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发表时间：
2016-08-01
期刊：
影响因子：
5.5
通讯作者：
Verrier, Richard L.
中科院分区：
文献类型：
--
作者：
Fuller, Henrique;Justo, Fernanda;Verrier, Richard L.
背景：心脏晚期钠电流（INa）与心房颤动（AF）的发生有越来越多的关系。Eledazine（以前称为GS-6615）是一种新的选择性晚期INa抑制剂，正在进行治疗心律失常的临床试验。目的研究埃雷达嗪抑制晚期INa是否对房性早搏（APBs）和房颤（AF）具有保护作用。方法给药胸麻约克猪，单独给药肾上腺素（2.0 μ g/kg，静脉注射，1分钟内给药）诱导房颤（n = 6）或联合心包内乙酰胆碱（0.5 ~ 4 mL， 12.5 mM溶液）诱导自发性房颤（n = 11）。测定哌嗪（0.3和0.9 mg/kg，静脉注射，15min以上）对apb和AF的影响。结果肾上腺素诱导的apb减少3倍(P
BACKGROUND The cardiac late sodium current (INa) has been increasingly implicated in the initiation of atrial fibrillation (AF). Eledazine (formerly known as GS-6615) is a new selective late INa inhibitor and is undergoing clinical testing for the treatment of cardiac arrhythmias.OBJECTIVE We tested whether late INa inhibition by eledazine confers protection against atrial premature beats (APBs) and AF.METHODS In dosed-chest anesthetized Yorkshire pigs, epinephrine (2.0 mu g/kg, intravenous, bolus over 1 minute) was administered alone to induce APBs (n = 6) or in combination with intrapericardial acetylcholine (0.5-4 mL of 12.5 mM solution) to induce spontaneous AF (n = 11). Effects of eledazine (0.3 and 0.9 mg/kg, intravenous, over 15 minutes) on APBs and AF were determined.RESULTS Epinephrine-induced APBs were reduced >3-fold (P