Effects of selective KAch channel blocker NTC-801 on atreal fibrillation in a canine model of atrial tachpacing: comparison with class Ic and III drugs.
Effects of selective KAch channel blocker NTC-801 on atreal fibrillation in a canine model of atrial tachpacing: comparison with class Ic and III drugs.
复制标题
选择性 KAch 通道阻滞剂 NTC-801 对心房快速起搏犬模型中心房颤动的影响：与 Ic 类和 III 类药物的比较。
DOI：
10.1097/fjc.0000000000000065
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发表时间：
2014
期刊：
影响因子：
--
通讯作者：
Ogawa S.
中科院分区：
文献类型：
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作者：
Yamamoto W;Hashimoto N;Matsuura J;Machida T;Ogino Y;Kobayashi T;Yamanaka Y;Ishiwata N;Yamashita Y;Tanimoto K;Miyoshi S;Fukuda K;Nakaya H;Ogawa S.
本研究探讨了NTC-801，一种高选择性乙酰胆碱（ACh）受体激活钾（KACh）通道阻滞剂，对心房颤动（AF）在犬模型的电重构的影响。通过左心房（LA）快速起搏（400 bpm，3-5周）在犬中创建AF的实验基质。观察NTC-801、多非利特和氟卡尼静脉滴注15分钟对房颤诱发率、心房有效不应期（ERP）和心房传导速度的影响。同时观察NTC-801终止房颤的效果。左心房快速起搏后心房ERP缩短，AF诱发电位增加。NTC-801（0.3-3 µg· kg− 1· min− 1）延长心房ERP，与刺激频率无关，并呈剂量依赖性降低AF诱导率。多非利特（5.3 μg· kg− 1· min− 1）和氟卡尼（0.13 mg· kg− 1· min− 1）对AF诱导无显著抑制作用，对心房ERP影响极小。氟卡尼降低心房传导速度，而NTC-801和多非利特没有。NTC-801（0.1 mg/kg）将AF转为正常窦性心律。总之，NTC-801在犬左心房快速起搏AF模型中发挥了比多非利特和氟卡尼更有效的抗心律失常作用。NTC-801的抗心律失常作用可能与延长心房ERP有关，与电刺激频率无关。这些结果表明，NTC-801可以更有效地防止心房电重构的设置AF。
The present study examines the effects of NTC-801, a highly selective acetylcholine (ACh) receptor-activated potassium (K ACh) channel blocker, on atrial fibrillation (AF) in a canine model with electrical remodeling. An experimental substrate for AF was created in dogs via left atrial (LA) tachypacing (400 bpm, 3–5 weeks). NTC-801, dofetilide, and flecainide were intravenously infused for 15 minutes, and the effects on AF inducibility, atrial effective refractory period (ERP), and atrial conduction velocity were examined. The effect of NTC-801 on AF termination was also evaluated. Atrial ERP was shortened and AF inducibility was increased after LA tachypacing. NTC-801 (0.3–3 µg· kg− 1· min− 1) prolonged atrial ERP irrespective of stimulation frequency and dose-dependently decreased AF inducibility. Dofetilide (5.3 µg· kg− 1· min− 1) and flecainide (0.13 mg· kg− 1· min− 1) did not significantly inhibit AF inducibility and minimally affected atrial ERP. Flecainide decreased atrial conduction velocity, whereas NTC-801 and dofetilide did not. NTC-801 (0.1 mg/kg) converted AF to normal sinus rhythm. In summary, NTC-801 exerted more effective antiarrhythmic effects than dofetilide and flecainide in a canine LA-tachypacing AF model. The antiarrhythmic activity of NTC-801 was probably due to prolonging atrial ERP independently of stimulation frequency. These results suggest that NTC-801 could prevent AF more effectively in the setting of atrial electrical remodeling.