Department of Physiology, Faculty of Medicine, Maastricht University, Universiteitssingel 50, P.O. Box 616, 6200 MD, Maastricht, The Netherlands.
Europace. 2018 Jan 1;20(1):140-148. doi: 10.1093/europace/eux025.
Besides the inhibition of the sodium inward current, vernakalant also inhibits the ultra rapid rectifier (IKur) and transient outward current (Ito). Inhibition of these currents increases contractility in canine atrial myocytes and goat atria. We investigated the effect of vernakalant on early repolarization and contractility in normal and electrically remodelled atria.
Goats were implanted a pressure catheter, piezoelectric crystals, and electrodes to obtain atrial contractility and effective refractory period (ERP). The active component in pressure distance loops was used to compute the atrial work index (AWI). Experiments were performed in normal and electrically remodelled atria at clinically relevant plasma levels of vernakalant. As a positive control, the Ito/IKur blocker AVE0118 was investigated. Monophasic action potentials were recorded in anaesthetized goats and in explanted hearts to determine changes in action potential morphology. Vernakalant did not affect atrial work loops during sinus rhythm. Likewise vernakalant did not increase atrial fractional shortening or AWI during pacing with fixed heart rate and AV-delay. In contrast, AVE0118 did increase AWI, with a positive force frequency relation. Both in normal and remodelled atria, vernakalant strongly increased ERP but did not prolong early repolarization.
In goat atria, vernakalant does not have an atrial positive inotropic effect and does not affect early repolarization. At high rates vernakalant may even have a negative inotropic effect.
除了抑制钠离子内流，维纳卡兰还抑制超快速整流电流（IKur）和瞬时外向电流（Ito）。抑制这些电流可增加犬心房肌细胞和山羊心房的收缩力。我们研究了维纳卡兰对正常和电重构心房早期复极和收缩力的影响。
山羊被植入压力导管、压电晶体和电极，以获得心房收缩力和有效不应期（ERP）。主动成分用于计算心房工作指数（AWI）。在临床相关维纳卡兰血浆水平下，在正常和电重构心房中进行实验。以 Ito/IKur 阻滞剂 AVE0118 作为阳性对照进行研究。在麻醉山羊和离体心脏中记录单相动作电位，以确定动作电位形态的变化。在窦性节律期间，维纳卡兰不影响心房工作环。同样，维纳卡兰在固定心率和 AV 延迟起搏时不增加心房分数缩短或 AWI。相比之下，AVE0118 确实增加了 AWI，具有正力频率关系。在正常和重构的心房中，维纳卡兰强烈增加 ERP，但不延长早期复极。
在山羊心房中，维纳卡兰没有心房正性肌力作用，也不影响早期复极。在高心率时，维纳卡兰甚至可能具有负性肌力作用。
