卡维地洛与维司力农:心力衰竭中新的抗心律失常途径(英文)

卡维地洛和维司力农是近年来受到瞩目的慢性充血性心力衰竭治疗药。电生理学研究表明这些药物可适度延长心室肌的动作电位时程(APD)而无明显的逆频度依存性,然而其产生这一作用的离子机制是不同的。卡维地洛可阻断L-型钙电流(I_(Ca)),一过性外向钾电流(I_(to))以及延迟整流钾电流(I_K),特别是其快速激活成份(I_(Kr))。维司力农是一个选择性的I_K阻滞剂,具有独特的药物-通道相互作用。根据维司力农对I_K的电位与时间依存性抑制作用,该药被认为在I_K(主要是I_(Kr))通道处于激活状态时与其结合,而在通道关闭时则发生解离。这些电生理学特性将为器质性心脏病患者理想的抗心律失常药的开发提供新的途径。

Carvedilol and vesnarinone: new antiarrhythmic approach in heart failu re therapy

Carvedilol and vesnarinone are drugs attracting re-cent interest in the treatment of chronic heart failure. Electrophysiologic studies have revealed that these drugs cause a moderate prolongation of action potential duratior (APD) of ventricular muscles with minimal "reverse fre-quency-dependence" through different ionic mechanisms. Carvedilol blocks L-type Ca2 cunrent (Ica), transiem outward K current (Ito), and delayed rectifier K cur-rent (Ik ) preferentially for the rapidly activating compo-nent (Ikr). Vesnarinone is a selective blocker of IK with a unique drug-channel interaction. From the volt-age- and time-dependence of IK inhibition, vesnarinone is considered to bind the IK(mainly Ikr) channel during the activated state and unbind during the closed state. These electropharmacologic profiles provide a new approach for the development of an ideal antiarrhythmic drugs in pa-tients with structural heart diseases.