Maruyama T, Richardson L C, Sun W, McCarthy J J, Gettes L S
Department of Medicine, School of Medicine, University of North Carolina, Chapel Hill 27599-7075, USA.
Heart Vessels. 1995;10(2):78-86. doi: 10.1007/BF01744498.
Amiodarone has potent and complex antiarrhythmic effects associated with a rare incidence of proarrhythmia. For a comprehensive understanding of its antiarrhythmic mechanisms in the same preparations, amiodarone (50 microM) was employed as it would be in the clinical setting and applied to guinea pig papillary muscles impaled by microelectrodes, paced at different rates, and superfused with various concentrations of potassium ([K]e). Amiodarone exerted complex actions, as follows: (1) The maximum rate of rise (Vmax) of the fast action potential (i.e., [K]e = 5.4-9.0 mM) as well as that of the slow action potential (i.e., [K]e = 15.0 mM in the presence of 1.0 microM isoproterenol) was suppressed in a rate-dependent manner. (2) Amiodarone exhibited a rate- and [K]e-dependent increase in the ratio of effective refractory period vs action potential duration at 90% repolarization (ERP/APD90), disclosing post-repolarization refractoriness. (3) Amiodarone had no effect on passive cable factors, such as threshold current and tissue resistance, during propagation. These versatile electrophysiological effects of amiodarone may contribute to its unique antiarrhythmic effects, as well as the low incidence of proarrhythmia with this drug.
胺碘酮具有强大而复杂的抗心律失常作用，致心律失常的发生率很低。为全面了解其在相同制剂中的抗心律失常机制，采用了临床应用时的胺碘酮浓度（50微摩尔），并将其应用于用微电极刺入的豚鼠乳头肌，以不同速率起搏，并用不同浓度的钾（[K]e）进行灌流。胺碘酮产生了如下复杂作用：（1）快动作电位（即[K]e = 5.4 - 9.0毫摩尔）以及慢动作电位（即在1.0微摩尔异丙肾上腺素存在下[K]e = 15.0毫摩尔）的最大上升速率（Vmax）以速率依赖性方式受到抑制。（2）胺碘酮在90%复极化时有效不应期与动作电位时程的比值（ERP/APD90）呈现出速率和[K]e依赖性增加，揭示了复极化后不应期。（3）胺碘酮在传播过程中对被动电缆因素，如阈电流和组织电阻没有影响。胺碘酮这些多样的电生理效应可能有助于其独特的抗心律失常作用，以及该药物致心律失常的低发生率。
