Grant A O
Duke University Medical Center, Durham, North Carolina 27710, USA.
Am J Cardiol. 1998 Oct 16;82(8A):43N-49N. doi: 10.1016/s0002-9149(98)00585-2.
Drugs remain the mainstay of treatment of patients with atrial fibrillation (AF). An understanding of the mechanisms of AF and of atrioventricular (AV) conduction provides a basis for the understanding of the mechanisms of antiarrhythmic drug action. Although ectopic activity from a focus may initiate AF, re-entry is the usual mechanism of maintenance. In its classical form, reentry takes the form of circus movements around fixed anatomic structures. However, leading circle and anisotropic variants of reentry may arise as a result of functional variations of refractoriness or anistropic conduction. Electrical remodeling during AF favors its persistence. Reentry may be prevented by prolongation of the refractory period. Class III antiarrhythmic drugs prolong refractoriness by blockade of outward potassium currents. Class I drugs prolong refractoriness by delaying the recovery of of the sodium current. Many class I drugs also have potassium channel-blocking action. In AF the rate of conduction of rapid impulses to the ventricle is controlled by conduction over the AV node. Blockade of the L-type calcium channels, activation of the muscarinic and adenosine A1 receptors, or beta-adrenergic blockade will slow conduction over the AV node. The adverse cardiovascular effects of drugs used to treat AF can be predicted on the basis of their mechanisms of action. The current focus of drug development is on specific potassium channel blockers.
药物仍然是心房颤动（AF）患者治疗的主要手段。了解房颤机制和房室（AV）传导可为理解抗心律失常药物的作用机制提供基础。虽然来自一个病灶的异位活动可能引发房颤，但折返是维持房颤的常见机制。在其经典形式中，折返表现为围绕固定解剖结构的环形运动。然而，由于不应期或各向异性传导的功能变化，可能会出现折返的主导环和各向异性变体。房颤期间的电重构有利于其持续存在。延长不应期可预防折返。Ⅲ类抗心律失常药物通过阻断外向钾电流来延长不应期。Ⅰ类药物通过延迟钠电流的恢复来延长不应期。许多Ⅰ类药物也具有钾通道阻滞作用。在房颤中，快速冲动向心室的传导速率由房室结的传导控制。阻断L型钙通道、激活毒蕈碱和腺苷A1受体或β肾上腺素能阻断将减慢房室结的传导。用于治疗房颤的药物的不良心血管效应可根据其作用机制进行预测。目前药物研发的重点是特异性钾通道阻滞剂。
