New antiarrhythmic drugs for atrial flutter and atrial fibrillation: a conceptual breakthrough at last?
New antiarrhythmic drugs for atrial flutter and atrial fibrillation: a conceptual breakthrough at last?
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DOI：
10.1161/circ.105.3.276
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发表时间：
2002-01
期刊：
影响因子：
37.8
通讯作者：
F. Cosío;E. Delpón
中科院分区：
文献类型：
--
作者：
F. Cosío;E. Delpón
抗心律失常药物（AAD）在临床环境中的使用仍然是一个经常令人沮丧的经验练习，尽管在了解AAD对心肌离子通道和动作电位的影响方面取得了重大进展。不仅疗效低于预期，而且在特定情况下预测AAD的抗肿瘤作用与致肿瘤作用几乎是不可能的。Vaughan威廉姆斯分类1有助于描述和分组AAD，并区分主要作用于舒张期低极化细胞（窦房和房室结）的AAD（因其对β-肾上腺素能受体和Ca 2+通道的影响）和能够减慢传导速度和/或延长工作心肌和浦肯野细胞动作电位时程的AAD。不幸的是，Vaughan威廉姆斯分类对临床医生的有用性有限，因为它提供了AAD作用、心律失常机制和治疗结果之间的不完整联系。现代心律失常学以折返概念为主导，折返是大多数临床快速性心律失常的基础。折返通常被认为是围绕中心障碍物旋转的连续激活，无论是固定的还是功能性的，并且在波长（WL）概念中已经很好地合成了维持折返所需的不应期、传导速度和回路周长之间的平衡。WL是在不应期持续时间的时间间隔内由激动前沿覆盖的回路长度（图1），显然，它必须短于总回路长度，以便留下可激动间隙;否则，激动将因遇到不应组织的屏障而熄灭。在动物实验中，起始过早冲动的WL与诱导性房性心律失常的类型有关，房颤（AF）诱导的WL最短，房扑稍长WL。2折返性心律失常的临界WL的概念导致AAD的作用应根据其影响来描述。
Antiarrhythmic drug (AAD) use in the clinical setting remains an often frustrating empirical exercise, despite significant advances in understanding the effect of AADs on myocardial ion channels and action potential. Not only is efficacy lower than desired, but prediction of antiarrhythmic versus arrhythmogenic effects of AADs in a particular case is nearly impossible. Vaughan Williams classification1 helped to describe and group AADs and to differentiate between AADs mainly acting on the low diastolic polarization cells (sinoatrial and atrioventricular nodes) for their effect on β-adrenergic receptors and Ca2+ channels and those capable of slowing conduction velocity and/or prolonging the action potential duration of the working myocardium and Purkinje cells. Unfortunately, usefulness of the Vaughan Williams classification for clinicians was limited because it provided incomplete links among AAD actions, arrhythmia mechanisms, and therapeutic results. Modern arrhythmology is dominated by the concept of reentry as the bases of most clinical tachyarrhythmias. Reentry has been conceived generally as continuous activation rotating around a central obstacle, be it fixed or functional, and the equilibrium necessary between refractory period, conduction velocity, and circuit circumference to maintain reentry has been nicely synthesized in the wavelength (WL) concept. WL is the circuit length covered by the activation front in the time lapse of refractory period duration (Figure 1) and, obviously, it must be shorter than total circuit length in order to leave an excitable gap; otherwise, activation would be extinguished by meeting a barrier of refractory tissue. In animal experiments, the WL of the initiating premature impulse was related to the type of inducible atrial arrhythmias, atrial fibrillation (AF) being induced with the shortest WL, and flutter with slightly longer WL.2 The concept of a critical WL for reentrant arrhythmias led to the suggestion that AADs effects should be described in terms of their influence …