Vaughan Williams E M
Eur Heart J. 1985 Nov;6 Suppl D:145-9. doi: 10.1093/eurheartj/6.suppl_d.145.
Depolarization of cardiac muscle is achieved by 'fast inward current' through channels which are inactivated within about 1 ms. When the cells are repolarized the process of inactivation of fast channels is rapidly reversed. The class 1 anti-arrhythmic drugs delay the disappearance of inactivation until long after repolarization is complete. In theory, it should be possible to produce a similar extension of refractory period by delaying the repolarization itself. Quinidine and disopyramide caused minor delays of repolarization, but both were primarily class 1 agents, and in addition had undesirable anticholinergic activity. Amiodarone, already in use for many years as an antianginal drug, prolonged action potential duration (APD) and was shown to have an anti-arrhythmic action in rabbits, dogs and man. Although prolongation of APD lengthens QT, a long QT may be caused by phenomena other than prolonged APD, such as heterogeneity of sympathetic drive. Association of long QT with arrhythmia does not, therefore, invalidate the principle that homogeneously prolonged APD should be anti-arrhythmic. In practice, amiodarone, bretylium, sotalol, thyroidectomy, and long-term beta-blockade prolong APD, and are associated with low incidence of arrhythmia. Many mechanisms controlling cardiac repolarization have been proposed, but how repolarization is delayed by individual agents is not fully elucidated.
心肌的去极化是通过“快速内向电流”经通道实现的，这些通道在约1毫秒内失活。当细胞复极化时，快速通道的失活过程迅速逆转。1类抗心律失常药物会延迟失活的消失，直到复极化完成很久之后。理论上，通过延迟复极化本身应该有可能产生类似的不应期延长。奎尼丁和丙吡胺会引起轻微的复极化延迟，但两者主要都是1类药物，此外还具有不良的抗胆碱能活性。多年来一直作为抗心绞痛药物使用的胺碘酮，延长了动作电位持续时间（APD），并在兔、犬和人类中显示出抗心律失常作用。虽然APD延长会使QT间期延长，但QT间期延长可能由除APD延长之外的其他现象引起，如交感神经驱动的异质性。因此，长QT与心律失常的关联并不否定均匀延长APD应具有抗心律失常作用这一原则。在实践中，胺碘酮、溴苄铵、索他洛尔、甲状腺切除术和长期β受体阻滞剂会延长APD，并与心律失常的低发生率相关。已经提出了许多控制心脏复极化的机制，但个别药物如何延迟复极化尚未完全阐明。
