Roden D M
Department of Medicine and Pharmacology, Vanderbilt University School of Medicine, Nashville, Tennessee 37232-6602, USA.
Am J Cardiol. 1996 Aug 29;78(4A):12-6. doi: 10.1016/s0002-9149(96)00448-1.
Drugs that prolong cardiac refractoriness exert antiarrhythmic effects, probably by reducing dispersion of refractoriness and thereby reducing the likelihood of reentrant excitation. This electrophysiologic effect can be achieved in fast-response tissues by sodium channel block or by action potential prolongation; drugs with either attribute can exert antiarrhythmic effects. However, both types of drugs can also cause proarrhythmic effects. For sodium channel blockers, proarrhythmic actions can be attributed to conduction slowing and include increased frequency of episodes of ventricular tachycardia as well as slowing of atrial flutter with 1:1 atrioventricular conduction and increases in ventricular rate. In addition, sodium channel block has been implicated as the mechanism underlying increased mortality with sodium channel blockers in the Cardiac Arrhythmia Suppression Trial (CAST); some data suggest that intercurrent ischemia increases this risk. For drugs that prolong action potentials, torsades de pointes is the most common proarrhythmic syndrome, occurring most often with underlying bradyarrhythmias and hypokalemia. The mechanism(s) underlying normal refractoriness and its modulation by antiarrhythmic drugs, as well as the mechanism(s) underlying these proarrhythmic syndromes, are discussed.
延长心脏不应期的药物发挥抗心律失常作用，可能是通过减少不应期离散度，从而降低折返激动的可能性。这种电生理效应在快反应组织中可通过钠通道阻滞或延长动作电位来实现；具有这两种特性之一的药物均可发挥抗心律失常作用。然而，这两类药物也都可引起促心律失常作用。对于钠通道阻滞剂，促心律失常作用可归因于传导减慢，包括室性心动过速发作频率增加，以及心房扑动伴1:1房室传导时减慢和心室率增加。此外，在心律失常抑制试验（CAST）中，钠通道阻滞被认为是钠通道阻滞剂导致死亡率增加的机制；一些数据表明，并发缺血会增加这种风险。对于延长动作电位的药物，尖端扭转型室性心动过速是最常见的促心律失常综合征，最常发生于潜在的缓慢性心律失常和低钾血症时。文中讨论了正常不应期的机制及其受抗心律失常药物调节的机制，以及这些促心律失常综合征的机制。
