Katritsis D, Camm A J
Department of Cardiological Sciences, St George's Hospital Medical School, London, U.K.
Eur Heart J. 1993 Nov;14 Suppl H:93-9. doi: 10.1093/eurheartj/14.suppl_h.93.
Several new antiarrhythmic compounds with pure class III activity are currently under development and seem to possess considerable antiarrhythmic potential. The primary electrophysiological action of class III agents is selective prolongation of repolarization without conduction slowing. This effect is usually mediated by block of one or more potassium currents which results in prolongation of the action-potential duration and refractoriness in both atrial and ventricular myocardium. The magnitude of increases in effective refractory period decreases as the heart rate is increased, i.e. these drugs display 'reverse use-dependence'. Initial animal and clinical studies have shown that class III agents are effective against re-entrant supraventricular and ventricular arrhythmias without having any important negative inotropic effect in the compromised ventricle. Animal studies have also suggested that these drugs may be useful in suppressing postinfarction arrhythmias and preventing arrhythmic sudden death. However, concerns have been raised by reports of substantial proarrhythmic tendency associated with these drugs, mainly in the form of torsade de pointes. Careful clinical evaluation is required to establish the clinical benefits of these potentially promising new compounds.
目前有几种具有纯III类活性的新型抗心律失常化合物正在研发中，似乎具有相当大的抗心律失常潜力。III类药物的主要电生理作用是选择性延长复极化而不伴有传导减慢。这种效应通常由一种或多种钾电流的阻断介导，这会导致心房和心室心肌动作电位持续时间和不应期延长。有效不应期的增加幅度随着心率的增加而减小，即这些药物表现出“反向频率依赖性”。最初的动物和临床研究表明，III类药物对折返性室上性和室性心律失常有效，且对受损心室没有任何重要的负性肌力作用。动物研究还表明，这些药物可能有助于抑制梗死后心律失常并预防心律失常性猝死。然而，有报道称这些药物存在明显的促心律失常倾向，主要表现为尖端扭转型室速，这引发了人们的担忧。需要进行仔细的临床评估，以确定这些潜在有前景的新化合物的临床益处。
