Roden D M
Vanderbilt University, Division of Clinical Pharmacology, Nashville, TN 37232-6602.
Eur Heart J. 1993 Nov;14 Suppl H:56-61. doi: 10.1093/eurheartj/14.suppl_h.56.
Common clinical features in drug-induced torsade de pointes include hypokalemia and cycle-length prolongation just prior to initiation of the arrhythmia. In canine Purkinje fibres, drugs known to be associated with torsade de pointes, such as quinidine, sotalol or N-acetylprocainamide, consistently produce early after-depolarizations (EADs) and triggered activity at slow drive rates; for quinidine, these abnormalities are exaggerated by low extracellular potassium. Triggered activity can be abolished in vitro in two ways. First, action-potential shortening with abolition of EADs can be accomplished by increasing stimulation rates, beta-stimulation and action-potential shortening antiarrhythmics such as lidocaine. Second, triggered activity can be suppressed, with less prominent effects on EADs, by magnesium, alpha- and/or beta-adrenergic blockade and calcium-channel blockers. The parallels between these in vitro findings and clinical torsade de pointes suggest that EADs and triggered activity play a role in the genesis of the clinical arrhythmia. Further research directed at determining the mechanisms underlying the cellular abnormalities and their propagation to the whole heart should yield information that will increase the safety of antiarrhythmic therapy.
药物诱导的尖端扭转型室速的常见临床特征包括低钾血症以及心律失常发作前的周期长度延长。在犬浦肯野纤维中，已知与尖端扭转型室速相关的药物，如奎尼丁、索他洛尔或N - 乙酰普鲁卡因胺，在缓慢驱动频率下持续产生早期后除极（EADs）和触发活动；对于奎尼丁，低细胞外钾会加剧这些异常。触发活动在体外可以通过两种方式消除。首先，通过增加刺激频率、β刺激以及使用如利多卡因等缩短动作电位的抗心律失常药物，可以实现动作电位缩短并消除EADs。其次，镁、α和/或β肾上腺素能阻断以及钙通道阻滞剂可以抑制触发活动，对EADs的影响较小。这些体外研究结果与临床尖端扭转型室速之间的相似性表明，EADs和触发活动在临床心律失常的发生中起作用。针对确定细胞异常及其向全心传播的潜在机制的进一步研究，应该能够提供增加抗心律失常治疗安全性的信息。
