Rote of transmural dispersion of repolarization in the genesis of drug-induced torsades de pointes
Rote of transmural dispersion of repolarization in the genesis of drug-induced torsades de pointes
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DOI：
10.1016/j.hrthm.2004.09.011
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发表时间：
2005-11-01
期刊：
影响因子：
5.5
通讯作者：
Antzelevitch, C
中科院分区：
文献类型：
--
作者：
Antzelevitch, C
尖端扭转型室性心动过速（TdP）是一种潜在的致命性心律失常，是心室肌固有电异质性放大的结果。这些异质性的存在是由于构成心室肌的三种主要细胞类型的复极时间过程的差异，从而引起跨壁电压梯度和负责ECG T波记录的复极分散。具有III类作用的抗心律失常药物和/或与长QT综合征相关的各种突变和心肌病降低了净复极化电流并放大了复极化的固有空间离散度，从而为折返的发展创造了底物。结果是QT间期延长。T波异常，多形折返性室性心动过速的发展显示TdP的特征。QT间期延长显然不是药物引起TdP的唯一决定因素。不增加跨室壁复极离散度的药物几乎或没有诱导TdP的潜力，尽管有延长QT间期的能力。另外。胺碘酮和戊巴比妥钠等药物可引起大的QT间期延长，但通过减少跨室壁复极离散度，可降低TdP的可能性。犬左心室动脉灌注楔形标本可用于探讨跨室壁复极离散度在TdP发生中的作用。这篇文章的目的是回顾最近的进展，提高了我们对这些机制的理解，特别是跨壁复极离散的作用，在药物诱导的TdP的起源，并检查这些进展如何可以引导LIS朝着更安全，更有效的药物的发展。
Torsades de pointes (TdP) is a potentially lethal arrhythmia that develops as a consequence of amplification of electrical heterogeneities intrinsic to the ventricular myocardium. These heterogeneities exist because of differences in the time Course of repolarization of the three predominant cell types that make up the ventricular myocardium, giving rise to transmural voltage gradients and a dispersion of repolarization responsible for inscription of the ECG T wave. Antiarrhythmic agents with class III actions and/or the various mutations and cardiomyopathies associated with the long QT syndrome reduce net repolarizing current and amplify the intrinsic spatial dispersion of repolarization, thus creating the substrate for the development of reentry. The result is prolongation of the QT interval. abnormal T waves, and development of polymorphic reentrant ventricular tachycardia displaying characteristics of TdP. Prolongation of the QT interval apparently is not the sole determinant of a drugs potential to cause TdP. Agents that do not increase transmural dispersion of repolarization have little or no potential to induce TdP despite any ability to prolong the QT interval. In addition. drugs Such as amiodarone and sodium pentobarbital can cause large QT prolongations but, by reducing transmural dispersion of repolarization, may reduce the likelihood of TdP. Arterially perfused wedge preparations of canine left ventricle can be used to explore the role of transmural dispersion of repolarization in the genesis of TdP. The purpose of this article is to review recent advances that have improved our understanding of these mechanisms, particularly the role of transmural dispersion of repolarization, in the genesis of drug-induced TdP and to examine how these advances can guide Lis toward the development of safer and more effective drugs.