Torsadegenic Action of the Antipsychotic Drug Sulpiride Assessed Using In Vivo Canine Models
Torsadegenic Action of the Antipsychotic Drug Sulpiride Assessed Using In Vivo Canine Models
复制标题
使用体内犬模型评估抗精神病药物舒必利的扭转性扭转作用
DOI：
10.1097/00005344-200208000-00009
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发表时间：
2002
影响因子：
3
通讯作者：
K. Hashimoto
中科院分区：
文献类型：
--
作者：
A. Sugiyama;Y. Satoh;H. Shiina;S. Takeda;K. Hashimoto
1例患者在开始舒必利治疗后出现QT延长和晕厥。本实验旨在阐明舒必利给药、QT延长和尖端扭矩发作之间的因果联系。采用氟烷麻醉犬和慢性房室传导阻滞犬两种体内模型。在氟烷麻醉动物(n=6)中，静脉注射舒必利(2 mg/kg和20 mg/kg)可降低总外周阻力，增加心率、心输出量和心室收缩能力。在高剂量给药后不久，这些影响就出现了短暂的减弱。大剂量给药后左室前负荷和除极无明显变化，但复极和有效不应期明显延长。复极化的变化幅度大于不应期，表明复极化的最后阶段(电易损期)延长。慢性房室传导阻滞动物(n=4)口服舒必利60 mg/kg和120 mg/kg后出现尖端扭体反应，QT明显延长。提示舒必利致心律失常的机制可能与QT延长和终末复极时相改变而增加交感神经张力有关。因此，应谨慎使用舒必利，这些患者有血浆浓度升高的风险，且先前存在QT延长的易感性。
A patient had QT prolongation and syncope after starting sulpiride therapy. The present experiments were performed to clarify the causal link among the sulpiride administration, QT prolongation, and the onset of torsade de pointes. Two in vivo models were used: halothane-anesthetized dogs and chronic atrioventricular (AV) block dogs. In the halothane-anesthetized animals (n = 6), sulpiride (2 and 20 mg/kg intravenously) decreased total peripheral resistance and increased heart rate, cardiac output, and ventricular contractility concomitantly. A transient attenuation of these effects occurred soon after the high-dose administration. No significant change was detected in left ventricle preload and depolarization, but repolarization and effective refractory period were significantly prolonged after high-dose administration. The extent of changes was greater in repolarization than in refractoriness, indicating prolongation of the final repolarization phase (electrically vulnerable period). In the chronic AV block animals (n = 4), onset of torsades de pointes with marked QT prolongation was demonstrated after the administration of 60 and 120 mg/kg orally of sulpiride. These results suggest that the QT prolongation and the change in the final repolarization phase with increased sympathetic tone may be the mechanisms responsible for the arrhythmogenic effect of sulpiride. Thus, caution should be paid with the use of sulpiride in patients at risk for elevated plasma concentrations and having preexisting susceptibility to QT prolongation.
心动过缓期间的快速心率可延长犬的心室不应期并促进铯诱发室性心动过速。
影响因子：
37.8
作者：
Satoh,T;Zipes,DP
通讯作者：
Zipes,DP