离体心肌组织灌流在评价药源性QT间期延长中的应用及影响因素  

Application of myocardial perfusion in the assessment of drug-induced QT prolongation

作　　者：周慧[1] 汪溪洁[1] 

机构地区：[1]中国医药工业研究总院,上海医药工业研究院,国家上海新药安全评价研究中心,上海201203

出　　处：《世界临床药物》2014年第7期422-425,共4页World Clinical Drug

基　　金：国家"十二五""重大新药创制专项"课题(2012ZX09302002;上海市科委科技创新行动计划项目(13140900900)

摘　　要：QT间期延长和尖端扭转型室性心动过速是许多药物潜在的不良反应。临床前潜在致心律失常风险评估方法有助于获得更具优势的候选药物。通过离体心肌组织灌流在分离的动物心脏组织中记录动作电位是临床前药物心脏安全性评价中的重要一项。在药物早期研发过程中,将体内QT间期检测与体外电生理学研究结合,有利于监测候选药物的致心律失常风险。本文综述离体心肌组织灌流在评估候选药物潜在致心律失常风险中的应用及其影响因素。Drug-induced QT prolongation and torsades de pointes （TdPs） are potential adverse effects in a broad range of cardiovascular and non-cardiovascular drugs. Therefore, in order to acquire advancing drug candidates, we need to find more reliable preclinical assays to evaluate the potential risk on proarrhythmia of drug candidates. Recording action potential from isolated cardiac tissues with intracellular microelectrode is an important step of preclinical cardiac safety evaluation. Therefore, in the early stage of drug development, we should conduct both in vivo and in vitro assays for cardiovascular risk assessment. This article describes the myocardial perfusion applied in assessment for potential proarrhythmia risk of drug candidates and some influencing factors.

关 键 词：心肌组织灌流 QT间期延长 影响因素 

分 类 号：R965[医药卫生—药理学] R541.71[医药卫生—药学]