心脏晚Na电流对APD频率适应性及药物致心律失常的影响  

Effect of cardiac I_(Na-L) on APD accommodation and drug induced arrhythmia

作　　者：杨琳[1] 薛小临[1] 李丽[1] 孙红梅[1] 张虹[2] 

机构地区：[1]西安交通大学医学院第一附属医院心内科,西安710061 [2]西安交通大学电气工程学院,西安710049

出　　处：《中国临床药理学杂志》2011年第6期472-475,共4页The Chinese Journal of Clinical Pharmacology

基　　金：国家自然科学基金资助项目(3087065930971221)

摘　　要：多种处方药物可作用于心脏IKr通道,延缓心脏兴奋的复极化过程,并呈现"反向频率依赖性"特征,即心率减慢时,药物延长复极的作用更为明显,从而增加致心律失常的危险性。心脏晚Na电流(INa-L)是动作电位复极化的重要电流,通道失活具有电压和时间依赖性,并且失活后恢复过程缓慢,因此其参与药物作用的"反向频率依赖性"调节,并加强IKr阻断药物的致心律失常作用。INa-L增大是多种心脏病(如3型长QT综合征(LQT3)、心室肥厚、心力衰竭)的共同表现,导致原本比较安全的药物,致心律失常危险性增大。INa-L阻断药(雷诺嗪)可减小心室复极异质性,对伴有INa-L增大的心脏病患者,其对降低药物致TdP发生危险性有一定的临床意义。A number of prescription drugs could block rapidly activating delayed rectifier potassium current（IKr） channel and delay the process of cardiac repolarization.IKr blockers exhibit reverse use dependence,which means that drug-induced repolarization prolongation is more prominent during bradycardia and increase the risk of arrhythmogenesis.Cardiac late sodium current（INa-L） is another important current responsible for repolarization.The inactivation of INa-L channel is voltage and time dependent and has very slow inactivation as well as recovery kinetics.So,INa-L contributes to reverse use dependence and enhance the proarrhythmic effect of IKr blockades.INa-L increases during long QT syndrome type 3（LQT3）,cardiac hypertrophy,and heart failure,and unmasks the proarrhythmic effect of safer drugs,eg,amiodarone.Ranolazine,an INa-L blocker,could decrease ventricular heterogeneity of repolarization.It is helpful for the patients with enhanced INa-L to attenuate TdP genesis as taking IKr blockade.

关 键 词：晚Na电流 反向频率依赖性 药物致心律失常 

分 类 号：R541.7[医药卫生—心血管疾病] R972.2[医药卫生—内科学]