奎尼丁
复极
内科学
医学
QT间期
钠通道
心室颤动
心脏病学
耐火期
钠
电生理学
化学
有机化学
作者
Lin Wu,Donglin Guo,Hong Li,James Hackett,Gan‐Xin Yan,Zhen Jiao,Charles Antzelevitch,John C. Shryock,Luiz Belardinelli
出处
期刊:Heart Rhythm
[Elsevier]
日期:2008-12-01
卷期号:5 (12): 1726-1734
被引量:81
标识
DOI:10.1016/j.hrthm.2008.09.008
摘要
Quinidine is used to treat atrial fibrillation and ventricular arrhythmias. However, at low concentrations, it can induce torsade de pointes (TdP).The purpose of this study was to examine the role of late sodium current (I(Na)) as a modulator of the arrhythmogenicity of quinidine in female rabbit isolated hearts and cardiomyocytes.Epicardial and endocardial monophasic action potentials (MAPs), ECG signals, and ion channel currents were measured. The sea anemone toxin ATX-II was used to increase late I(Na).Quinidine had concentration-dependent and often biphasic effects on measures of arrhythmogenicity. Quinidine increased the duration of epicardial MAP (MAPD(90)), QT interval, transmural dispersion of repolarization (TDR), and ventricular effective refractory period. Beat-to-beat variability of MAPD(90) (BVR), the interval from peak to end of the T wave (Tpeak-Tend) and index of Tpeak-Tend/QT interval were greater at 0.1 to 3 micromol/L than at 10-30 micromol/L quinidine. In the presence of 1 nmol/L ATX-II, quinidine caused significantly greater concentration-dependent and biphasic changes of Tpeak-Tend, TDR, BVR, and index of Tpeak-Tend/QT interval. Quinidine (1 micromol/L) induced TdP in 2 and 13 of 14 hearts in the absence and presence of ATX-II, respectively. Increases of BVR, index of Tpeak-Tend/QT interval, and Tpeak-Tend were associated with quinidine-induced TdP. Quinidine inhibited I(Kr), peak I(Na), and late I(Na) with IC(50)s of 4.5 +/- 0.3 micromol/L, 11.0 +/- 0.7 micromol/L, and 12.0 +/- 0.7 micromol/L.Quinidine had biphasic proarrhythmic effects in the presence of ATX-II, suggesting that late I(Na) is a modulator of the arrhythmogenicity of quinidine. Enhancement of late I(Na) increased proarrhythmia caused by low but not high concentrations of quinidine.
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