Effects of quinidine on repolarization in canine epicardium, midmyocardium, and endocardium: II. In vivo study.

Effects of quinidine on repolarization in canine epicardium, midmyocardium, and endocardium: II. In vivo study.
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奎尼丁对犬心外膜、心肌中层和心内膜复极的影响:II.

DOI:
10.1161/01.cir.96.11.4019
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发表时间:
1997
期刊:
影响因子:
37.8
通讯作者:
Rosen,MR
Rosen,MR
中科院分区:
医学1区
文献类型:
--
作者:
Anyukhovsky,EP;Sosunov,EA;Feinmark,SJ;Rosen,MR

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背景在相关文章中,我们报道了奎尼丁对体外培养的犬左心室表面(心外膜和心内膜)细胞和中层心肌细胞(M细胞)动作电位时程的显著差异。本文考虑了先前研究提出的两个问题:(1)体外复杂的奎尼丁效应是否反映在其对心脏的原位作用中?(2)奎尼丁对心电图QT间期影响的细胞决定因素是什么?方法与结果我们用插入电极和表面电极测量了在房室传导阻滞和右室起搏条件下,犬左室心外膜、心内膜和中层心肌(距心外膜3、5和9 mm)的双极电信号的激活-恢复间期(ARI)。奎尼丁持续输注,血药浓度由30min时的1.6±0.1μg/m L升至180 m in时的7.6±0.7μg/L。在注射奎尼丁前和注射奎尼丁期间,在300~1500ms的周期长度(CLS)下,跨室壁无ARI梯度。在CL为300ms时,奎尼丁的治疗浓度延长了ARIS和QT间期。在1500ms的CL下,低浓度奎尼丁可显著延长ARIS。随着奎尼丁浓度的增加,这种作用减弱并消失。结论奎尼丁引起的复极延长在心肌各层中是一致的,并遵循在体外观察到的M细胞的模式。治疗浓度的奎尼丁能够在快速心率下延长复极的能力有助于其抗心律失常的效果。
BackgroundIn the companion article, we report a significant difference in quinidine effects on the action potential duration between surface (epicardial and endocardial) cells and midmyocardial cells (M cells) of canine left ventricle in vitro. This article considers two questions raised by the previous study: (1) Are the complex quinidine effects in vitro reflected in its actions on the heart in situ? (2) What are the cellular determinants of quinidine effects on QT interval in ECG?Methods and ResultsWe used plunge and surface electrodes to measure activation-recovery intervals (ARIs) of bipolar electrograms obtained from epicardium, endocardium, and midmyocardium (3, 5, and 9 mm from epicardium) of canine left ventricle in conditions of AV block and right ventricular pacing. Quinidine was infused continuously; its plasma level increased from 1.6±0.1 μg/mL at 30 minutes to 7.6±0.7 μg/mL at 180 minutes. At cycle lengths (CLs) from 300 to 1500 ms, there was no ARI gradient across the ventricular wall before and during quinidine infusion. At a CL of 300 ms, therapeutic concentrations of quinidine prolonged ARIs and QT intervals. At a CL of 1500 ms, ARIs were significantly prolonged at low quinidine concentrations. With an increase of quinidine concentration, this effect subsided and disappeared.ConclusionsIn situ, quinidine-induced prolongation of repolarization is uniform in all myocardial layers and follows the pattern observed in M cells in vitro. The ability of quinidine in therapeutic concentrations to prolong repolarization at rapid heart rates can contribute to its antiarrhythmic efficacy.
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