The mechanism of action of the optical enantiomers of verapamil against ischaemia‐induced arrhythmias in the conscious rat
The mechanism of action of the optical enantiomers of verapamil against ischaemia‐induced arrhythmias in the conscious rat
复制标题
维拉帕米光学对映体对抗清醒大鼠缺血性心律失常的作用机制
DOI：
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发表时间：
1986
影响因子：
7.3
通讯作者：
Michael J A Walker
中科院分区：
文献类型：
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作者：
Michael J. Curtis;Michael J A Walker
1在清醒大鼠中研究了（-）-维拉帕米（0.2-6 mg kg−1）和（+）-维拉帕米（0.4-12 mg kg−1）对冠状动脉阻塞引起的心律失常的作用。2静脉注射（-）-和（+）-维拉帕米剂量依赖性地减少室性心律失常。（-）-维拉帕米的效力始终是（+）-维拉帕米的4倍。3在相同的动物中，（-）-维拉帕米对心率和血压的影响大约是（+）-维拉帕米的4倍。两种对映体均延长P-R间期，但对QRS间期无影响。4在清醒大鼠的单独组中，在左心室电刺激期间，两种对映体都不影响引起心房扑动所需的阈值电压和脉宽，或改变最大跟随频率。5在离体、起搏、Langendorff灌注的大鼠心室中，两种对映体均剂量依赖性地降低收缩力，（-）-维拉帕米的效力是（+）-维拉帕米的8-21倍;绝对和相对效力均依赖于钾浓度。6这些结果与缺血心室肌中的钙拮抗作用在急性心肌缺血期间具有抗心律失常作用的假设一致。
1 The actions of (‐)‐verapamil (0.2–6 mg kg−1) and (+)‐verapamil (0.4–12 mg kg−1) against arrhythmias induced by coronary artery occlusion were studied in conscious rats. 2 Intravenously administered (‐)‐ and (+)‐verapamil dose‐dependently reduced ventricular arrhythmias. (‐)‐Verapamil was consistently 4 times more potent than (+)‐verapamil. 3 In the same animals, (‐)‐verapamil was approximately 4 times more potent than (+)‐verapamil for effects on heart rate and blood pressure. Both enantiomers prolonged P‐R interval, but had no effect on QRS interval. 4 In separate groups of conscious rats, neither enantiomer influenced the threshold voltage and pulse width required to elicit fibrillo‐flutter, or altered the maximum following frequency, during electrical stimulation of the left ventricle. 5 In isolated, paced, Langendorff‐perfused ventricles of the rat, both enantiomers dose‐dependently reduced contractility, (‐)‐verapamil being 8–21 times more potent than (+)‐verapamil; both absolute and relative potencies were dependent on potassium concentration. 6 These results are compatible with the hypothesis that calcium antagonism in the ischaemic ventricular myocardium is antiarrhythmic during acute myocardial ischaemia.