Varró A, Bódi I, Jednákovits A, Rabloczky G
Institute for Drug Research, Budapest, Hungary.
Arch Int Pharmacodyn Ther. 1988 Mar-Apr;292:157-65.
The frequency-dependent effect of 11 antiarrhythmic drugs on the impulse conduction time and excitability threshold was studied in isolated rabbit right ventricular muscle. Before drug application, conduction time and excitability threshold were independent of the stimulation cycle length (200-2000 msec). Quinidine, tocainide, lidocaine, disopyramide, procainamide, flecainide, lorcainide and mexiletine increased conduction time and excitability threshold in a frequency-dependent manner (use-dependency) while verapamil, clofilium and bretylium did not significantly alter conduction and excitability at any applied stimulation frequency. It was concluded that the use-dependent effect which was described earlier with most Class I antiarrhythmic drugs on the rate of rise of the action potential can be also demonstrated in extracellular electrophysiological experiments and this must be considered during routine pharmacological screenings.
在离体兔右心室肌中研究了11种抗心律失常药物对冲动传导时间和兴奋性阈值的频率依赖性效应。在应用药物之前，传导时间和兴奋性阈值与刺激周期长度（200 - 2000毫秒）无关。奎尼丁、妥卡尼、利多卡因、双异丙吡胺、普鲁卡因胺、氟卡尼、劳卡尼和美西律以频率依赖性方式（使用依赖性）增加传导时间和兴奋性阈值，而维拉帕米、氯非铵和溴苄铵在任何施加的刺激频率下均未显著改变传导和兴奋性。得出的结论是，先前大多数I类抗心律失常药物对动作电位上升速率所描述的使用依赖性效应，在细胞外电生理实验中也可以得到证实，并且在常规药理筛选过程中必须予以考虑。
