Saikawa T, Nagamoto Y, Arita M
Jpn Heart J. 1977 Mar;18(2):235-45. doi: 10.1536/ihj.18.235.
The effect of diltiazem hydrochloride (CRD-401), a coronary vasodilator, was investigated in isolated perfused canine ventricular muscles and Purkinje fibers using microelectrodes. The drug at a concentration of 1 microng/ml lowered the level of action potential plateau and shortened the duration in both ventricular and Purkinje fibers without change in maximum rate of rise (Vmax) or resting potential. Contractile tension of ventricular muscle was markedly decreased with shortening of plateau. With higher drug concentrations (5 microng/ml), Vmax in both ventricular muscle and Purkinje fiber decreased about 20% without change in resting potential, and the effect on repolarization became more marked. The drug blocked spontaneous firing which appeared in depolarized Purkinje fibers and abolished the automaticity elicited in electrically depolarized ventricular muscles. Input resistance of ventricular muscle, measured by small, hyperpolarizing short pulses, was not changed appreciably by the drug; suggesting no change in potassium conductance. These results suggest that the drug is a slow channel inhibitor, and its clinical implication is discussed in terms of antiarrhythmic activity.
使用微电极，在离体灌流的犬心室肌和浦肯野纤维中研究了冠状动脉扩张剂盐酸地尔硫䓬（CRD - 401）的作用。浓度为1微克/毫升的该药物降低了心室肌和浦肯野纤维动作电位平台期水平并缩短了动作电位持续时间，而最大上升速率（Vmax）或静息电位无变化。随着平台期缩短，心室肌的收缩张力显著降低。在更高药物浓度（5微克/毫升）时，心室肌和浦肯野纤维的Vmax均降低约20%，静息电位无变化，且对复极化的影响更显著。该药物阻断了去极化浦肯野纤维中出现的自发放电，并消除了电去极化心室肌中引发的自律性。通过小的超极化短脉冲测量的心室肌输入电阻，未因该药物而有明显变化；提示钾电导无变化。这些结果表明该药物是一种慢通道抑制剂，并根据抗心律失常活性讨论了其临床意义。
