Hashimoto K, Mitsuhashi H, Akiyama K, Komori S
Jpn Circ J. 1987 Feb;51(2):196-202. doi: 10.1253/jcj.51.196.
Locally-induced digitalis arrhythmia was produced to study whether antiarrhythmic drugs suppress arrhythmia by directly acting on the abnormal impulse generation or by suppressing Na channels of normal myocardium to make it unresponsive to abnormal impulses. Dogs were thoractomized and the anterior descending artery (ADA) was isolated and autoperfused with arterial blood from the carotid artery. Forty micrograms and an additional 10 micrograms every 20 min of ouabain was injected directly into the ADA produced ventricular tachycardia originating from the digitalis intoxication. Locally injected class 1 antiarrhythmic drugs, including tetrodotoxin, were effective in suppressing this arrhythmia. However, when intravenously applied lidocaine was prevented from reaching the ADA area, lidocaine was not effective in suppressing this arrhythmia. We conclude that class 1 drugs produce antiarrhythmic effect by directly suppressing the digitalis toxicated area, not by suppressing the normal myocardium.
通过产生局部诱导的洋地黄性心律失常来研究抗心律失常药物是通过直接作用于异常冲动的产生来抑制心律失常,还是通过抑制正常心肌的钠通道使其对异常冲动无反应。对狗进行开胸手术,分离出前降动脉(ADA),并用来自颈动脉的动脉血进行自身灌注。将40微克哇巴因每隔20分钟额外注射10微克直接注入ADA,引发由洋地黄中毒引起的室性心动过速。局部注射包括河豚毒素在内的1类抗心律失常药物可有效抑制这种心律失常。然而,当静脉应用的利多卡因无法到达ADA区域时,利多卡因对抑制这种心律失常无效。我们得出结论,1类药物通过直接抑制洋地黄中毒区域产生抗心律失常作用,而非通过抑制正常心肌。