Do antiarrhythmic drugs act on the site of abnormal impulse generation or act on the normal myocardium?

Abstract

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.