Canine digitalis arrhythmia as a model for detecting Na-channel blocking antiarrhythmic drugs: a comparative study using other canine arrhythmia models and the new antiarrhythmic drugs, propafenone, tocainide, and SUN 1165

Abstract

Antiarrhythmic effects of three new drugs, propafenone, tocainide, and SUN 1165, were examined using three canine ventricular arrhythmia models, i.e., digitalis, adrenaline and two-stage coronary ligation arrhythmias. The effects of procainamide, disopyramide, lidocaine, and phenytoin, class 1 antiarrhythmic drugs, on digitalis arrhythmia were also examined. The minimum effective plasma concentrations of all these drugs for each arrhythmia model were determined for a quantitative comparison. Propafenone and tocainide suppressed all the arrhythmias, while SUN 1165 suppressed digitalis and coronary ligation arrhythmias. The minimum effective plasma concentrations of propafenone for digitalis, adrenaline, 24-h coronary ligation, and 48-h coronary ligation arrhythmias were 1.8 +/- 0.7, 0.58 +/- 0.20, 3.5 +/- 0.3, and 3.6 +/- 0.9 micrograms/ml, respectively, and those of tocainide were 6.2 +/- 2.1, 23.7 +/- 9.0, 11.4 +/- 0.5, and 8.6 +/- 2.9 micrograms/ml, respectively (mean +/- standard deviation, n = 6-7). The minimum effective concentrations of SUN 1165 for digitalis, 24-h coronary ligation, and 48-h coronary ligation arrhythmias were 0.92 +/- 0.19, 2.5 +/- 0.4, and 1.2 +/- 0.4 micrograms/ml. The minimum effective concentrations for digitalis arrhythmias were 1.7 +/- 0.4 micrograms/ml for disopyramide, 10.1 +/- 2.4 micrograms/ml for procainamide, 3.5 +/- 1.6 micrograms/ml for lidocaine, and 11.3 +/- 3.0 micrograms/ml for phenytoin. Digitalis arrhythmia seems to be a useful model for detecting class 1 drugs, as it was suppressed by all the class 1 Na-channel blocking antiarrhythmic drugs, while class 2 beta adrenergic blockers and class 4 Ca-channel blockers had no effect. Also, not all the class 1 drugs suppressed coronary ligation and adrenaline arrhythmias.