Reevaluation of digoxin-encainide interactions using an animal model

The effects of intravenous encainide on digoxin-induced atrial ectopic tachycardia (AET) were investigated in the rat using 3-channel simultaneous limb-lead electrocardiography. Pentobarbital-anesthetized (35 mg/kg, intraperitoneal) adult male rats were given digoxin subcutaneously, 30 mg/kg. After onset of AET, rats received either saline (0.5 ml/kg) or encainide; 0.25, 0.5, 1.0, or 2.0 mg/kg intravenously in repeated doses at 15-min intervals. At all doses, encainide converted digoxin-induced AET to ventricular arrhythmias, prolonged recovery time, and increased mortality in comparison to saline-treated animals. An additional group of anesthetized rats was not given digoxin. These animals received encainide (2.0 mg/kg, intravenously) in repeated doses at 15-min interval and developed dose-related increase in the P-R interval only. Blood samples were obtained by cardiac puncture from 12 additional anesthetized, digoxin-treated rats 5 min after the fourth intravenous dose of saline (0.5 ml/kg, n = 6) or encainide (1.0 mg/kg, n = 6). Serum was prepared and analyzed by affinity column-mediated immunoassay. Digoxin levels were the same in both groups. These results suggest that encainide may exacerbate digoxin-induced arrhythmias (proarrhythmic effect) in this species. In view of our findings of digoxin-encainide interactions in the rat, we recommend caution if these drugs are coadministered in humans.