Effect of reserpine, desipramine and phenytoin on digoxin induced arrhythmias and myocardial uptake of digoxin in guinea pigs.

Abstract

Abstract: Digoxin was infused intravenously 27.5 μg/min. to guinea pigs. By means of the ECG doses of digoxin needed to cause ventricular extrasystoles (VES), ventricular fibrillation (VF), and asystole (AS) were determined in a control group without any premedication. Three groups were given a pre‐treatment with desipramine, phenytoin and reserpine. After AS digoxin concentrations in the heart muscle and in the kidneys were determined by radioimmunoassay. The concentrations of adrenaline and noradrenaline were also determined in these tissues. After reserpine and phenytoin the doses of digoxin needed to induce VF and AS were increased. Desipramine had no effect on digitalis‐induced arrhythmias. The relative uptake of digoxin in the heart muscle was decreased after all of the three premedications; there was no change in the kidney. The tissue catecholamine concentrations were decreased after reserpine and desipramine, but remained unchanged after phenytoin. The lethal dose of digoxin seemed not to correlate to the myocardial digoxin concentration after different premedications. The mechanism of the uptake in the heart muscle seemed to be different from that in the kidney. There was no correlation between the catecholamine concentration in myocardium and the ar‐rhythmogenic effect of digoxin in the different groups.