DESIPRAMINE TOXICITY AND ITS TREATMENT

Effect of a continuous intravenous infusion of desipramine (0.5 mg/kg/min) on blood pressure, myocardial contractile force and electrocardiogram (ECG) was investigated in anesthetized mongrel dogs. Following an initial sympathomimetic effect, desipramine produced a depression of contractile force and a lowering of blood pressure. In most experiments, prolongation of the P-R interval and QRS duration, with no other appreciable change in the ECG pattern, were seen in doses as high as 25 mg/kg. In a few experiments, however, ventricular ectopic beats and multifocal ventricular tachycardia were observed during desipramine infusion. Withdrawal of desipramine infusion at a time when the contractile force was depressed by 66% or 100% of control values did not reverse the myocardial depressant effects so that complete cardiac arrest was produced as the end result. Administration of epinephrine following desipramine-induced myocardial depression had only a transient myocardial stimulant effect, and reversal of myocardial depression could not be obtained in either of the two experimental groups. On the other hand, ouabain (20 μg/kg) injected after 66% depression of contractile force by desipramine restored the contractility to the pre-desipramine levels. In experiments where 100% depression of contractile force was obtained with desipramine, a combined administration of epinephrine (1 μg/kg) followed by ouabain (20 μg/kg) was necessary to obtain an immediate and sustained increase in the myocardial contractility. © 1969.