Imipramine cardiotoxicity: an electrocardiographic and haemodynamic study in rabbits

The purpose of the present study was to investigate the cardiotoxicity of the tricyclic antidepressant imipramine. The experiments were carried out in rabbits during continous intravenous infusion of imipramine, and electrocardiographic and haemodynamic changes were observed. The blood flows were measured using the radioactive microsphere method based upon the principles of Fick and Stewart Hamilton. It was found that the decrease in heart rate and the changes in heart rhythm were always preceded by a fall in arterial blood pressure and cardiac contractility, expressed by a fall in dp/dtmax. On the basis of the results it is concluded that a direct depressing action on the myocardium is of importance in the development of cardiac complications, although both a depressing influence on cardiac conduction, an anticholinergic effect, and an influence on adrenergic factors may also contribute. The possibility of positive correlations between the changes in plasma-imipramine concentration and the changes in the dp/dtmax and the QRS complex cannot be excluded.