Treatment of haemodynamic and electrocardiographic side-effects resulting from imipramine toxicity in rats and dogs

This study was designed to analyze the effects of carbocromene and dipyridamole on the haemodynamic and electrocardiographic side-effects resulting from imipramine infusion in anaesthetised rats and dogs. Imipramine was infused at 1 mg/kg/min until cardiac failure and vascular collapse terminated the experiment at 21 +/- 2.3 min in rats and at 29.5 +/- 2.1 min in dogs. This was characterized by hypotension, bradycardia, intraventricular conduction delay, cardiac tachyarrhythmia and A-V block. Carbocromene (4 mg/kg i.v., followed by 80 micrograms/kg/min) protected the animals against heart failure. This was associated with delayed hypotension and negative inotropy, and lower incidence of heart block. Survival time increased to 37 +/- 1.5 min (P less than 0.05), and 54.2 +/- 2.6 min (P less than 0.02) in rats and dogs, respectively. Dipyridamole (0.5 mg/kg i.v., followed by 80 micrograms/kg/min) failed to decrease imipramine toxicity as judged by the haemodynamic and electrocardiographic parameters and did not alter survival time of imipramine controls. These results suggest that carbocromene is an effective treatment for imipramine-induced cardiovascular collapse and cardiac arrhythmias, the beneficial effects being largely due to metabolic and membrane stabilizing effects. Carbocromene has both therapeutic and prophylactic value and appears to be superior to dipyridamole therapy.