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.