title: Protective actions of carbocromene against amitriptyline-induced cardiotoxicity in anesthetized rats.
abstract: This study was designed to analyze the effects of carbocromene on circulatory and electrophysiologic failure in rats anesthetized with urethane. Amitriptyline was infused at 0.4 mg/kg/min (n = 12) until death of the animals at 30 +/- 6.7 min due to vascular collapse. Following initial heart rate increase and QRS prolongation, this was characterized by progressive hypotension, bradycardia, intraventricular conduction delay, S-T segment elevation and A-V block. In the initial 31 rats, carbocromene was administered i.v. with 4 mg/kg followed in two groups by 40 (n = 13) and 80 micrograms/kg/min (n = 18) i.v., respectively. The drug was effective in protecting the animals against the acute cardiovascular failure induced by amitriptyline. The preservation was associated with a diminution of the hypotension, negative chronotropic actions, S-T segment elevation and the incidence of A-V block produced by amitriptyline. Survival time of the rats increased to 46 +/- 5.3 min (p less than 0.05 vs. amitriptyline controls) and 63 +/- 6.5 min (p less than 0.01) with infusion of 40 and 80 micrograms/kg/min carbocromene, respectively. These results suggest that carbocromene is an effective treatment of amitriptyline-induced cardiotoxicity by massive overdose with beneficial effects largely due to hemodynamic and metabolic oxygen-sparing impact on the heart. Membrane stabilizing antiarrhythmic carbocromene effects may be contributory factors in its protective value in the treatment of acute amitriptyline poisoning.
mesh_terms: D000639:Amitriptyline / Q000037:antagonists & inhibitors* / Q000633:toxicity; D000758:Anesthesia; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002866:Chromonar / Q000494:pharmacology*; D003374:Coumarins / Q000494:pharmacology*; D004562:Electrocardiography; D006329:Heart Conduction System / Q000187:drug effects; D006331:Heart Diseases / Q000139:chemically induced*; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects; D008297:Male; D051381:Rats; D012121:Respiration, Artificial
chemical_list: D003374:Coumarins; D000639:Amitriptyline; D002866:Chromonar