Antiarrhythmic effect of disulfiram in various cardiotoxic models.
Disulfiram has been shown to decrease the incidence of arrhythmias in rabbits exposed to trichloroethylene. In this study additional cardiotoxic models were used to evaluate disulfiram's antiarrhythmogenicity. Disulfiram (7.5 mg/kg, i.v.) significantly decreased the time spent in arrhythmia compared to control rabbits, 120-180 s following intravenous administration of 4 mg/kg barium chloride. This was very similar to the effect of quinidine sulfate (10 mg/kg, i.v.) used as a positive control. In ouabain-induced arrhythmias, disulfiram treatment (400 mg/kg, i.p.) did not significantly alter the arrhythmogenic or lethal doses of a ouabain infusion. Quinidine, however, significantly increased the arrhythmogenic dose 86% and the lethal dose 44% compared to control. In vitro studies demonstrated that disulfiram (1 X 10(-4) and 3 X 10(-4) M) significantly depressed the myocardial contractility of rat ventricular strips compared to polyethylene glycol 400 controls.
D000818:Animals; D000889:Anti-Arrhythmia Agents; D004195:Disease Models, Animal; D004221:Disulfiram / Q000494:pharmacology*; D006331:Heart Diseases / Q000139:chemically induced / Q000503:physiopathology*; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects; D010042:Ouabain / Q000494:pharmacology; D011802:Quinidine / Q000494:pharmacology; D011817:Rabbits; D051381:Rats; D011919:Rats, Inbred Strains
D000889:Anti-Arrhythmia Agents; D010042:Ouabain; D011802:Quinidine; D004221:Disulfiram