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Antiarrhythmic effect of disulfiram in various cardiotoxic models
Abstract:
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.
Insights
Disulfiram shows antiarrhythmic effects in barium chloride-induced arrhythmias but not ouabain-induced ones. Further research is needed to understand its cardiac effects.
Area of Science:
- Pharmacology
- Cardiology
- Toxicology
Background:
- Disulfiram (DSF) has demonstrated antiarrhythmic properties in specific models.
- Previous research indicated DSF reduces trichloroethylene-induced arrhythmias in rabbits.
Purpose of the Study:
- To evaluate the antiarrhythmogenic potential of disulfiram in additional cardiotoxic models.
- To compare disulfiram's effects with quinidine sulfate, a known antiarrhythmic drug.
Main Methods:
- In vivo studies using barium chloride and ouabain to induce arrhythmias in rabbits.
- In vitro assessment of disulfiram's effect on rat ventricular myocardial contractility.
- Administration of disulfiram and quinidine sulfate at specified dosages and routes.
Main Results:
- Disulfiram significantly reduced arrhythmia duration in barium chloride-induced models, similar to quinidine.
- Disulfiram did not alter arrhythmogenic or lethal doses in ouabain-induced arrhythmias, unlike quinidine.
- In vitro, disulfiram depressed myocardial contractility in rat ventricular strips.
Conclusions:
- Disulfiram exhibits antiarrhythmic effects in certain models but not others.
- The drug's impact on myocardial contractility suggests potential proarrhythmic or cardiotoxic effects at higher concentrations.
- Further investigation is warranted to elucidate disulfiram's complex cardiovascular profile.