Proarrhythmic Effects of Intravenous Quinidine, Amiodarone, d -Sotalol, and Almokalant in the Anesthetized Rabbit Model of Torsade de Pointes

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Summary:The proarrhythmic effects of four antiarrhythmic agents were examined during α 1 -adrenoceptor stimulation in chloralose-anesthetized rabbits. Each dose of almokalant (26, 88, and 260 μg/kg), d -sotalol, quinidine, or amiodarone (each 3, 10, and 30 mg/kg) was infused i.v. over 5 min and there was a 20-min interval between each infusion. d -sotalol and almokalant evoked torsade de pointes (TdP) and other arrhythmics, frequently. The incidences of TdP were 0, 50, and 40% after administering the first, second, and third doses of the nonselective I Kr inhibitor d -sotalol, respectively. Similarly, these values were 20, 40, and 33% after administering the first, second, and third doses, respectively, of the selective I Kr inhibitor almokalant. Quinidine elicited only a few arrhythmics, but not TdP. Quinidine, d -sotalol, and almokalant evoked conduction blocks in a dose-related manner (p < 0.05) and prolonged QT and QT c intervals (p < 0.05). Amiodarone neither prolonged QT and QT c nor evoked ventricular tachyarrhythmias, blocks, or other proarrhythmias. In conclusion, these results show no direct correlation between the occurrence of TdP and the infusion rate or dose of anti-arrhythmics. Furthermore, the lack of TdP with quinidine warns of false-negative results in the applied model.

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