Class III antiarrhythmic action in experimental atrial fibrillation and flutter in dogs

Progress in the pharmacological treatment of atrial fibrillation and flutter has been achieved by the introduction of the class III antiarrhythmic drug amiodarone. In the present study we tested amiodarone and a new class III antiarrhythmic drug, melperone, in experimentally induced atrial fibrillation and flutter in pentobarbital-anesthetized dogs. By high-rate stimulation in the right atrium, atrial fibrillation was induced in 4, and atrial flutter in 10 out of 22 dogs. Atrial flutter rate was 496 +/- 13 min-1 (median +/- 95% confidence interval). Both drugs converted the arrhythmias at doses from 2.5 to 10 mg . kg-1 and reduced that atrial flutter rate before conversion. Average ventricular rate during arrhythmias (261 +/- 16 min-1) decreased after amiodarone, and was unchanged or, in three out of nine dogs, increased after melperone. The doses of amiodarone converting the arrhythmias increased atrial refractoriness, whereas the effects on AV nodal conduction and refractoriness were variable. The results support the concept that atrial flutter is due to circus movement where the flutter rate is dependent upon atrial refractoriness. The class III antiarrhythmic drugs amiodarone and melperone seem to be equally potent in converting atrial arrhythmias.