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Efficacy of disopyramide in comparison with verapamil and propranolol in the prevention of acetylcholine-induced atrial fibrillation in the dog.

The efficacy of verapamil and propranolol was studied in comparison with disopyramide on the atrial fibrillation experimentally induced in the dog heart in situ by electrical stimulation combined with intra-aortic injection of acetylcholine (ACh). After reducing the amplitude and duration of the monophasic action potential (MAP) and the duration of the effective refractory period (ERP) of the atrial contractile fibres, ACh lowered the fibrillation threshold (FT), and, when fibrillation had been elicited, it accelerated the fibrillation rate (FR). Verapamil and propranolol failed to prevent atrial fibrillation: they did not counteract any of the alterations in the electrophysiological properties of the atrial contractile fibres due to ACh. In contrast, disopyramide, at doses within the therapeutic range, prevented fibrillation. The fibrillation threshold, which fell from 50 mA to 1 mA in the presence of ACh, was restored to control values by disopyramide. Disopyramide also antagonized the reduction in amplitude of MAP caused by ACh before the triggering of fibrillation and the reductions by ACh of the durations of MAP and ERP. Disopyramide first slowed FR, in association with an increase in amplitude of fibrillation waves and a tendency to synchronous activity, and ultimately terminated the fibrillation.