ELECTROPHYSIOLOGIC EFFECTS OF BRETYLIUM TOSYLATE ON THE HEART

¹ Departments of Medicine and Physiology, Duke University Medical Center, Durham, North Carolina

In eight dogs, chronic recording electrodes were implanted over the sinoatrial node, bundle of His and right bundle branch. Pacing electrodes were implanted on the right atrium and ventricle. One to four weeks after this surgery, the effects of bretylium tosylate (10 mg/kg i.v.) on electrophysiologic properties of the heart were assessed in the awake animals. Bretylium produced an average decrease of sinus rate of 24% (132-100/min). When atrial rate was controlled by pacing, conduction time across the atrioventricular node was prolonged by 30% (97-126 msec). Conduction velocity in the right bundle branch was not altered by bretylium and total ventricular activation time was prolonged by only 3% (72-74 msec). The effective refractory periods of atrial and ventricular muscle were prolonged by 9% (163-178 msec) and 12% (156-175 msec), respectively. Bretylium had no effect on the excitability threshold of atrial or ventricular muscle. Surgical denervation of the heart failed to abolish the electrophysiologic effects of bretylium. Bretylium reduced the ventricular rate in six dogs with chronic atrioventricular block. These data indicate that the electrophysiologic effects of bretylium differ significantly from those of quinidine or lidocaine. These data also indicate that bretylium has important actions on the heart which are not dependent upon cardiac innervation or intact myocardial stores of catecholamines.

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