The non-catecholamine-mediated electrophysiological effects of intravenous bethanidine sulfate on the immature mammalian heart.
In a preliminary study, we found that bethanidine sulfate had important electrophysiologic effects on the neonatal canine heart, specifically that bethanidine increased atrial effective and functional refractory periods. Other effects (increase in heart rate blood pressure and enhanced atrioventricular conduction) were thought to be due to a release of endogenous catecholamines. To investigate the non-catecholamine-mediated effects of bethanidine, we administered 10 mg/kg i.v. bethanidine to eight neonatal puppies ages 6-14 days pretreated with 0.6 mg/kg of propranolol and compared them with a control group of six neonates that received propranolol followed by a placebo. In the bethanidine group, the mean atrial effective and functional refractory periods increased significantly from 58 to 109 ms and from 108 to 185 ms, respectively (p less than 0.0001). Bethanidine also caused a decrease in resting heart rate (from 154 beats/min postpropranolol to 144 beats/min postbethanidine, p less than 0.002). These effects were not observed in the placebo group. Wenckebach periodicity during incremental atrial pacing did not change significantly. There was a modest increase in the ventricular refractory periods following bethanidine. Thus, the direct electrophysiologic effects of bethanidine in the neonate include a significant prolongation of atrial refractoriness and a decrease in sinus node automaticity. Ventricular refractory periods, while increased, did not show the dramatic prolongation exhibited by the atrium. The atrial specificity of bethanidine is unique and may prove useful in the treatment of supraventricular arrhythmias in the neonatal period.
Villafane
J
J
Department of Pediatrics, University of Miami School of Medicine, Florida.
Xu
H
H
McCormack
J
J
Gelband
H
H
Stolfi
A
A
Pickoff
A S
AS
D000818:Animals; D000831:Animals, Newborn; D001627:Bethanidine / Q000008:administration & dosage / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D004285:Dogs; D004558:Electric Stimulation; D004594:Electrophysiology; D006321:Heart / Q000187:drug effects*; D006339:Heart Rate / Q000187:drug effects; D066298:In Vitro Techniques; D007275:Injections, Intravenous; D011433:Propranolol / Q000494:pharmacology; D012032:Refractory Period, Electrophysiological / Q000187:drug effects; D012849:Sinoatrial Node / Q000187:drug effects
D011433:Propranolol; D001627:Bethanidine