title: Alpha-adrenoceptor stimulation and blockade modulates cesium-induced early afterdepolarizations and ventricular tachyarrhythmias in dogs.
abstract: In 84 open-chest dogs, we studied the effects on early afterdepolarizations (EADs) and ventricular tachyarrhythmias (VTs) induced by cesium chloride (168 mg/kg i.v.) of alpha-adrenoceptor stimulation with phenylephrine (100 micrograms plus 0.25 microgram/kg/min i.v.) and with left ansa subclavia stimulation (LAS; 2 Hz, 4 msec, 2 mA) after propranolol (0.5 mg/kg) administration. We also studied the effects of alpha-adrenoceptor blockade with phentolamine (3 mg/kg), prazosin (25-500 micrograms/kg), yohimbine (10-500 micrograms/kg), WB 4101 (2 mg/kg), and benoxathian (2 mg/kg) during decentralized LAS. EAD amplitude, presented as a percentage of monophasic action potential amplitude, was recorded simultaneously with contact electrodes from the right and left ventricular endocardium. Phenylephrine and LAS plus propranolol increased EAD amplitude (31.5 +/- 8.8% to 47.8 +/- 9.7% and 34.8 +/- 4.1% to 46.1 +/- 6.4%, respectively) and the prevalence of VT (from three to nine of 11 dogs and from the three to five of six dogs, respectively). Prazosin produced a dose-response decrease in EAD amplitude and reduced the prevalence of VT. Yohimbine did not alter the amplitude of EADs or the prevalence of VT. WB 4101 and phentolamine reduced the amplitude of EADs produced by cesium and LAS (from 44.3 +/- 10.2% to 32.6 +/- 9.4% and from 39.8 +/- 6.9% to 30.3 +/- 6.3%, respectively) and the prevalence of VT (from eight to one of 10 dogs and from 13 to 5 of 20 dogs, respectively). Benoxathian did not alter significantly the amplitude of EADs (41.6 +/- 11.4% to 37.5 +/- 9.4%) or the prevalence of VT (from six to five of 10 dogs).(ABSTRACT TRUNCATED AT 250 WORDS)
authors.affiliation: Krannert Institute of Cardiology, Department of Medicine, Indiana University School of Medicine, Indianapolis 46202.
authors.forename: J
authors.initials: J
authors.lastname: Ben-David
authors.forename: D P
authors.initials: DP
authors.lastname: Zipes
mesh_terms: D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology*; D000818:Animals; D002304:Cardiac Pacing, Artificial; D002586:Cesium / Q000494:pharmacology*; D004285:Dogs; D004594:Electrophysiology; D005728:Ganglia, Sympathetic / Q000502:physiology; D006321:Heart / Q000502:physiology*; D008133:Long QT Syndrome / Q000503:physiopathology; D010656:Phenylephrine / Q000494:pharmacology; D011433:Propranolol / Q000494:pharmacology; D011942:Receptors, Adrenergic, alpha / Q000502:physiology*; D013617:Tachycardia, Supraventricular / Q000503:physiopathology*
chemical_list: D000317:Adrenergic alpha-Antagonists; D011942:Receptors, Adrenergic, alpha; D002586:Cesium; D010656:Phenylephrine; D011433:Propranolol