Antiarrhythmic activity of flestolol, a novel ultra-short-acting beta-adrenoceptor antagonist, in the dog.
The antiarrhythmic activity of flestolol, an ultra-short acting beta-adrenergic blocker lacking appreciable local anesthetic activity, was examined in several different canine ventricular arrhythmia models. Flestolol, at steady state infusions of 1-1,000 micrograms/kg per min, was generally ineffective in reversing either ouabain-induced or delayed ischemia-induced (24 h Harris dog) ventricular tachycardia. However, flestolol (1, 10 and 100 micrograms/kg per min) produced a dose-dependent decrease in l-norepinephrine (5 micrograms/kg i.v.)-induced ventricular tachycardia in the 5-6 day old Harris dog; the effect of 100 micrograms/kg per min flestolol, 94% suppression of norepinephrine-induced ventricular tachycardia, was completely reversed 60 min after termination of flestolol infusion. In pentobarbital-anesthetized open-chest dogs with pretreatment heart rates greater than or equal to 145 beats/min, flestolol (10 micrograms/kg per min) reduced the incidence of ventricular fibrillation resulting from abrupt coronary artery occlusion compared to placebo-treated controls (15% or 2/13 vs. 70% or 7/10, respectively). These results demonstrate that flestolol has an antiarrhythmic profile consistent with its lack of local anesthetic activity and its ultra-short duration of beta-blockade.
D000319:Adrenergic beta-Antagonists / Q000494:pharmacology*; D000818:Animals; D000889:Anti-Arrhythmia Agents; D001145:Arrhythmias, Cardiac / Q000139:chemically induced; D001794:Blood Pressure / Q000187:drug effects; D002395:Catecholamines; D003331:Coronary Vessels / Q000502:physiology; D004285:Dogs; D005260:Female; D005464:Fluorobenzenes; D006339:Heart Rate / Q000187:drug effects; D008297:Male; D009638:Norepinephrine / Q000494:pharmacology; D010042:Ouabain; D011412:Propanolamines / Q000494:pharmacology*
D000319:Adrenergic beta-Antagonists; D000889:Anti-Arrhythmia Agents; D002395:Catecholamines; D005464:Fluorobenzenes; D011412:Propanolamines; D010042:Ouabain; C047847:flestolol; D009638:Norepinephrine