Clinical electrophysiology of flestolol, a potent ultra short-acting beta blocker

Abstract

We measured the electrophysiologic effects of flestolol, and ultra short-acting beta blocker, in 15 patients at two infusion rates: a 45 μg/kg loading dose followed by a 5 μg/kg/min infusion and a 60 μg/kg loading dose followed by a 10 μg/kg/min infusion. Electrophysiologic measurements were made after 15 minutes at each infusion rate (plasma concentrations 46 ± 11 and 94 ± 23 ng/ml). Flestolol produced dose-dependent effects on the sinus node, the atrioventricular (AV) node, and right ventricular refractoriness, whereas atrial refractoriness and infranodal conduction were unchanged. At the 10 μg/kg/min dose, flestolol prolonged sinus cycle length by a mean of 20% ( p = 0.0001), corrected sinus node recovery time by 42% ( p = 0.02), AH interval by 21% ( p = 0.0001), AV node effective refractory period by 28%, AV node Wenckebach cycle length by 30% (0.0001), and right ventricular effective refractory period by 5% ( p = 0.03). A significant concentration-effect relationship ( p ≤ 0.03) was present for all variables which had significant dose-effect relationships. No patient developed hypotension, bradyarrhythmias, or other toxicity. Sinus cycle length decreased linearly with time in the post infusion period ( r = 0.99); by 30 minutes post infusion, measured electrophysiologic variables had returned to control values and flestolol plasma concentration had decreased to 4 ± 2 ng/ml. Flestolol's electrophysiologic effects are similar to those of other beta blockers. In doses up to 10 μg/kg/min, it is safe in selected patients, has rapid onset and offset of action, and does not cause acute rebound.