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

We measured the electrophysiologic effects of flestolol, an ultra short-acting beta blocker, in 15 patients at two infusion rates: a 45 micrograms/kg loading dose followed by a 5 micrograms/kg/min infusion and a 60 micrograms/kg loading dose followed by a 10 micrograms/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 micrograms/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 less than or equal to 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 micrograms/kg/min, it is safe in selected patients, has rapid onset and offset of action, and does not cause acute rebound.