The class III antiarrhythmic effect of sotalol exerts a reverse use-dependent positive inotropic effect in the intact canine heart

OBJECTIVES We sought to study the rate related effects of sotalol on myocar dial contractility and to test the hypothesis that the class III antiarrhyt hmic effect of sotalol has a reverse use-dependent positive inotropic effec t in the intact heart. BACKGROUND Antiarrhythmic drugs exert significant negative inotropic effect s. Sotalol, a beta-adrenergic blocking agent with class III antiarrhythmic properties, may augment contractility by virtue of its ability to prolong t he action potential duration (APD). METHODS In 10 anesthetized dogs, measurements of left ventricle (LV) peak ( +)dP/dt and simultaneous endocardial action potentials were made during bas eline conditions and after sequential administration of esmolol and sotalol . In addition, electrical and mechanical restitution curves were constructe d at a basic pacing cycle length of 600 ms by introducing a test pulse of a ltered cycle length ranging from 200 ms to 2,000 ms. RESULTS In the steady state pacing experiments, sotalol prolonged the APD i n a reverse use-dependent manner; such an effect was not seen with esmolol. At cycle lengths exceeding 400 ms, LV (+)dP/dt was significantly higher wi th sotalol than it was with esmolol. There was a direct relation between AP D and LV (+)dP/dt with sotalol (r = 0.46, p < 0.001), but there was no sign ificant relation between APD and LV (+)dP/dt with esmolol (r = 0.27, p = NS ). Results in the single beat (restitution) studies were qualitatively simi lar to the steady stare results; APD (at cycle length >400 ms) and LV (+)dP /dt (at cycle length >600 ms) were significantly higher with sotalol than t hey were with esmolol. CONCLUSIONS The reverse use-dependent prolongation of APD by sotalol is ass ociated with a positive inotropic effect. (J Am Coll Cardiol 2000;36:1404-1 0) (C) 2000 by the American College of Cardiology.