USE-DEPENDENT ELECTROPHYSIOLOGIC EFFECTS OF DL-SOTALOL AND MODULATIONBY ISOPROTERENOL IN THE HUMAN VENTRICLE

The interaction between dl-sotalol and isoproterenol on the ventricula r effective refractory period (VERP) and conduction were examined in a n electrophysiologic study of 9 patients at drug-free baseline, after 14 days of dl-sotalol administration (320 mg/day), and after the admin istration of isoproterenol. In all 9 patients, ventricular tachyarrhyt hmia could not be induced after dl-sotalol treatment. Isoproterenol wa s administered as a loading dosage of 0.025 mu g/kg for 5 min with a m aintenance dosage of 0.0025 mu g/kg/min. The VERP and the QRS duration were determined at paced cycle lengths of 600, 400 and 300 msec. DL-s otalol and dl-sotalol + isoproterenol had no effect on ventricular con duction at the three cycle lengths. The VERP was significantly prolong ed after dl-sotalol treatment at paced cycle lengths of 600 (241 +/- 1 6 to 302 +/- 28 msec, p < 0.001), 400 (223 +/- 21 to 280 +/- 23 msec, p < 0.001) and 300 msec (202 +/- 16 to 256 +/- 24 msec, p < 0.005), bu t there was a parallel shift of the VERP, suggesting the absence of us e-dependent effects on the VERP. The dl-sotalol-induced VERP prolongat ion was partially reversed by isoproterenol, but it remained significa ntly prolonged above baseline values at paced cycle lengths of 600 (24 1 +/- 16 to 281 +/- 18 msec, p < 0.01), 400 (223 +/- 21 to 258 +/- 20 msec, p < 0.01) and 300 msec (202 +/- 16 to 247 +/- 22 msec, p < 0.01) . The shortening of the VERP was greater at longer basic cycle lengths (600 and 400 msec) than at the shorter paced cycle length (300 msec, p < .05), but the percentage increase of the VERP was similar at the t hree basic cycle lengths of 600 (16%), 400 (15%) and 300 (20%) msec, i ndicating the lack of reverse use-dependency. The absence of reverse u se-dependency of dl-sotalol on the VERP, even after isoproterenol admi nistration, may be beneficial in the therapy of ventricular tachyarrhy thmias and may account in part for the high efficacy of this drug.