Use-dependent electrophysiologic effects of DL-sotalol and modulation by isoproterenol in the human ventricle.
The interaction between dl-sotalol and isoproterenol on the ventricular effective refractory period (VERP) and conduction were examined in an electrophysiologic study of 9 patients at drug-free baseline, after 14 days of dl-sotalol administration (320 mg/day), and after the administration of isoproterenol. In all 9 patients, ventricular tachyarrhythmia could not be induced after dl-sotalol treatment. Isoproterenol was administered as a loading dosage of 0.025 microgram/kg for 5 min with a maintenance dosage of 0.0025 microgram/kg/min. The VERP and the QRS duration were determined at paced cycle lengths of 600, 400 and 300 msec. DL-sotalol and dl-sotalol + isoproterenol had no effect on ventricular conduction at the three cycle lengths. The VERP was significantly prolonged after dl-sotalol treatment at paced cycle lengths of 600 (241 +/- 16 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), but there was a parallel shift of the VERP, suggesting the absence of use-dependent effects on the VERP. The dl-sotalol-induced VERP prolongation was partially reversed by isoproterenol, but it remained significantly prolonged above baseline values at paced cycle lengths of 600 (241 +/- 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 three basic cycle lengths of 600 (16%), 400 (15%) and 300 (20%) msec, indicating the lack of reverse use-dependency. The absence of reverse use-dependency of dl-sotalol on the VERP, even after isoproterenol administration, may be beneficial in the therapy of ventricular tachyarrhythmias and may account in part for the high efficacy of this drug.
Naitoh
N
N
First Department of Internal Medicine, Niigata University School of Medicine, Japan.
Furushima
H
H
Ohira
K
K
Taneda
K
K
Aizawa
Y
Y
D000200:Action Potentials / Q000187:drug effects; D000328:Adult; D000368:Aged; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology* / Q000627:therapeutic use; D002316:Cardiotonic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D004347:Drug Interactions; D004562:Electrocardiography / Q000187:drug effects; D004594:Electrophysiology; D005260:Female; D006801:Humans; D007545:Isoproterenol / Q000494:pharmacology* / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D012032:Refractory Period, Electrophysiological / Q000187:drug effects*; D013015:Sotalol / Q000494:pharmacology* / Q000627:therapeutic use; D017180:Tachycardia, Ventricular / Q000188:drug therapy* / Q000503:physiopathology*; D016276:Ventricular Function / Q000187:drug effects
D000889:Anti-Arrhythmia Agents; D002316:Cardiotonic Agents; D013015:Sotalol; D007545:Isoproterenol