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.
First Department of Internal Medicine, Niigata University School of Medicine, Japan.
N
N
Naitoh
H
H
Furushima
K
K
Ohira
K
K
Taneda
Y
Y
Aizawa
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