Electropharmacology of sotalol in patients with Wolff-Parkinson-White syndrome.
The beta-adrenoceptor-blocking and class III effects of sotalol were assessed in 11 patients with inducible orthodromic reciprocating tachycardia. Serum sotalol concentration, maximum exercise heart rate, and electrophysiologic study data were obtained at control, at the beta-adrenoceptor-blocking dosage (407 +/- 149 mg/day, 1.4 +/- 0.5 micrograms/ml), and at the maximum well-tolerated dosage (924 +/- 337 mg/day, 3.2 +/- 1.3 micrograms/ml). Class III effects (increases in anterograde and retrograde accessory connection effective refractory periods, ventricular effective refractory period, and the QT interval during fixed-rate atrial pacing) were evident at the beta-adrenoceptor-blocking dosage of sotalol and became more marked at the maximum well-tolerated dosage. For example, the mean anterograde accessory connection effective refractory period was significantly increased over control (272 +/- 41 msec) by the beta-adrenoceptor blocker (324 +/- 52 msec) and was further significantly increased by the maximum well-tolerated dose (364 +/- 37 msec). Similarly, the minimum preexcited RR interval during atrial fibrillation was increased in all patients at each dosage tested. Antiarrhythmic efficacy, defined by the absence of inducible, sustained, orthodromic reciprocating tachycardia and a minimum preexcited RR interval during atrial fibrillation of 300 msec or greater, was achieved in four patients at the beta-adrenoceptor-blocking dosage and in another four patients at the maximum well-tolerated dosage. These eight patients received long-term sotalol therapy and none has had recurrent, sustained reciprocating tachycardia during 15 +/- 12 months of follow-up.(ABSTRACT TRUNCATED AT 250 WORDS)
Mitchell
L B
LB
Department of Medicine, Foothills General Hospital, Calgary, Alberta, Canada.
Wyse
D G
DG
Duff
H J
HJ
D000328:Adult; D001283:Atrioventricular Node / Q000187:drug effects / Q000503:physiopathology; D004305:Dose-Response Relationship, Drug; D004562:Electrocardiography; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D011943:Receptors, Adrenergic, beta / Q000187:drug effects; D013015:Sotalol / Q000097:blood / Q000494:pharmacology / Q000627:therapeutic use*; D014927:Wolff-Parkinson-White Syndrome / Q000188:drug therapy* / Q000503:physiopathology
D011943:Receptors, Adrenergic, beta; D013015:Sotalol