Developmental cellular electrophysiologic effects of d-sotalol on canine cardiac Purkinje fibers.
d-Sotalol may be a clinically useful class III antiarrhythmic agent for controlling ventricular arrhythmias in children. Because age-related differences in repolarization currents may contribute to developmental differences in response to antiarrhythmic agents that primarily affect repolarization, the electrophysiologic effects of d-sotalol were compared in Purkinje fibers from neonatal and adult dogs. Significant age-related changes characterized the antiarrhythmic profile of d-sotalol. d-Sotalol (10(-4) M) significantly prolonged the action potential duration of adult Purkinje fibers (310 +/- 8 to 380 +/- 7 ms, p less than 0.01) and neonatal fibers (247 +/- 5 to 342 +/- 9 ms, p less than 0.01). However, the lengthening of action potential duration was significantly greater in the immature age group. d-Sotalol had no significant effect on maximum diastolic potential, action potential amplitude, or phase zero upstroke velocity in normally polarized fibers. In contrast, different electrophysiologic effects were observed in K(+)-depolarized Purkinje fibers. Superfusion of adult K(+)-depolarized fibers with d-sotalol suppressed excitability in five (38%) of 13 fibers and significantly decreased action potential amplitude (88 +/- 2 to 83 +/- 1 mV, p less than 0.05) and phase zero upstroke velocity (180 +/- 14 to 105 +/- 3 V/s, p less than 0.01) in the other eight fibers. The membrane depressant effects observed in the younger age group were significantly less [no suppression of excitability and a smaller decrease in phase zero upstroke velocity (121 +/- 22 to 101 +/- 23 V/s, p less than 0.05). The magnitude of action potential duration prolongation by d-sotalol in K(+)-depolarized fibers was less than in normally polarized fibers.(ABSTRACT TRUNCATED AT 250 WORDS)
Moak
J P
JP
Department of Pediatrics, Baylor College of Medicine, Houston, Texas 77030.
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D000831:Animals, Newborn; D004285:Dogs; D004594:Electrophysiology; D066298:In Vitro Techniques; D011188:Potassium / Q000494:pharmacology; D011690:Purkinje Fibers / Q000187:drug effects* / Q000254:growth & development / Q000502:physiology; D013015:Sotalol / Q000494:pharmacology* / Q000633:toxicity; D016171:Torsades de Pointes / Q000139:chemically induced
D013015:Sotalol; D011188:Potassium