Cellular electrophysiologic responses of isolated neonatal and adult cardiac fibers to d-sotalol.
The short-term cellular electrophysiologic actions of d-sotalol on isolated neonatal and adult canine ventricular myocardium and Purkinje fibers were evaluated using standard microelectrode techniques. d-Sotalol, 10(-6) to 10(-4)M, had no effects on action potential amplitude, maximal diastolic potential or action potential upstroke velocity (Vmax) in any neonatal or adult preparation. In five adult myocardial preparations, d-sotalol produced concentration-dependent increases in action potential duration at 50% (APD50) and 90% (APD90) repolarization and effective refractory period. In six neonatal myocardial preparations, d-sotalol produced a biphasic response; APD50, APD90 and effective refractory period decreased at 10(-6) and 10(-5)M. At 10(-4)M, these values increased significantly but to a lesser extent compared with values in adults. In seven adult Purkinje fibers, d-Sotalol significantly increased APD50, APD90 and effective refractory period in a concentration-dependent manner. All six neonatal Purkinje fibers responded in a biphasic manner, with values for APD50, APD90 and effective refractory period being less than control at 10(-6)M and near control values at 10(-5)M. At 10(-4)M, these variables were significantly increased, but to a lesser extent than in adult preparations. Our data confirm the typical class III effects of d-sotalol in adult cardiac tissues. The shortening of repolarization and refractoriness at lower drug concentrations in developing cardiac tissues may relate to age-dependent differences in cellular ionic function and basic electrophysiology.
Yabek
S M
SM
Department of Pediatrics, University of New Mexico School of Medicine, Albuquerque 87131.
Kato
R
R
Ikeda
N
N
Singh
B N
BN
D000200:Action Potentials / Q000187:drug effects; D000704:Analysis of Variance; D000818:Animals; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D004594:Electrophysiology; D005260:Female; D006329:Heart Conduction System / Q000187:drug effects*; D007425:Intracellular Membranes / Q000502:physiology*; D008297:Male; D008839:Microelectrodes; D009206:Myocardium / Q000378:metabolism; D011690:Purkinje Fibers / Q000187:drug effects*; D013015:Sotalol / Q000494:pharmacology*; D013997:Time Factors
D013015:Sotalol