DEVELOPMENTAL EFFECTS OF D-SOTALOL ON ANTEROGRADE AND RETROGRADE ATRIOVENTRICULAR-CONDUCTION IN THE RABBIT

Introduction: These experiments investigate the developmental effects of d-sotalol on standard electrophysiologic parameters of anterograde and retrograde AV conduction in the rabbit. Methods and Results: Using bipolar electrograms and standard pacing techniques, the effects of g raded concentrations of d-sotalol on anterograde and retrograde conduc tion in mature and immature perfused rabbit hearts mere compared. Also , a quantitative assessment of the drug's effects on a rate-dependent property of anterograde AV node (AVN) conduction, termed the ''recover y process,'' was compared in mature and immature rabbit hearts. The ma in developmental electrophysiologic findings of this investigation are : (1) in both the mature and immature rabbit heart, d-sotalol increase s the anterograde conduction time and prolongs refractoriness of the A VN, yet the minimal concentrations of d-sotalol that produce these cha nges are lower in the neonate; (2) d-sotalol increases the anterograde refractory period of the His-Purkinje system in both age groups, but increases anterograde infra-Hisian conduction only in the neonate; (3) 1 X 10(-4) M d-sotalol significantly changes the time constant of the AVN recovery process in the neonate, but not in the adult; (4) for re trograde conduction, slow conduction through the AVN (HA(max)) and inf ra-Hisian region (VHmax) are increased by d-sotalol in the neonate, bu t not in the adult. Conclusions: The findings of this study illustrate that d-sotalol has different effects on parameters of the developing AV conduction system. This implies that there mag be maturational chan ges in the ionic currents that are responsible for anterograde and ret rograde AVN and His-Purkinje conduction.