Changes in atrioventricular conduction properties with refractory-period modulation.

Dofetilide, clofilium, and risotilide, three drugs known to prolong cardiac action potentials and refractory periods, were studied by using a perfused isolated rabbit heart preparation with intermittent premature pacing and bipolar surface electrograms. The rate-related effects of these drugs on atrioventricular (AV) conduction were tested by pacing at a long (400 ms) and a short (250 ms) basic cycle length (BCL). All three drugs increased refractory periods in a concentration-dependent manner in most segments of the AV axis. The maximal atrio-His (AH) conduction interval (AHmax) and delta AH (AHmax - AHmin) produced by premature pacing was decreased by the highest concentration of each drug at the 400-ms BCL, whereas only clofilium reduced AHmax and delta AH at the 250-ms BCL. Changes in delta AH correlated best with changes in the atrial functional refractory period. The His-Purkinje system conduction interval (HV), represented by delta HV, was unaffected by any drug at either BCL. These results show that if atrial or nodal refractory periods are increased sufficiently, AHmax but not AHmin was decreased at the 400-ms BCL. Because dofetilide and risotilide did not affect AHmax at the 250-ms BCL, these drugs may be less effective at preventing AV nodal reentrant tachycardias than a drug such as clofilium that displays less rate dependency.

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 graded concentrations of d-sotalol on anterograde and retrograde conduction in mature and immature perfused rabbit hearts were compared. Also, a quantitative assessment of the drug's effects on a rate-dependent property of anterograde AV node (AVN) conduction, termed the "recovery process," was compared in mature and immature rabbit hearts. The main developmental electrophysiologic findings of this investigation are: (1) in both the mature and immature rabbit heart, d-sotalol increases the anterograde conduction time and prolongs refractoriness of the AVN, yet the minimal concentrations of d-sotalol that produce these changes 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 retrograde conduction, slow conduction through the AVN (HAmax) and infra-Hisian region (VHmax) are increased by d-sotalol in the neonate, but 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 may be maturational changes in the ionic currents that are responsible for anterograde and retrograde AVN and His-Purkinje conduction.