Different effects of flecainide on atrioventricular conduction properties in the adult and immature rabbit heart.
The influence of flecainide (0.1, 0.5, 1.0, and 2.0 micrograms/mL) on atrioventricular (AV) conduction was studied in neonatal and adult perfused rabbit hearts using extracellular bipolar surface electrograms and premature atrial and ventricular pacing. Flecainide produced a concentration and rate-related increase in the steady-state nodal conduction (AHmin) and an increase in slow AH conduction (AHmax) in both age groups. The drug produced significant increases in the refractory periods of the atrium, AV node, His-Purkinje system, and ventricular myocardium. The neonatal refractory periods were significantly greater at lower or the same drug concentrations than those of the adult. The neonatal Wenckebach cycle length was significantly greater with a lower concentration of drug (0.5 microgram/mL) than was the adult Wenckebach cycle length. The His-Purkinje system steady-state conduction time (HVmin) was increased by a lower concentration of drug in the neonate (0.5 microgram/mL) as compared with 2.0 micrograms/mL in the adult. These data show that across a wide range of AV conduction parameters, the neonatal preparations responded to a lower concentration of flecainide than did the adult preparations. These findings may, in part, be the basis for the reported greater efficacy of the drug in children than in adults.
Han
H S
HS
Division of Pediatric Cardiology, Medical University of South Carolina, Charleston 29425, USA.
Hewett
K W
KW
McKay
C A
CA
Gillette
P C
PC
Case
C L
CL
D000375:Aging / Q000502:physiology; D000818:Animals; D000831:Animals, Newborn; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology*; D001283:Atrioventricular Node / Q000187:drug effects* / Q000254:growth & development; D005424:Flecainide / Q000494:pharmacology*; D006329:Heart Conduction System / Q000187:drug effects* / Q000254:growth & development; D066298:In Vitro Techniques; D011690:Purkinje Fibers / Q000502:physiology; D011817:Rabbits; D012032:Refractory Period, Electrophysiological / Q000187:drug effects
D000889:Anti-Arrhythmia Agents; D005424:Flecainide