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.
Hewett
K W
KW
South Carolina Children's Heart Center, Medical University of South Carolina, Charleston 29425, USA.
Le
F K
FK
Martin
K L
KL
Brasington
C R
CR
Piecuch
S
S
Case
C L
CL
D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology*; D001283:Atrioventricular Node / Q000187:drug effects / Q000502:physiology; D002036:Bundle of His / Q000187:drug effects / Q000502:physiology; D004594:Electrophysiology; D006329:Heart Conduction System / Q000187:drug effects* / Q000502:physiology; D010627:Phenethylamines / Q000494:pharmacology*; D011690:Purkinje Fibers / Q000187:drug effects / Q000502:physiology; D000644:Quaternary Ammonium Compounds / Q000494:pharmacology*; D011817:Rabbits; D013424:Sulfanilamides / Q000494:pharmacology*; D013449:Sulfonamides / Q000494:pharmacology*; D000096926:Benzenesulfonamides
D000889:Anti-Arrhythmia Agents; D010627:Phenethylamines; D000644:Quaternary Ammonium Compounds; D013424:Sulfanilamides; D013449:Sulfonamides; C063978:risotilide; D000096926:Benzenesulfonamides; C022799:clofilium; C063533:dofetilide