title: Antiarrhythmic drugs preferentially produce conduction block at the area of slow conduction in the re-entrant circuit of canine atrial flutter: comparative study of disopyramide, flecainide, and E-4031.
abstract: OBJECTIVE
  The aim was to test whether antiarrhythmic drugs preferentially suppressed conduction in the area of slow conduction in the re-entrant circuit.
  
  
  METHODS
  Intravenous disopyramide [n = 8, plasma concentrations: 1.4 (SEM 0.2) micrograms.ml-1], flecainide [n = 8, 0.6(0.1) micrograms.ml-1], and E-4031, a new class III antiarrhythmic drug [n = 8, 5.6(1.0) ng.ml-1], were investigated for their effects on atrial flutter due to re-entry in dogs with intercaval crush. In three dogs, detailed atrial activation sequence during atrial flutter was determined with a hand held bipolar electrode and an epicardial isochronal map was drawn.
  
  
  METHODS
  24 anaesthetised adult mongrel dogs were used.
  
  
  RESULTS
  There was an area of slow conduction during atrial flutter in the low right atrium. Atrial flutter was terminated in all dogs except for one treated with flecainide. In 92% of the dogs, conduction block occurred in the low right atrium in which the area of slow conduction was located. Increase in local conduction time was greater in the area of slow conduction than other parts of the atria (percent ratio to the increase in cycle length of atrial flutter: 63% with disopyramide, 52% with flecainide, and 99% with E-4031).
  
  
  CONCLUSIONS
  These data suggested antiarrhythmic drugs preferentially suppressed conduction at the area of slow conduction in the re-entrant circuit leading to termination of atrial flutter in this canine model, irrespective of electrophysiological effects of antiarrhythmic drugs.
authors.affiliation: Second Department of Internal Medicine, Tokyo University Hospital, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Inoue
authors.forename: T
authors.initials: T
authors.lastname: Yamashita
authors.forename: M
authors.initials: M
authors.lastname: Usui
authors.forename: A
authors.initials: A
authors.lastname: Nozaki
authors.forename: T
authors.initials: T
authors.lastname: Sugimoto
mesh_terms: D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology*; D001282:Atrial Flutter / Q000503:physiopathology*; D004206:Disopyramide / Q000494:pharmacology; D004285:Dogs; D005424:Flecainide / Q000494:pharmacology; D006329:Heart Conduction System / Q000187:drug effects* / Q000503:physiopathology; D010880:Piperidines / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology
chemical_list: D000889:Anti-Arrhythmia Agents; D010880:Piperidines; D011725:Pyridines; C063968:E 4031; D004206:Disopyramide; D005424:Flecainide