Antiarrhythmic and electrophysiologic effects of ibutilide in a chronic canine model of atrial flutter.
We studied the effects of orally administered ibutilide, a class III antiarrhythmic agent, in a model of reentrant atrial flutter in conscious dogs. After baseline determination of atrial effective refractory period (AERP) and demonstration of reproducible induction of atrial flutter by rapid atrial pacing, 8 dogs received either placebo or one of six doses of ibutilide ranging from 0.1 to 5 mg/kg. Refractory periods and the ability to induce atrial flutter were then assessed at periodic intervals for 8 hours. Ibutilide produced dose-related increases in AERP which were well correlated with prevention of initiation of atrial flutter after doses > or = 0.25 mg/kg. Placebo and 0.1 mg/kg ibutilide had no effect on AERP or the ability to induce atrial flutter. Doses of 0.25 to 1.0 mg/kg ibutilide significantly increased AERP and prevented induction of atrial flutter for 4-6 h. After treatment with 2.5 or 5 mg/kg ibutilide, significant increases in AERP and prevention of induction of atrial flutter persisted throughout the 8-h study period. The cycle length of inducible atrial flutter was significantly increased after administration of 5 mg/kg ibutilide. The results demonstrate oral efficacy of ibutilide with rapid onset of action (in 30-60 min), resulting in increased AERP and prevention of induced atrial flutter in this model.
Buchanan
L V
LV
Cardiovascular Diseases Research, Upjohn Company, Kalamazoo, Michigan 49001.
Turcotte
U M
UM
Kabell
G G
GG
Gibson
J K
JK
D000284:Administration, Oral; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology*; D001282:Atrial Flutter / Q000188:drug therapy*; D002908:Chronic Disease; D004195:Disease Models, Animal; D004285:Dogs; D008297:Male; D010805:Physical Conditioning, Animal; D012146:Rest; D013449:Sulfonamides / Q000494:pharmacology*
D000889:Anti-Arrhythmia Agents; D013449:Sulfonamides; C067192:ibutilide