Antiarrhythmic and electrophysiologic effects of intravenous ibutilide and sotalol in the canine sterile pericarditis model.
BACKGROUND
Atrial arrhythmias are a frequent clinical complication following open heart surgery. We compared the Class III agents d,l-so-talol and ibutilide fumarate in an intravenous cross-over study using the canine atrial sterile pericarditis model.


RESULTS
We studied pacing-induced sustained atrial flutter over a 7-day post-surgical period in conscious dogs, alternating analysis of ibutilide (1.0 to 30.0 micrograms/kg) and d,l-sotalol (0.1 to 3.0 mg/kg). Ibutilide significantly increased atrial flutter cycle length (AFL CL) 11 +/- 2 msec and atrial effective refractory period (AERP) 13 +/- 2 msec, and terminated atrial flutter in all cases (n = 12) following a mean dose of 6 +/- 2 micrograms/kg. Plasma concentrations of ibutilide were 53 +/- 13 ng/mL. Ventricular effective refractory period (VERP) was not significantly affected (4 +/- 2 msec). Following termination with ibutilide, atrial flutter could be reinitiated in 1 of 12 trials, and was nonsustained (40-sec duration). Sotalol significantly increased AFL CL 23 +/- 3 msec and terminated atrial flutter in 8 of 12 trials following a mean dose of 1.5 +/- 0.4 mg/kg. AERP and VERP were significantly increased 20 +/- 6 and 12 +/- 2 msec, respectively. The incidence of reinduced atrial flutter was 9 of 12 trials (P < or = 0.05 vs ibutilide) (7 nonsustained 57 +/- 7 sec duration, and 2 sustained). Sotalol failed to terminate atrial flutter in two dogs on days 1 and 5, despite increases in AFL CL (21 +/- 8 msec) and AERP (16 +/- 9 msec), whereas on day 3, ibutilide (20 +/- 7 micrograms/kg) terminated atrial flutter in those two dogs while increasing AFL CL and AERP 18 +/- 6 and 15 +/- 0 msec, respectively.


CONCLUSIONS
Both sotalol and ibutilide terminate atrial flutter in this model. Ibutilide converted atrial flutter in dogs in which sotalol was not successful. Following atrial flutter termination, ibutilide had a lower incidence of reinduced arrhythmias compared to sotalol. Ibutilide produced atrial antiarrhythmic effects while having no significant electrophysiologic effects on the ventricle.
Buchanan
L V
LV
Department of Cardiovascular Pharmacology, Upjohn Laboratories, Kalamazoo, Michigan, USA.
LeMay
R J
RJ
Walters
R R
RR
Hsu
C Y
CY
Brunden
M N
MN
Gibson
J K
JK
D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000008:administration & dosage*; D001282:Atrial Flutter / Q000188:drug therapy* / Q000209:etiology / Q000503:physiopathology; D018592:Cross-Over Studies; D004285:Dogs; D004562:Electrocardiography; D007262:Infusions, Intravenous; D008297:Male; D010493:Pericarditis / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology; D013015:Sotalol / Q000008:administration & dosage*; D013449:Sulfonamides / Q000008:administration & dosage*; D013611:Tachycardia, Atrioventricular Nodal Reentry / Q000517:prevention & control*
D000889:Anti-Arrhythmia Agents; D013449:Sulfonamides; C067192:ibutilide; D013015:Sotalol