Analysis of electropharmacological effects of AVE0118 on the atria of chronic atrioventricular block dogs: characterization of anti-atrial fibrillatory action by atrial repolarization-delaying agent.
Heart Vessels
; 35(9): 1316-1322, 2020 Sep.
Article
en En
| MEDLINE
| ID: mdl-32346771
ABSTRACT
AVE0118, an inhibitor of IKur, Ito and IK,ACh, was in the drug pipeline for atrial fibrillation. To investigate the limitation of AVE0118 as an anti-atrial fibrillatory drug, we studied its electropharmacological effects particularly focusing on the anti-atrial fibrillatory action as reverse translational research. We adopted the chronic atrioventricular block beagle dogs (n = 4), having a pathophysiology of bradycardia-associated, volume overload-induced chronic heart failure, in which the atrial fibrillation was induced by 10 s of burst pacing on atrial septum. AVE0118 in doses of 0.24 and 1.2 mg/kg, i.v. over 10 min hardly altered electrophysiological variables. Meanwhile, AVE0118 in a dose of 6 mg/kg, i.v. over 10 min delayed the inter-atrial conduction in a frequency-dependent manner and prolonged the atrial effective refractory period in a reverse frequency-dependent manner, whereas it did not significantly alter the duration of atrial fibrillation or its cycle length. The increment of atrial effective refractory period was 3.3 times greater compared with that of ventricular one at a basic cycle length of 400 ms. Torsade de pointes was not induced during the experimental period. Thus, AVE0118 may possess a favorable cardiac safety pharmacological profile, but its weak anti-atrial fibrillatory effect would indicate the limitation of atrial repolarization-delaying agents for suppressing atrial fibrillation.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Periodo Refractario Electrofisiológico
/
Fibrilación Atrial
/
Compuestos de Bifenilo
/
Potenciales de Acción
/
Bloqueadores de los Canales de Potasio
/
Bloqueo Atrioventricular
/
Atrios Cardíacos
/
Frecuencia Cardíaca
/
Antiarrítmicos
Tipo de estudio:
Etiology_studies
/
Prognostic_studies
Límite:
Animals
Idioma:
En
Revista:
Heart Vessels
Asunto de la revista:
CARDIOLOGIA
Año:
2020
Tipo del documento:
Article
País de afiliación:
Japón