Electrophysiological effects of ranolazine in a goat model of lone atrial fibrillation.
Heart Rhythm
; 18(4): 615-622, 2021 04.
Article
em En
| MEDLINE
| ID: mdl-33232809
ABSTRACT
BACKGROUND:
There is still an unmet need for pharmacologic treatment of atrial fibrillation (AF) with few effects on ventricular electrophysiology. Ranolazine is an antiarrhythmic drug reported to have strong atrial selectivity.OBJECTIVE:
The purpose of this study was to investigate the electrophysiological effects of ranolazine in atria with AF-induced electrical remodeling in a model of lone AF in awake goats.METHODS:
Electrode patches were implanted on the atrial epicardium of 8 Dutch milk goats. Experiments were performed at baseline and after 2 and 14 days of electrically maintained AF. Several electrophysiological parameters and AF episode duration were measured during infusion of vehicle and different doses of ranolazine (target plasma levels 4, 8, and 16 µM, respectively).RESULTS:
The highest dose of ranolazine significantly prolonged atrial effective refractory period and decreased atrial conduction velocity at baseline and after 2 days of AF. After 2 weeks of AF, ranolazine prolonged the p5 and p50 of AF cycle length distribution in a dose-dependent manner but was not effective in restoring sinus rhythm. No adverse ventricular arrhythmic events (eg, premature ventricular beats or signs of hemodynamic instability) were observed during infusion of ranolazine at any point in the study.CONCLUSION:
The lowest investigated dose of ranolazine, which is expected to block both late INa and atrial peak INa, had no effect on the investigated electrophysiological parameters. The highest dose affected both atrial and ventricular electrophysiological parameters at different stages of AF-induced remodeling but was not efficacious in cardioverting AF to sinus rhythm in a goat model of lone AF.Palavras-chave
Texto completo:
1
Bases de dados:
MEDLINE
Assunto principal:
Fibrilação Atrial
/
Remodelamento Atrial
/
Ranolazina
/
Átrios do Coração
/
Antiarrítmicos
Limite:
Animals
Idioma:
En
Revista:
Heart Rhythm
Ano de publicação:
2021
Tipo de documento:
Article
País de afiliação:
Alemanha