Antiarrhythmic Effects of Combining Dofetilide and Ranolazine in a Model of Acutely Induced Atrial Fibrillation in Horses

Abstract

Antiarrhythmic compounds against atrial fibrillation (AF) often have reduced efficacy and may display cardiac and/or non-cardiac toxicity. Efficacy can be improved by combining two compounds with distinct mechanisms, and it may be possible to use lower doses of each compound, thereby reducing the likelihood of adverse side-effects. The purpose of this study was to investigate whether the effective doses of dofetilide and ranolazine can be reduced if the drugs are combined. Dofetilide, ranolazine and a combination of these were administered in four incremental dosing regimens to horses with acutely pacing-induced AF. Time to cardioversion, atrial effective refractory period (aERP), and AF vulnerability and duration were assessed. Out of eight horses, six cardioverted to sinus rhythm following infusion with a combination of 0.889 µg/kg dofetilide and 0.104 mg/kg ranolazine. Two horses cardioverted with 0.104 mg/kg ranolazine alone, and three cardioverted with 0.889 µg/kg dofetilide alone. The combination therapy decreased AF vulnerability (P < 0.05) and AF duration (P < 0.05). No change in aERP was detected with any of the drugs. The combination of dofetilide and ranolazine showed increased antiarrhythmic effects on acutely induced AF in horses, affecting time to cardioversion, AF vulnerability and AF duration. This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND) , where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal.