Atrial resting membrane potential confers sodium current sensitivity to propafenone, flecainide and dronedarone.
Heart Rhythm
; 18(7): 1212-1220, 2021 07.
Article
en En
| MEDLINE
| ID: mdl-33737232
ABSTRACT
BACKGROUND:
Although atrial fibrillation ablation is increasingly used for rhythm control therapy, antiarrhythmic drugs (AADs) are commonly used, either alone or in combination with ablation. The effectiveness of AADs is highly variable. Previous work from our group suggests that alterations in atrial resting membrane potential (RMP) induced by low Pitx2 expression could explain the variable effect of flecainide.OBJECTIVE:
The purpose of this study was to assess whether alterations in atrial/cardiac RMP modify the effectiveness of multiple clinically used AADs.METHODS:
The sodium channel blocking effects of propafenone (300 nM, 1 µM), flecainide (1 µM), and dronedarone (5 µM, 10 µM) were measured in human stem cell-derived cardiac myocytes, HEK293 expressing human NaV1.5, primary murine atrial cardiac myocytes, and murine hearts with reduced Pitx2c.RESULTS:
A more positive atrial RMP delayed INa recovery, slowed channel inactivation, and decreased peak action potential (AP) upstroke velocity. All 3 AADs displayed enhanced sodium channel block at more positive atrial RMPs. Dronedarone was the most sensitive to changes in atrial RMP. Dronedarone caused greater reductions in AP amplitude and peak AP upstroke velocity at more positive RMPs. Dronedarone evoked greater prolongation of the atrial effective refractory period and postrepolarization refractoriness in murine Langendorff-perfused Pitx2c+/- hearts, which have a more positive RMP compared to wild type.CONCLUSION:
Atrial RMP modifies the effectiveness of several clinically used AADs. Dronedarone is more sensitive to changes in atrial RMP than flecainide or propafenone. Identifying and modifying atrial RMP may offer a novel approach to enhancing the effectiveness of AADs or personalizing AAD selection.Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Fibrilación Atrial
/
Sodio
/
Propafenona
/
Flecainida
/
Dronedarona
/
Atrios Cardíacos
/
Potenciales de la Membrana
Tipo de estudio:
Diagnostic_studies
/
Prognostic_studies
Límite:
Animals
Idioma:
En
Revista:
Heart Rhythm
Año:
2021
Tipo del documento:
Article