title: Proarrhythmic remodelling of the right ventricle in a porcine model of repaired tetralogy of Fallot.
abstract: The growing adult population with surgically corrected tetralogy of Fallot (TOF) is at risk of arrhythmias and sudden cardiac death. We sought to investigate the contribution of right ventricular (RV) structural and electrophysiological remodelling to arrhythmia generation in a preclinical animal model of repaired TOF (rTOF).
  
  
  
  Pigs mimicking rTOF underwent cardiac MRI functional characterisation and presented with pulmonary regurgitation, RV hypertrophy, dilatation and dysfunction compared with Sham-operated animals (Sham). Optical mapping of rTOF RV-perfused wedges revealed a significant prolongation of RV activation time with slower conduction velocities and regions of conduction slowing well beyond the surgical scar. A reduced protein expression and lateralisation of Connexin-43 were identified in rTOF RVs. A remodelling of extracellular matrix-related gene expression and an increase in collagen content that correlated with prolonged RV activation time were also found in these animals. RV action potential duration (APD) was prolonged in the epicardial anterior region at early and late repolarisation level, thus contributing to a greater APD heterogeneity and to altered transmural and anteroposterior APD gradients in rTOF RVs. APD remodelling involved changes in Kv4.3 and MiRP1 expression. Spontaneous arrhythmias were more frequent in rTOF wedges and more complex in the anterior than in the posterior RV.
  
  
  
  Significant remodelling of RV conduction and repolarisation properties was found in pigs with rTOF. This remodelling generates a proarrhythmic substrate likely to facilitate re-entries and to contribute to sudden cardiac death in patients with rTOF.
authors.affiliation: IHU LIRYC, L'Institut de Rythmologie et Modélisation Cardiaque, Fondation Bordeaux Université, Bordeaux, France.|Inserm U1045, Centre de Recherche Cardio-Thoracique de Bordeaux, Université de Bordeaux, Bordeaux, France.
authors.forename: David
authors.initials: D
authors.lastname: Benoist
authors.affiliation: IHU LIRYC, L'Institut de Rythmologie et Modélisation Cardiaque, Fondation Bordeaux Université, Bordeaux, France.|Inserm U1045, Centre de Recherche Cardio-Thoracique de Bordeaux, Université de Bordeaux, Bordeaux, France.
authors.forename: Virginie
authors.initials: V
authors.lastname: Dubes
authors.affiliation: IHU LIRYC, L'Institut de Rythmologie et Modélisation Cardiaque, Fondation Bordeaux Université, Bordeaux, France.|Inserm U1045, Centre de Recherche Cardio-Thoracique de Bordeaux, Université de Bordeaux, Bordeaux, France.|CHU de Bordeaux, Hôpital Cardiologique du Haut-Lévêque, Pessac, France.
authors.forename: François
authors.initials: F
authors.lastname: Roubertie
authors.affiliation: IHU LIRYC, L'Institut de Rythmologie et Modélisation Cardiaque, Fondation Bordeaux Université, Bordeaux, France.|Inserm U1045, Centre de Recherche Cardio-Thoracique de Bordeaux, Université de Bordeaux, Bordeaux, France.|Max Delbrück Center for Molecular Medicine, Mathematical Cell Physiology, Berlin, Germany.
authors.forename: Stephen H
authors.initials: SH
authors.lastname: Gilbert
authors.affiliation: IHU LIRYC, L'Institut de Rythmologie et Modélisation Cardiaque, Fondation Bordeaux Université, Bordeaux, France.|Inserm U1045, Centre de Recherche Cardio-Thoracique de Bordeaux, Université de Bordeaux, Bordeaux, France.
authors.forename: Sabine
authors.initials: S
authors.lastname: Charron
authors.affiliation: IHU LIRYC, L'Institut de Rythmologie et Modélisation Cardiaque, Fondation Bordeaux Université, Bordeaux, France.|Inserm U1045, Centre de Recherche Cardio-Thoracique de Bordeaux, Université de Bordeaux, Bordeaux, France.
authors.forename: Marion
authors.initials: M
authors.lastname: Constantin
authors.affiliation: IHU LIRYC, L'Institut de Rythmologie et Modélisation Cardiaque, Fondation Bordeaux Université, Bordeaux, France.|Inserm U1045, Centre de Recherche Cardio-Thoracique de Bordeaux, Université de Bordeaux, Bordeaux, France.|Institute of Biomedical Engineering, Department of Engineering Science, University of Oxford, Oxford, UK.
authors.forename: Delphine
authors.initials: D
authors.lastname: Elbes
authors.affiliation: Plateforme Technologique d'Innovation Biomédicale, Université de Bordeaux, Pessac, France.
authors.forename: Delphine
authors.initials: D
authors.lastname: Vieillot
authors.affiliation: IHU LIRYC, L'Institut de Rythmologie et Modélisation Cardiaque, Fondation Bordeaux Université, Bordeaux, France.|Inserm U1045, Centre de Recherche Cardio-Thoracique de Bordeaux, Université de Bordeaux, Bordeaux, France.
authors.forename: Bruno
authors.initials: B
authors.lastname: Quesson
authors.affiliation: IHU LIRYC, L'Institut de Rythmologie et Modélisation Cardiaque, Fondation Bordeaux Université, Bordeaux, France.|Inserm U1045, Centre de Recherche Cardio-Thoracique de Bordeaux, Université de Bordeaux, Bordeaux, France.|CHU de Bordeaux, Hôpital Cardiologique du Haut-Lévêque, Pessac, France.
authors.forename: Hubert
authors.initials: H
authors.lastname: Cochet
authors.affiliation: IHU LIRYC, L'Institut de Rythmologie et Modélisation Cardiaque, Fondation Bordeaux Université, Bordeaux, France.|Inserm U1045, Centre de Recherche Cardio-Thoracique de Bordeaux, Université de Bordeaux, Bordeaux, France.|CHU de Bordeaux, Hôpital Cardiologique du Haut-Lévêque, Pessac, France.
authors.forename: Michel
authors.initials: M
authors.lastname: Haïssaguerre
authors.affiliation: Inserm U1211, Maladies Rares: Génétique et Métabolisme, Université de Bordeaux, Bordeaux, France.
authors.forename: Caroline
authors.initials: C
authors.lastname: Rooryck
authors.affiliation: IHU LIRYC, L'Institut de Rythmologie et Modélisation Cardiaque, Fondation Bordeaux Université, Bordeaux, France.|Inserm U1045, Centre de Recherche Cardio-Thoracique de Bordeaux, Université de Bordeaux, Bordeaux, France.|CHU de Bordeaux, Hôpital Cardiologique du Haut-Lévêque, Pessac, France.
authors.forename: Pierre
authors.initials: P
authors.lastname: Bordachar
authors.affiliation: IHU LIRYC, L'Institut de Rythmologie et Modélisation Cardiaque, Fondation Bordeaux Université, Bordeaux, France.|Inserm U1045, Centre de Recherche Cardio-Thoracique de Bordeaux, Université de Bordeaux, Bordeaux, France.|CHU de Bordeaux, Hôpital Cardiologique du Haut-Lévêque, Pessac, France.
authors.forename: Jean-Benoit
authors.initials: JB
authors.lastname: Thambo
authors.affiliation: IHU LIRYC, L'Institut de Rythmologie et Modélisation Cardiaque, Fondation Bordeaux Université, Bordeaux, France.|Inserm U1045, Centre de Recherche Cardio-Thoracique de Bordeaux, Université de Bordeaux, Bordeaux, France.
authors.forename: Olivier
authors.initials: O
authors.lastname: Bernus
mesh_terms: D000200:Action Potentials; D000818:Animals; D001145:Arrhythmias, Cardiac / Q000209:etiology* / Q000378:metabolism / Q000503:physiopathology; D006348:Cardiac Surgical Procedures / Q000009:adverse effects*; D018031:Connexin 43 / Q000378:metabolism; D004195:Disease Models, Animal; D006329:Heart Conduction System / Q000378:metabolism / Q000503:physiopathology*; D006339:Heart Rate; D008279:Magnetic Resonance Imaging; D051672:Shal Potassium Channels / Q000378:metabolism; D034421:Sus scrofa; D013771:Tetralogy of Fallot / Q000150:complications / Q000378:metabolism / Q000503:physiopathology / Q000601:surgery*; D013997:Time Factors; D016278:Ventricular Function, Right; D020257:Ventricular Remodeling; D056969:Voltage-Sensitive Dye Imaging
chemical_list: D018031:Connexin 43; D051672:Shal Potassium Channels