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Canadian Journal of Cardiology

Animal Models of Repaired Tetralogy of Fallot: Current Applications and Future Perspectives

  • Estibaliz Valdeomillos
    Correspondence
    Corresponding author: Dr Estibaliz Valdeomillos, University Hospital of Bordeaux, Avenue Magellan, 33600 Pessac, Bordeaux, France. Tel.: +33-5-57-65-64-65; fax: +33-5-57-65-68-28.
    Affiliations
    Department of Pediatric and Adult Congenital Cardiology, Bordeaux University Hospital (CHU), Bordeaux, France

    IHU Liryc, Electrophysiology and Heart Modeling Institute, Fondation Bordeaux Université, Bordeaux, France

    INSERM, Centre de recherche Cardio-Thoracique de Bordeaux, Bordeaux, France
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  • Zakaria Jalal
    Affiliations
    Department of Pediatric and Adult Congenital Cardiology, Bordeaux University Hospital (CHU), Bordeaux, France

    IHU Liryc, Electrophysiology and Heart Modeling Institute, Fondation Bordeaux Université, Bordeaux, France

    INSERM, Centre de recherche Cardio-Thoracique de Bordeaux, Bordeaux, France
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  • Alexandre Metras
    Affiliations
    IHU Liryc, Electrophysiology and Heart Modeling Institute, Fondation Bordeaux Université, Bordeaux, France

    INSERM, Centre de recherche Cardio-Thoracique de Bordeaux, Bordeaux, France

    Department of Pediatric and Adult Congenital Surgery, Bordeaux University Hospital (CHU), Bordeaux, France
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  • François Roubertie
    Affiliations
    IHU Liryc, Electrophysiology and Heart Modeling Institute, Fondation Bordeaux Université, Bordeaux, France

    INSERM, Centre de recherche Cardio-Thoracique de Bordeaux, Bordeaux, France

    Department of Pediatric and Adult Congenital Surgery, Bordeaux University Hospital (CHU), Bordeaux, France
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  • David Benoist
    Affiliations
    IHU Liryc, Electrophysiology and Heart Modeling Institute, Fondation Bordeaux Université, Bordeaux, France

    INSERM, Centre de recherche Cardio-Thoracique de Bordeaux, Bordeaux, France
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  • Olivier Bernus
    Affiliations
    IHU Liryc, Electrophysiology and Heart Modeling Institute, Fondation Bordeaux Université, Bordeaux, France

    INSERM, Centre de recherche Cardio-Thoracique de Bordeaux, Bordeaux, France
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  • Michel Haïssaguerre
    Affiliations
    IHU Liryc, Electrophysiology and Heart Modeling Institute, Fondation Bordeaux Université, Bordeaux, France

    INSERM, Centre de recherche Cardio-Thoracique de Bordeaux, Bordeaux, France

    Department of Electrophysiology, Cardio-Thoracic Unit, Bordeaux University Hospital (CHU), Bordeaux, France
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  • Pierre Bordachar
    Affiliations
    IHU Liryc, Electrophysiology and Heart Modeling Institute, Fondation Bordeaux Université, Bordeaux, France

    INSERM, Centre de recherche Cardio-Thoracique de Bordeaux, Bordeaux, France

    Department of Electrophysiology, Cardio-Thoracic Unit, Bordeaux University Hospital (CHU), Bordeaux, France
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  • Xavier Iriart
    Affiliations
    Department of Pediatric and Adult Congenital Cardiology, Bordeaux University Hospital (CHU), Bordeaux, France

    IHU Liryc, Electrophysiology and Heart Modeling Institute, Fondation Bordeaux Université, Bordeaux, France

    INSERM, Centre de recherche Cardio-Thoracique de Bordeaux, Bordeaux, France
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  • Jean-Benoit Thambo
    Affiliations
    Department of Pediatric and Adult Congenital Cardiology, Bordeaux University Hospital (CHU), Bordeaux, France

    IHU Liryc, Electrophysiology and Heart Modeling Institute, Fondation Bordeaux Université, Bordeaux, France

    INSERM, Centre de recherche Cardio-Thoracique de Bordeaux, Bordeaux, France
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      Abstract

      Tetralogy of Fallot is the most common cyanotic congenital heart disease. Despite ongoing improvements in the initial surgical repair, there are lingering concerns regarding the long-term outcomes that may be complicated by right ventricular dysfunction, right ventricular dyssynchrony, and sudden cardiac death. The mechanisms leading to these late complications remain incompletely understood. Experimental animal models have been developed as preclinical steps to gain better insight into the pathophysiology of diseases and to develop new therapeutic strategies. This article summarizes the various types of experimental animal models of repaired tetralogy of Fallot published to date in the literature, with the aim of achieving a greater understanding of the deleterious mechanisms that may lead to these known late and sometimes lethal complications. In addition to analysing the type of animals that can be used according to a given study’s objectives, needs, and constraints, the present review also evaluates the type of dysfunction that can be reproduced in our model according to the research objectives, as well as the different types of studies in which these models can be used. In view of all that, we propose a decision algorithm to create an animal model of repaired tetralogy of Fallot. This synthesis should furthermore help in the development of future studies and in the design of new experimental models, thus allowing greater insight into this disease, while not forgetting the ultimate goal of broadening future therapeutic measures to reduce the morbidity and mortality of this prevalent congenital heart disease.

      Résumé

      La tétralogie de Fallot est la cardiopathie congénitale cyanogène la plus fréquente. Malgré les progrès réalisés en matière de réparation chirurgicale (la méthode employée en première intention), l’issue à long terme de la maladie, qui peut être compliquée d’une dysfonction ventriculaire droite, d’une dyssynchronie ventriculaire droite ou d’une mort cardiaque subite, demeure préoccupante. Les mécanismes menant à ces complications tardives ne sont toujours pas bien compris. Des modèles animaux expérimentaux ont été mis au point dans le cadre d’études précliniques afin de mieux comprendre la physiopathologie de la maladie et de concevoir de nouvelles stratégies thérapeutiques. Les auteurs résument les divers types de modèles animaux expérimentaux de tétralogie de Fallot réparée publiés à ce jour, dans le but de mieux comprendre les mécanismes délétères qui peuvent mener à ces complications tardives et parfois mortelles. En plus d’analyser le type d’animal qui peut être utilisé en fonction des objectifs de l’étude, des besoins et des contraintes, nous évaluons les types de dysfonctions qui peuvent être reproduites à l’aide de notre modèle en fonction des objectifs de la recherche, ainsi que les différents types d’études dans lesquelles les modèles peuvent être utilisés. À partir de toutes ces données, nous proposons un algorithme de décision permettant de créer un modèle animal de tétralogie de Fallot réparée. Cette synthèse pourra également servir à concevoir d’autres études et à mettre au point de nouveaux modèles expérimentaux pour mieux comprendre la maladie, sans oublier le but ultime d’élargir l’éventail des options thérapeutiques afin de réduire la morbidité et la mortalité associées à cette cardiopathie congénitale répandue.
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      • Errata
        Canadian Journal of CardiologyVol. 36Issue 6
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          In the article, “Animal Models of Repaired Tetralogy of Fallot: Current Applications and Future Perspectives” (Can J Cardiol 2019;35:1762-1771), the first author’s surname was misspelled as Valdeomillos. The correct spelling is Valdeolmillos.
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