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.
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.
Can J Cardiol. 2019 Dec;35(12):1762-1771. doi: 10.1016/j.cjca.2019.07.622. Epub 2019 Jul 26.
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.
法洛四联症是最常见的发绀型先天性心脏病。尽管初始手术修复不断改进,但仍存在对长期预后的担忧,这些担忧可能会因右心室功能障碍、右心室不同步和心脏性猝死而变得复杂。导致这些晚期并发症的机制仍不完全清楚。实验动物模型已被开发为临床前步骤,以更好地了解疾病的病理生理学,并开发新的治疗策略。本文总结了迄今为止文献中发表的各种修复性法洛四联症的实验动物模型,旨在更深入地了解可能导致这些已知晚期且有时致命并发症的有害机制。除了根据特定研究的目标、需求和限制分析可用于的动物类型外,本综述还根据研究目标评估了可在我们的模型中重现的功能障碍类型,以及可在其中使用这些模型的不同类型的研究。有鉴于此,我们提出了创建修复性法洛四联症动物模型的决策算法。这种综合还应有助于未来研究的发展和新实验模型的设计,从而更深入地了解这种疾病,同时不要忘记最终目标是扩大未来的治疗措施,以降低这种常见先天性心脏病的发病率和死亡率。