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Animal Models of PAH and Increased Pulmonary Blood Flow

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Pediatric and Congenital Cardiology, Cardiac Surgery and Intensive Care

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Abstract

Pulmonary arterial hypertension (PAH), a progressive pulmonary arteriopathy, is characterized by the development of characteristic neointimal lesions including concentric laminar intimal fibrosis and plexiform lesions.

In PAH associated with congenital heart disease, increased pulmonary blood flow (i.e., systemic-to-pulmonary shunt) is an essential trigger for the occurrence of neointimal lesions and disease development. Although neointimal development is well described histopathologically, the pathogenesis of flow-induced PAH and its typical vascular lesions is largely unknown.

Animal models play a crucial part in giving insight in new pathobiological processes in PAH and possible new therapeutic targets. However, as for any preclinical model, the pathophysiological mechanism and clinical course have to be comparable to the human disease that it is supposed to mimic. This means that animal models mimicking human PAH ideally are characterized by (1) a hit resembling the human disease, (2) specific vascular remodeling that resembles neointimal development in human PAH, and (3) progressive disease development that leads to right ventricular (RV) dysfunction and eventually death.

Therefore, this chapter will discuss currently used animal models for pulmonary hypertension that are of interest for PAH in the pediatric population, specifically PAH associated with congenital heart disease. Since increased pulmonary blood flow is known to be a trigger for PAH development in this population, particular emphasis will be put on models with increased pulmonary blood flow.

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Authors and Affiliations

  1. Department of Pediatric Cardiology, Center for Congenital Heart Diseases, Beatrix Children’s Hospital, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands

    Michael G. Dickinson, Diederik E. van der Feen, Beatrijs Bartelds & Rolf M. F. Berger

Authors
  1. Michael G. Dickinson
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  2. Diederik E. van der Feen
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  3. Beatrijs Bartelds
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  4. Rolf M. F. Berger
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Corresponding author

Correspondence to Michael G. Dickinson .

Editor information

Editors and Affiliations

  1. Children’s Hospital Colorado University of Colorado Denver, School of, Aurora, CO, USA

    Eduardo M. da Cruz

  2. Children's Hospital Colorado University of Colorado School of Medicin, Aurora, CO, USA

    Dunbar Ivy

  3. Department of Cardiac Surgery, German Pediatric Heart Center, Sankt Augustin, Germany

    Viktor Hraska

  4. Pediatric Cardiac Surgery, Children's Hospital Colorado University of Colorado, Aurora, CO, USA

    James Jaggers

Section Editor information

  1. Center for Congenital Heart Diseases, Department of Pediatric Cardiology, Beatrix Children’s Hospital, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands

    Rolf M. F. Berger

  2. Dept. Pediatric Cardiology, Children's Hospital Colorado, Univ. of Colorado, Denver, Aurora, Colorado, USA

    Dunbar Ivy

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Dickinson, M.G., van der Feen, D.E., Bartelds, B., Berger, R.M.F. (2021). Animal Models of PAH and Increased Pulmonary Blood Flow. In: da Cruz, E.M., Ivy, D., Hraska, V., Jaggers, J. (eds) Pediatric and Congenital Cardiology, Cardiac Surgery and Intensive Care. Springer, London. https://doi.org/10.1007/978-1-4471-4999-6_203-2

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  • DOI: https://doi.org/10.1007/978-1-4471-4999-6_203-2

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