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The newborn sheep translational model for pulmonary arterial hypertension of the neonate at high altitude

Published online by Cambridge University Press:  24 July 2020

Alejandro Gonzaléz-Candia Open the ORCID record for Alejandro Gonzaléz-Candia [Opens in a new window] ,
Alejandro A. Candia ,
Germán Ebensperger ,
Roberto V. Reyes ,
Aníbal J. Llanos  and
Emilio A. Herrera
Alejandro Gonzaléz-Candia
Affiliation:
Laboratory of Vascular Function and Reactivity, Pathophysiology Program, ICBM, Faculty of Medicine, Universidad de Chile, Santiago, Chile
Alejandro A. Candia
Affiliation:
Laboratory of Vascular Function and Reactivity, Pathophysiology Program, ICBM, Faculty of Medicine, Universidad de Chile, Santiago, Chile Department for the Woman and Newborn Health Promotion, Universidad de Chile, Santiago, Chile
Germán Ebensperger
Affiliation:
Pathophysiology Program, ICBM, Faculty of Medicine, Universidad de Chile, Santiago, Chile
Roberto V. Reyes
Affiliation:
Pathophysiology Program, ICBM, Faculty of Medicine, Universidad de Chile, Santiago, Chile International Center for Andean Studies (INCAS), Universidad de Chile, Putre, Chile
Aníbal J. Llanos
Affiliation:
Pathophysiology Program, ICBM, Faculty of Medicine, Universidad de Chile, Santiago, Chile International Center for Andean Studies (INCAS), Universidad de Chile, Putre, Chile
Emilio A. Herrera*
Affiliation:
Laboratory of Vascular Function and Reactivity, Pathophysiology Program, ICBM, Faculty of Medicine, Universidad de Chile, Santiago, Chile Pathophysiology Program, ICBM, Faculty of Medicine, Universidad de Chile, Santiago, Chile International Center for Andean Studies (INCAS), Universidad de Chile, Putre, Chile
*
Address for correspondence: Emilio A. Herrera, Laboratorio de Función y Reactividad Vascular, Programa de Fisiopatología, ICBM, Facultad de Medicina, Universidad de Chile, Av. Salvador 486, Providencia 7500922, Santiago, Chile. Email: eherrera@med.uchile.cl
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Abstract

Chronic hypoxia during gestation induces greater occurrence of perinatal complications such as intrauterine growth restriction, fetal hypoxia, newborn asphyxia, and respiratory distress, among others. This condition may also cause a failure in the transition of the fetal to neonatal circulation, inducing pulmonary arterial hypertension of the neonate (PAHN), a syndrome that involves pulmonary vascular dysfunction, increased vasoconstrictor tone and pathological remodeling. As this syndrome has a relatively low prevalence in lowlands (~7 per 1000 live births) and very little is known about its prevalence and clinical evolution in highlands (above 2500 meters), our understanding is very limited. Therefore, studies on appropriate animal models have been crucial to comprehend the mechanisms underlying this pathology. Considering the strengths and weaknesses of any animal model of human disease is fundamental to achieve an effective and meaningful translation to clinical practice. The sheep model has been used to study the normal and abnormal cardiovascular development of the fetus and the neonate for almost a century. The aim of this review is to highlight the advances in our knowledge on the programming of cardiopulmonary function with the use of high-altitude newborn sheep as a translational model of PAHN.

Keywords

Hypoxiahypobariaepigeneticshigh altitudeDOHaD
Type
Review
Information
Journal of Developmental Origins of Health and Disease , Volume 11 , Issue 5 , October 2020 , pp. 452 - 463
Copyright
© Cambridge University Press and the International Society for Developmental Origins of Health and Disease 2020

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