Cargando…

Challenges in the development of chronic pulmonary hypertension models in large animals

Pulmonary hypertension (PH) results in significant morbidity and mortality. Chronic PH animal models may advance the study of PH’s mechanisms, evolution, and therapy. In this report, we describe the challenges and successes in developing three models of chronic PH in large animals: two models (one c...

Descripción completa

Detalles Bibliográficos
Autores principales: Rothman, Abraham, Wiencek, Robert G., Davidson, Stephanie, Evans, William N., Restrepo, Humberto, Sarukhanov, Valeri, Mann, David
Formato: Online Artículo Texto
Lenguaje:English
Publicado: SAGE Publications 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5448539/
https://www.ncbi.nlm.nih.gov/pubmed/28680575
http://dx.doi.org/10.1086/690099
_version_ 1783239574841982976
author Rothman, Abraham
Wiencek, Robert G.
Davidson, Stephanie
Evans, William N.
Restrepo, Humberto
Sarukhanov, Valeri
Mann, David
author_facet Rothman, Abraham
Wiencek, Robert G.
Davidson, Stephanie
Evans, William N.
Restrepo, Humberto
Sarukhanov, Valeri
Mann, David
author_sort Rothman, Abraham
collection PubMed
description Pulmonary hypertension (PH) results in significant morbidity and mortality. Chronic PH animal models may advance the study of PH’s mechanisms, evolution, and therapy. In this report, we describe the challenges and successes in developing three models of chronic PH in large animals: two models (one canine and one swine) utilized repeated infusions of ceramic microspheres into the pulmonary vascular bed, and the third model employed a surgical aorto-pulmonary shunt. In the canine model, seven dogs underwent microsphere infusions that resulted in progressive elevation of pulmonary arterial pressure over a few months. In this model, pulmonary endoarterial tissue was obtained for histology. In the aorto-pulmonary shunt swine model, 17 pigs developed systemic level pulmonary pressures after 2–3 months. In this model, pulmonary endoarterial tissue was sequentially obtained to assess for changes in gene and microRNA expression. In the swine microsphere infusion model, three pigs developed only a modest chronic increase in pulmonary arterial pressure, despite repeated infusions of microspheres (up to 40 in one animal). The main purpose of this model was for vasodilator testing, which was performed successfully immediately after acute microsphere infusions. Chronic PH in large animal models can be successfully created; however, a model’s characteristics need to match the investigational goals.
format Online
Article
Text
id pubmed-5448539
institution National Center for Biotechnology Information
language English
publishDate 2017
publisher SAGE Publications
record_format MEDLINE/PubMed
spelling pubmed-54485392017-06-08 Challenges in the development of chronic pulmonary hypertension models in large animals Rothman, Abraham Wiencek, Robert G. Davidson, Stephanie Evans, William N. Restrepo, Humberto Sarukhanov, Valeri Mann, David Pulm Circ Research Articles Pulmonary hypertension (PH) results in significant morbidity and mortality. Chronic PH animal models may advance the study of PH’s mechanisms, evolution, and therapy. In this report, we describe the challenges and successes in developing three models of chronic PH in large animals: two models (one canine and one swine) utilized repeated infusions of ceramic microspheres into the pulmonary vascular bed, and the third model employed a surgical aorto-pulmonary shunt. In the canine model, seven dogs underwent microsphere infusions that resulted in progressive elevation of pulmonary arterial pressure over a few months. In this model, pulmonary endoarterial tissue was obtained for histology. In the aorto-pulmonary shunt swine model, 17 pigs developed systemic level pulmonary pressures after 2–3 months. In this model, pulmonary endoarterial tissue was sequentially obtained to assess for changes in gene and microRNA expression. In the swine microsphere infusion model, three pigs developed only a modest chronic increase in pulmonary arterial pressure, despite repeated infusions of microspheres (up to 40 in one animal). The main purpose of this model was for vasodilator testing, which was performed successfully immediately after acute microsphere infusions. Chronic PH in large animal models can be successfully created; however, a model’s characteristics need to match the investigational goals. SAGE Publications 2017-02-01 /pmc/articles/PMC5448539/ /pubmed/28680575 http://dx.doi.org/10.1086/690099 Text en © 2017 by Pulmonary Vascular Research Institute http://creativecommons.org/licenses/by-nc/3.0/ This article is distributed under the terms of the Creative Commons Attribution-NonCommercial 3.0 License (http://www.creativecommons.org/licenses/by-nc/3.0/) which permits non-commercial use, reproduction and distribution of the work without further permission provided the original work is attributed as specified on the SAGE and Open Access pages (https://us.sagepub.com/en-us/nam/open-access-at-sage).
spellingShingle Research Articles
Rothman, Abraham
Wiencek, Robert G.
Davidson, Stephanie
Evans, William N.
Restrepo, Humberto
Sarukhanov, Valeri
Mann, David
Challenges in the development of chronic pulmonary hypertension models in large animals
title Challenges in the development of chronic pulmonary hypertension models in large animals
title_full Challenges in the development of chronic pulmonary hypertension models in large animals
title_fullStr Challenges in the development of chronic pulmonary hypertension models in large animals
title_full_unstemmed Challenges in the development of chronic pulmonary hypertension models in large animals
title_short Challenges in the development of chronic pulmonary hypertension models in large animals
title_sort challenges in the development of chronic pulmonary hypertension models in large animals
topic Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5448539/
https://www.ncbi.nlm.nih.gov/pubmed/28680575
http://dx.doi.org/10.1086/690099
work_keys_str_mv AT rothmanabraham challengesinthedevelopmentofchronicpulmonaryhypertensionmodelsinlargeanimals
AT wiencekrobertg challengesinthedevelopmentofchronicpulmonaryhypertensionmodelsinlargeanimals
AT davidsonstephanie challengesinthedevelopmentofchronicpulmonaryhypertensionmodelsinlargeanimals
AT evanswilliamn challengesinthedevelopmentofchronicpulmonaryhypertensionmodelsinlargeanimals
AT restrepohumberto challengesinthedevelopmentofchronicpulmonaryhypertensionmodelsinlargeanimals
AT sarukhanovvaleri challengesinthedevelopmentofchronicpulmonaryhypertensionmodelsinlargeanimals
AT manndavid challengesinthedevelopmentofchronicpulmonaryhypertensionmodelsinlargeanimals