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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...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
SAGE Publications
2017
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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 |
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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 |
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