Combination proximal pulmonary artery coiling and distal embolization induces chronic elevations in pulmonary artery pressure in Swine.
Pulmonary hypertension (PH) is associated with aberrant vascular remodeling and right ventricular (RV) dysfunction that contribute to early mortality. Large animal models that recapitulate human PH are essential for mechanistic studies and evaluating novel therapies; however, these models are not re...
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Format: | Article |
Language: | English |
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Public Library of Science (PLoS)
2015-01-01
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Series: | PLoS ONE |
Online Access: | http://europepmc.org/articles/PMC4414513?pdf=render |
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author | Jaume Aguero Kiyotake Ishikawa Kenneth M Fish Nadjib Hammoudi Lahouaria Hadri Ana Garcia-Alvarez Borja Ibanez Valentin Fuster Roger J Hajjar Jane A Leopold |
author_facet | Jaume Aguero Kiyotake Ishikawa Kenneth M Fish Nadjib Hammoudi Lahouaria Hadri Ana Garcia-Alvarez Borja Ibanez Valentin Fuster Roger J Hajjar Jane A Leopold |
author_sort | Jaume Aguero |
collection | DOAJ |
description | Pulmonary hypertension (PH) is associated with aberrant vascular remodeling and right ventricular (RV) dysfunction that contribute to early mortality. Large animal models that recapitulate human PH are essential for mechanistic studies and evaluating novel therapies; however, these models are not readily accessible to the field owing to the need for advanced surgical techniques or hypoxia. In this study, we present a novel swine model that develops cardiopulmonary hemodynamics and structural changes characteristic of chronic PH. This percutaneous model was created in swine (n=6) by combining distal embolization of dextran beads with selective coiling of the lobar pulmonary arteries (2 procedures per lung over 4 weeks). As controls, findings from this model were compared with those from a standard weekly distal embolization model (n=6) and sham animals (n=4). Survival with the combined embolization model was 100%. At 8 weeks after the index procedure, combined embolization procedure animals had increased mean pulmonary artery pressure (mPA) and pulmonary vascular resistance (PVR) compared to the controls with no effect on left heart or systemic pressures. RV remodeling and RV dysfunction were also present with a decrease in the RV ejection fraction, increase in the myocardial performance index, impaired longitudinal function, as well as cardiomyocyte hypertrophy, and interstitial fibrosis, which were not present in the controls. Pulmonary vascular remodeling occurred in both embolization models, although only the combination embolization model had a decrease in pulmonary capacitance. Taken together, these cardiopulmonary hemodynamic and structural findings identify the novel combination embolization swine model as a valuable tool for future studies of chronic PH. |
first_indexed | 2024-04-13T13:11:04Z |
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institution | Directory Open Access Journal |
issn | 1932-6203 |
language | English |
last_indexed | 2024-04-13T13:11:04Z |
publishDate | 2015-01-01 |
publisher | Public Library of Science (PLoS) |
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series | PLoS ONE |
spelling | doaj.art-c0f794946ac34527a62e5b1dbfe7431e2022-12-22T02:45:36ZengPublic Library of Science (PLoS)PLoS ONE1932-62032015-01-01104e012452610.1371/journal.pone.0124526Combination proximal pulmonary artery coiling and distal embolization induces chronic elevations in pulmonary artery pressure in Swine.Jaume AgueroKiyotake IshikawaKenneth M FishNadjib HammoudiLahouaria HadriAna Garcia-AlvarezBorja IbanezValentin FusterRoger J HajjarJane A LeopoldPulmonary hypertension (PH) is associated with aberrant vascular remodeling and right ventricular (RV) dysfunction that contribute to early mortality. Large animal models that recapitulate human PH are essential for mechanistic studies and evaluating novel therapies; however, these models are not readily accessible to the field owing to the need for advanced surgical techniques or hypoxia. In this study, we present a novel swine model that develops cardiopulmonary hemodynamics and structural changes characteristic of chronic PH. This percutaneous model was created in swine (n=6) by combining distal embolization of dextran beads with selective coiling of the lobar pulmonary arteries (2 procedures per lung over 4 weeks). As controls, findings from this model were compared with those from a standard weekly distal embolization model (n=6) and sham animals (n=4). Survival with the combined embolization model was 100%. At 8 weeks after the index procedure, combined embolization procedure animals had increased mean pulmonary artery pressure (mPA) and pulmonary vascular resistance (PVR) compared to the controls with no effect on left heart or systemic pressures. RV remodeling and RV dysfunction were also present with a decrease in the RV ejection fraction, increase in the myocardial performance index, impaired longitudinal function, as well as cardiomyocyte hypertrophy, and interstitial fibrosis, which were not present in the controls. Pulmonary vascular remodeling occurred in both embolization models, although only the combination embolization model had a decrease in pulmonary capacitance. Taken together, these cardiopulmonary hemodynamic and structural findings identify the novel combination embolization swine model as a valuable tool for future studies of chronic PH.http://europepmc.org/articles/PMC4414513?pdf=render |
spellingShingle | Jaume Aguero Kiyotake Ishikawa Kenneth M Fish Nadjib Hammoudi Lahouaria Hadri Ana Garcia-Alvarez Borja Ibanez Valentin Fuster Roger J Hajjar Jane A Leopold Combination proximal pulmonary artery coiling and distal embolization induces chronic elevations in pulmonary artery pressure in Swine. PLoS ONE |
title | Combination proximal pulmonary artery coiling and distal embolization induces chronic elevations in pulmonary artery pressure in Swine. |
title_full | Combination proximal pulmonary artery coiling and distal embolization induces chronic elevations in pulmonary artery pressure in Swine. |
title_fullStr | Combination proximal pulmonary artery coiling and distal embolization induces chronic elevations in pulmonary artery pressure in Swine. |
title_full_unstemmed | Combination proximal pulmonary artery coiling and distal embolization induces chronic elevations in pulmonary artery pressure in Swine. |
title_short | Combination proximal pulmonary artery coiling and distal embolization induces chronic elevations in pulmonary artery pressure in Swine. |
title_sort | combination proximal pulmonary artery coiling and distal embolization induces chronic elevations in pulmonary artery pressure in swine |
url | http://europepmc.org/articles/PMC4414513?pdf=render |
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