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Thrombomodulin protects against lung damage created by high level of oxygen with large tidal volume mechanical ventilation in rats
BACKGROUND: Ventilator-induced lung injury (VILI) is associated with inflammatory responses in the lung. Thrombomodulin (TM), a component of the coagulation system, has anticoagulant and anti-inflammatory effects. We hypothesized that the administration of recombinant human soluble TM (rhsTM) would...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2014
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4336269/ https://www.ncbi.nlm.nih.gov/pubmed/25705415 http://dx.doi.org/10.1186/s40560-014-0057-0 |
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author | Iwashita, Yoshiaki Zhang, Erquan Maruyama, Junko Yokochi, Ayumu Yamada, Yasuharu Sawada, Hirofumi Mitani, Yoshihide Imai, Hiroshi Suzuki, Koji Maruyama, Kazuo |
author_facet | Iwashita, Yoshiaki Zhang, Erquan Maruyama, Junko Yokochi, Ayumu Yamada, Yasuharu Sawada, Hirofumi Mitani, Yoshihide Imai, Hiroshi Suzuki, Koji Maruyama, Kazuo |
author_sort | Iwashita, Yoshiaki |
collection | PubMed |
description | BACKGROUND: Ventilator-induced lung injury (VILI) is associated with inflammatory responses in the lung. Thrombomodulin (TM), a component of the coagulation system, has anticoagulant and anti-inflammatory effects. We hypothesized that the administration of recombinant human soluble TM (rhsTM) would block the development of lung injury. METHODS: Lung injury was induced by high tidal volume ventilation for 2 h with 100% oxygen in rats. Rats were ventilated with a tidal volume of 35 ml/kg with pretreatment via a subcutaneous injection of 3 mg/kg rhsTM (HV (high tidal volume)/TM) or saline (HV/SAL) 12 h before mechanical ventilation. Rats ventilated with a tidal volume of 6 ml/kg under 100% oxygen with rhsTM (LV (low tidal volume)/TM) or saline (LV/SAL) were used as controls. Lung protein permeability was determined by Evans blue dye (EBD) extravasation. RESULTS: Lung injury was successfully induced in the HV/SAL group compared with the LV/SAL group, as shown by the significant decrease in arterial oxygen pressure (PaO(2)), increased protein permeability, and increase in mean pulmonary artery pressure (mPAP) and ratio of mean pulmonary artery pressure to mean artery pressure (Pp/Ps). Treatment of rats with lung injury with rhsTM (HV/TM) significantly attenuated the decrease in PaO(2) and the increase in both mPAP and Pp/Ps, which was associated with a decrease in the lung protein permeability. Lung tissue mRNA expressions of interleukin (IL)-1α, IL-1β, IL-6, tumor necrosis factor-α, and macrophage inflammatory protein (MIP)-2 were significantly higher in HV than in LV rats. Rats with VILI treated with rhsTM (HV/TM) had significantly lower mRNA expressions of IL-1α, IL-1β, IL-6, and MIP-2 than those expressions in HV/SAL rats. CONCLUSIONS: Administration of rhsTM may prevent the development of lung injury created by high level of oxygen with large tidal volume mechanical ventilation, which has concomitant decrease in proinflammatory cytokine and chemokine expression in the lung. |
format | Online Article Text |
id | pubmed-4336269 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-43362692015-02-22 Thrombomodulin protects against lung damage created by high level of oxygen with large tidal volume mechanical ventilation in rats Iwashita, Yoshiaki Zhang, Erquan Maruyama, Junko Yokochi, Ayumu Yamada, Yasuharu Sawada, Hirofumi Mitani, Yoshihide Imai, Hiroshi Suzuki, Koji Maruyama, Kazuo J Intensive Care Research BACKGROUND: Ventilator-induced lung injury (VILI) is associated with inflammatory responses in the lung. Thrombomodulin (TM), a component of the coagulation system, has anticoagulant and anti-inflammatory effects. We hypothesized that the administration of recombinant human soluble TM (rhsTM) would block the development of lung injury. METHODS: Lung injury was induced by high tidal volume ventilation for 2 h with 100% oxygen in rats. Rats were ventilated with a tidal volume of 35 ml/kg with pretreatment via a subcutaneous injection of 3 mg/kg rhsTM (HV (high tidal volume)/TM) or saline (HV/SAL) 12 h before mechanical ventilation. Rats ventilated with a tidal volume of 6 ml/kg under 100% oxygen with rhsTM (LV (low tidal volume)/TM) or saline (LV/SAL) were used as controls. Lung protein permeability was determined by Evans blue dye (EBD) extravasation. RESULTS: Lung injury was successfully induced in the HV/SAL group compared with the LV/SAL group, as shown by the significant decrease in arterial oxygen pressure (PaO(2)), increased protein permeability, and increase in mean pulmonary artery pressure (mPAP) and ratio of mean pulmonary artery pressure to mean artery pressure (Pp/Ps). Treatment of rats with lung injury with rhsTM (HV/TM) significantly attenuated the decrease in PaO(2) and the increase in both mPAP and Pp/Ps, which was associated with a decrease in the lung protein permeability. Lung tissue mRNA expressions of interleukin (IL)-1α, IL-1β, IL-6, tumor necrosis factor-α, and macrophage inflammatory protein (MIP)-2 were significantly higher in HV than in LV rats. Rats with VILI treated with rhsTM (HV/TM) had significantly lower mRNA expressions of IL-1α, IL-1β, IL-6, and MIP-2 than those expressions in HV/SAL rats. CONCLUSIONS: Administration of rhsTM may prevent the development of lung injury created by high level of oxygen with large tidal volume mechanical ventilation, which has concomitant decrease in proinflammatory cytokine and chemokine expression in the lung. BioMed Central 2014-10-01 /pmc/articles/PMC4336269/ /pubmed/25705415 http://dx.doi.org/10.1186/s40560-014-0057-0 Text en © Iwashita et al.; licensee BioMed Central Ltd. 2014 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. |
spellingShingle | Research Iwashita, Yoshiaki Zhang, Erquan Maruyama, Junko Yokochi, Ayumu Yamada, Yasuharu Sawada, Hirofumi Mitani, Yoshihide Imai, Hiroshi Suzuki, Koji Maruyama, Kazuo Thrombomodulin protects against lung damage created by high level of oxygen with large tidal volume mechanical ventilation in rats |
title | Thrombomodulin protects against lung damage created by high level of oxygen with large tidal volume mechanical ventilation in rats |
title_full | Thrombomodulin protects against lung damage created by high level of oxygen with large tidal volume mechanical ventilation in rats |
title_fullStr | Thrombomodulin protects against lung damage created by high level of oxygen with large tidal volume mechanical ventilation in rats |
title_full_unstemmed | Thrombomodulin protects against lung damage created by high level of oxygen with large tidal volume mechanical ventilation in rats |
title_short | Thrombomodulin protects against lung damage created by high level of oxygen with large tidal volume mechanical ventilation in rats |
title_sort | thrombomodulin protects against lung damage created by high level of oxygen with large tidal volume mechanical ventilation in rats |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4336269/ https://www.ncbi.nlm.nih.gov/pubmed/25705415 http://dx.doi.org/10.1186/s40560-014-0057-0 |
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