Inflammation and lung injury in an ovine model of extracorporeal membrane oxygenation support

Passmore, Margaret R., Fung, Yoke L., Simonova, Gabriela, Foley, Samuel R., Dunster, Kimble R., Diab, Sara D., Tung, John-Paul, Minchinton, Robyn M., McDonald, Charles I., Anstey, Chris M., Shekar, Kiran and Fraser, John F. (2016) Inflammation and lung injury in an ovine model of extracorporeal membrane oxygenation support. AJP - Lung Cellular and Molecular Physiology, 311 6: L1202-L1212. doi:10.1152/ajplung.00296.2016


Author Passmore, Margaret R.
Fung, Yoke L.
Simonova, Gabriela
Foley, Samuel R.
Dunster, Kimble R.
Diab, Sara D.
Tung, John-Paul
Minchinton, Robyn M.
McDonald, Charles I.
Anstey, Chris M.
Shekar, Kiran
Fraser, John F.
Title Inflammation and lung injury in an ovine model of extracorporeal membrane oxygenation support
Journal name AJP - Lung Cellular and Molecular Physiology   Check publisher's open access policy
ISSN 1522-1504
1040-0605
Publication date 2016-12-12
Sub-type Article (original research)
DOI 10.1152/ajplung.00296.2016
Open Access Status Not yet assessed
Volume 311
Issue 6
Start page L1202
End page L1212
Total pages 11
Place of publication Bethesda, MD, United States
Publisher American Physiological Society
Language eng
Abstract Extracorporeal membrane oxygenation (ECMO) is a life-saving treatment for patients with severe refractory cardiorespiratory failure. Exposure to the ECMO circuit is thought to trigger/exacerbate inflammation. Determining whether inflammation is the result of the patients’ underlying pathologies or the ECMO circuit is difficult. To discern how different insults contribute to the inflammatory response, we developed an ovine model of lung injury and ECMO to investigate the impact of smoke-induced lung injury and ECMO in isolation and cumulatively on pulmonary and circulating inflammatory cells, cytokines, and tissue remodeling. Sheep receiving either smoke-induced acute lung injury (S-ALI) or sham injury were placed on veno-venous (VV) ECMO lasting either 2 or 24 h, with controls receiving conventional ventilation only. Lung tissue, bronchoalveolar fluid, and plasma were analyzed by RT-PCR, immunohistochemical staining, and zymography to assess inflammatory cells, cytokines, and matrix metalloproteinases. Pulmonary compliance decreased in sheep with S-ALI placed on ECMO with increased numbers of infiltrating neutrophils, monocytes, and alveolar macrophages compared with controls. Infiltration of neutrophils was also observed with S-ALI alone. RT-PCR studies showed higher expression of matrix metalloproteinases 2 and 9 in S-ALI plus ECMO, whereas IL-6 was elevated at 2 h. Zymography revealed higher levels of matrix metalloproteinase 2. Circulating plasma levels of IL-6 were elevated 1–2 h after commencement of ECMO alone. These data show that the inflammatory response is enhanced when a host with preexisting pulmonary injury is placed on ECMO, with increased infiltration of neutrophils and macrophages, the release of inflammatory cytokines, and upregulation of matrix metalloproteinases.
Keyword Extracorporeal membrane oxygenation
Inflammation
Lung injury
Matrix metalloproteinases
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
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