Inflammation and lung injury in an ovine model of extracorporeal membrane oxygenation support.
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.
Critical Care Research Group, University of Queensland and the Prince Charles Hospital, Brisbane, Australia; M.Passmore@uq.edu.au.
Margaret R
MR
Passmore
Critical Care Research Group, University of Queensland and the Prince Charles Hospital, Brisbane, Australia.|School of Health and Sport Sciences, University of the Sunshine Coast, Sippy Downs, Australia.
Yoke L
YL
Fung
Critical Care Research Group, University of Queensland and the Prince Charles Hospital, Brisbane, Australia.|Research and Development, Australian Red Cross Blood Service, Brisbane, Australia; and.
Gabriela
G
Simonova
Critical Care Research Group, University of Queensland and the Prince Charles Hospital, Brisbane, Australia.
Samuel R
SR
Foley
Critical Care Research Group, University of Queensland and the Prince Charles Hospital, Brisbane, Australia.|Queensland University of Technology, Brisbane, Australia.
Kimble R
KR
Dunster
Critical Care Research Group, University of Queensland and the Prince Charles Hospital, Brisbane, Australia.
Sara D
SD
Diab
Critical Care Research Group, University of Queensland and the Prince Charles Hospital, Brisbane, Australia.|Research and Development, Australian Red Cross Blood Service, Brisbane, Australia; and.
John-Paul
JP
Tung
Critical Care Research Group, University of Queensland and the Prince Charles Hospital, Brisbane, Australia.
Robyn M
RM
Minchinton
Critical Care Research Group, University of Queensland and the Prince Charles Hospital, Brisbane, Australia.
Charles I
CI
McDonald
Critical Care Research Group, University of Queensland and the Prince Charles Hospital, Brisbane, Australia.|Department of Critical Care Medicine, Nambour General Hospital, Nambour, Australia.
Chris M
CM
Anstey
Critical Care Research Group, University of Queensland and the Prince Charles Hospital, Brisbane, Australia.
Kiran
K
Shekar
Critical Care Research Group, University of Queensland and the Prince Charles Hospital, Brisbane, Australia.
John F
JF
Fraser
D055371:Acute Lung Injury / Q000097:blood / Q000150:complications* / Q000201:enzymology / Q000473:pathology*; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D001980:Bronchi / Q000473:pathology; D018893:Bronchoalveolar Lavage; D003187:Compliance; D004487:Edema / Q000150:complications / Q000473:pathology; D004847:Epithelial Cells / Q000201:enzymology / Q000378:metabolism / Q000473:pathology; D015199:Extracorporeal Membrane Oxygenation; D007150:Immunohistochemistry; D053583:Interleukin-1beta / Q000097:blood; D015850:Interleukin-6 / Q000097:blood; D016209:Interleukin-8 / Q000097:blood; D007958:Leukocyte Count; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D009929:Organ Size; D011014:Pneumonia / Q000097:blood / Q000150:complications* / Q000201:enzymology / Q000473:pathology*; D011658:Pulmonary Fibrosis / Q000097:blood / Q000150:complications / Q000378:metabolism / Q000473:pathology; D012756:Sheep; D012907:Smoking / Q000009:adverse effects
D015415:Biomarkers; D053583:Interleukin-1beta; D015850:Interleukin-6; D016209:Interleukin-8; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9
extracorporeal membrane oxygenation; inflammation; lung injury; matrix metalloproteinases