Poster Presentation International Veterinary Immunology Symposium 2016

Inflammation and Lung Remodelling in an Ovine Model of Extracorporeal Membrane Oxygenation Support (#164)

Margaret Passmore 1 , Yoke Lin Fung 1 , Samuel Foley 1 , Gabriela Simonova 1 2 , Kimble Dunster 1 , Sara Diab 1 , John-Paul Tung 1 2 , Robyn Minchinton 1 , Charles McDonald 1 , Chris Anstey 1 , Kiran Shekar 1 , John Fraser 1
  1. Critical Care Research Group, The Prince Charles Hospital and the University of Queensland, Chermside, QLD, Australia
  2. Australian Red Cross Blood Service, Kelvin Grove, QUEENSLAND, Australia

Rationale: 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; however, delineating the effect of the ECMO circuit from that of the patient’s underlying pathologies is difficult in clinical studies. Therefore, we developed an ovine model to investigate the impact of smoke-induced acute lung injury (S-ALI) and ECMO both individually and cumulatively on pulmonary and circulating inflammatory cells, cytokines and tissue remodelling.

Methods: Sheep received either S-ALI (n=23) or sham injury (n=20). Veno-venous (VV) ECMO commenced 2hrs later, lasting 2hrs (n=8) or 24hrs (n=8).  The control group was not placed on ECMO, receiving smoke injury only (n=7). A second group (n=16) was placed on ECMO without S-ALI for 2hrs (n=8) and 24hrs (n=8) while the healthy controls received ventilation only for 24 hours (n=4). Lung tissue, bronchoalveolar fluid and plasma were analysed by RT-PCR, immunohistochemical staining and zymography to assess inflammatory cells, cytokines and matrix metalloproteinases.

Results: Pulmonary compliance decreased in sheep with S-ALI placed on ECMO with increased numbers of infiltrating macrophages compared to controls. Infiltration of neutrophils was also observed with S-ALI alone. RT-PCR studies showed higher expression of MMP2 and MMP9 in S-ALI plus ECMO while IL-6 was elevated at 2hrs. Zymography revealed higher levels of MMP2. Circulating plasma levels of IL-6 were elevated 1-2hrs after commencement of ECMO alone.

Conclusions: The inflammatory response is enhanced when a host with pre-existing pulmonary injury is placed on ECMO with increased infiltration of neutrophils and macrophages, the release of inflammatory cytokines and up-regulation of matrix metalloproteinases. Future research will focus on minimising the inflammatory, hematologic and coagulation perturbations that may arise in the context of ECMO therapy.