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

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.

Cardiorespiratory physiological perturbations after acute smoke-induced lung injury and during extracorporeal membrane oxygenation support in sheep

“…A further limitation is that cytokine levels, as predictors of lung injury, were not quantified. Using ELISA assays to quantify cytokine levels proved difficult and the cost was prohibitive in the present study, although subsequent efforts were made by a few members of the original research group in this regard 5 . It is partially for this reason that pioneering studies 16 have been proposed for the development of proteogenomic assays as an alternative to ELISA-to learn from circulating markers of acute inflammation in injured sheep used as models of intensive care, to understand critical illness.…”

“…The source of data for this study was from a sheep model 2 – 5 in which sheep were treated for acute smoke-induced acute lung injury using veno-venous (VV) extracorporeal membrane oxygenation (ECMO) 2 , a form of extracorporeal life support (ECLS) developed to complement the treatment of acute lung injury in humans 6 – 8 . During this type of ECLS, venous blood is carried from the patient to a gas exchange device where the blood is enriched with oxygen, has carbon dioxide is removed, and oxygenated blood is returned to the patient’s circulation in the right atrium.…”

Cardiorespiratory physiological perturbations after acute smoke-induced lung injury and during extracorporeal membrane oxygenation support in sheep

“…Data were initially available in abstract form and subsequently as a full publication on inflammatory cell infiltration into the lung tissue with a trend toward increased lung injury in sheep that inhaled smoke, revealing damage to the bronchiolar lining and infiltration of inflammatory cells 5,[21][22][23] .…”

“…A further limitation is that cytokine levels, as predictors of lung injury, were not quantified. Using ELISA assays to quantify cytokine levels proved difficult and the cost was prohibitive in the present study, although subsequent efforts were made by a few members of the original research group in this regard 5 . It is partially for this reason that pioneering studies 16 On another note, it can be argued that sheep ECMO data is already out there however, cardiac function and haemodynamic data has not been reported in sufficient detail in the manner that this study has.…”

“…Information Classification: General ratio in sheep studies 5,9,22 , the understanding of ECMO in respiratory life-support in human medicine continues to grow in a positive direction overall; moreover, there is evidence that it is useful as a lifesaving treatment. These novel observations from sheep could help in understanding similar pathology such as that which occurs in animal victims of smoke inhalation from house or bush fires, aspiration pneumonia secondary to tick paralysis, and in the management of COVID-19 in humans [54][55][56] .…”