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Restoring discarded porcine lungs by ex vivo removal of neutrophil extracellular traps

Mittendorfer, Margareta LU ; Pierre, Leif LU ; Huzevka, Tibor LU ; Schofield, Jeremy ; Abrams, Simon T ; Wang, Guozheng ; Toh, Cheng-Hock ; Bechet, Nicholas B LU ; Caprnja, Ilma and Kjellberg, Gunilla , et al. (2024) In The Journal of Heart and Lung Transplantation
Abstract

BACKGROUND: By causing inflammation and tissue damage, neutrophil extracellular traps (NETs) constitute an underlying mechanism of aspiration-induced lung injury, a major factor of the low utilization of donor lungs in lung transplantation (LTx).

METHOD: To determine whether NET removal during ex vivo lung perfusion (EVLP) can restore lung function and morphology in aspiration-damaged lungs, gastric aspiration lung injury was induced in 12 pigs. After confirmation of acute respiratory distress syndrome, the lungs were explanted and assigned to NET removal connected to EVLP (treated) (n=6) or EVLP only (non-treated) (n=6). Hemodynamic measurements were taken, and blood and tissue samples were collected to assess lung function,... (More)

BACKGROUND: By causing inflammation and tissue damage, neutrophil extracellular traps (NETs) constitute an underlying mechanism of aspiration-induced lung injury, a major factor of the low utilization of donor lungs in lung transplantation (LTx).

METHOD: To determine whether NET removal during ex vivo lung perfusion (EVLP) can restore lung function and morphology in aspiration-damaged lungs, gastric aspiration lung injury was induced in 12 pigs. After confirmation of acute respiratory distress syndrome, the lungs were explanted and assigned to NET removal connected to EVLP (treated) (n=6) or EVLP only (non-treated) (n=6). Hemodynamic measurements were taken, and blood and tissue samples were collected to assess lung function, morphology, levels of cell-free DNA, extracellular histones, and nucleosomes as markers of NETs as well as cytokine levels.

RESULTS: After EVLP and NET removal in porcine lungs, PaO
2/FiO
2 ratios increased significantly compared to those undergoing EVLP alone (p=0.0411). Treated lungs had lower cell-free DNA (p=0.0260) and lower levels of extracellular histones in EVLP perfusate than non-treated lungs (p=0.0260). According to histopathology, treated lungs showed less immune cell infiltration and less oedema compared with non-treated lungs which was reflected in decreased levels of pro-inflammatory cytokines in EVLP perfusate and BALF.

CONCLUSION: To conclude, removing NETs during EVLP improved lung function and morphology in aspiration-damaged donor lungs. The ability to remove NETs during EVLP could represent a new therapeutic approach for LTx and potentially expand the donor pool for transplantation.

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Contribution to journal
publication status
epub
subject
in
The Journal of Heart and Lung Transplantation
publisher
Elsevier
external identifiers
  • scopus:85200361864
  • pmid:39038563
ISSN
1557-3117
DOI
10.1016/j.healun.2024.07.007
language
English
LU publication?
yes
id
70ec90b9-c23d-421e-a496-d8f75bba71ea
date added to LUP
2024-07-26 10:26:58
date last changed
2024-11-04 14:20:52
@article{70ec90b9-c23d-421e-a496-d8f75bba71ea,
  abstract     = {{<p>BACKGROUND: By causing inflammation and tissue damage, neutrophil extracellular traps (NETs) constitute an underlying mechanism of aspiration-induced lung injury, a major factor of the low utilization of donor lungs in lung transplantation (LTx).</p><p>METHOD: To determine whether NET removal during ex vivo lung perfusion (EVLP) can restore lung function and morphology in aspiration-damaged lungs, gastric aspiration lung injury was induced in 12 pigs. After confirmation of acute respiratory distress syndrome, the lungs were explanted and assigned to NET removal connected to EVLP (treated) (n=6) or EVLP only (non-treated) (n=6). Hemodynamic measurements were taken, and blood and tissue samples were collected to assess lung function, morphology, levels of cell-free DNA, extracellular histones, and nucleosomes as markers of NETs as well as cytokine levels.</p><p>RESULTS: After EVLP and NET removal in porcine lungs, PaO<br>
 2/FiO<br>
 2 ratios increased significantly compared to those undergoing EVLP alone (p=0.0411). Treated lungs had lower cell-free DNA (p=0.0260) and lower levels of extracellular histones in EVLP perfusate than non-treated lungs (p=0.0260). According to histopathology, treated lungs showed less immune cell infiltration and less oedema compared with non-treated lungs which was reflected in decreased levels of pro-inflammatory cytokines in EVLP perfusate and BALF.<br>
 </p><p>CONCLUSION: To conclude, removing NETs during EVLP improved lung function and morphology in aspiration-damaged donor lungs. The ability to remove NETs during EVLP could represent a new therapeutic approach for LTx and potentially expand the donor pool for transplantation.</p>}},
  author       = {{Mittendorfer, Margareta and Pierre, Leif and Huzevka, Tibor and Schofield, Jeremy and Abrams, Simon T and Wang, Guozheng and Toh, Cheng-Hock and Bechet, Nicholas B and Caprnja, Ilma and Kjellberg, Gunilla and Aswani, Andrew and Olm, Franziska and Lindstedt, Sandra}},
  issn         = {{1557-3117}},
  language     = {{eng}},
  month        = {{07}},
  publisher    = {{Elsevier}},
  series       = {{The Journal of Heart and Lung Transplantation}},
  title        = {{Restoring discarded porcine lungs by ex vivo removal of neutrophil extracellular traps}},
  url          = {{http://dx.doi.org/10.1016/j.healun.2024.07.007}},
  doi          = {{10.1016/j.healun.2024.07.007}},
  year         = {{2024}},
}