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

Authors :
Mittendorfer M
Pierre L
Huzevka T
Schofield J
Abrams ST
Wang G
Toh CH
Bèchet NB
Caprnja I
Kjellberg G
Aswani A
Olm F
Lindstedt S
Source :
The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation [J Heart Lung Transplant] 2024 Jul 20. Date of Electronic Publication: 2024 Jul 20.
Publication Year :
2024
Publisher :
Ahead of Print

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).<br />Methods: 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 (nontreated) (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.<br />Results: After EVLP and NET removal in porcine lungs, PaO <subscript>2</subscript> /FiO <subscript>2</subscript> 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 (p= 0.0260) than nontreated lungs. According to histopathology, treated lungs showed less immune cell infiltration and less edema compared with nontreated lungs, which was reflected in decreased levels of proinflammatory cytokines in EVLP perfusate and bronchoalveolar lavage fluid.<br />Conclusions: 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.<br /> (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Details

Language :
English
ISSN :
1557-3117
Database :
MEDLINE
Journal :
The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation
Publication Type :
Academic Journal
Accession number :
39038563
Full Text :
https://doi.org/10.1016/j.healun.2024.07.007