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Profiling inflammation and tissue injury markers in perfusate and bronchoalveolar lavage fluid during human ex vivo lung perfusion

Lookup NU author(s): Anders Andreasson, Danai Karamanou, Dr Colin GillespieORCiD, Kasim Jiwa, Dr Nicola Green, Dr Lee Borthwick, Stephen Clark, Professor Simi Ali, Professor John Dark, Professor Andrew FisherORCiD

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This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License (CC BY-NC 4.0).


Abstract

© The Author 2016. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved. Objectives: Availability of donor lungs suitable for transplant falls short of current demand and contributes to waiting list mortality. Ex vivo lung perfusion (EVLP) offers the opportunity to objectively assess and recondition organs unsuitable for immediate transplant. Identifying robust biomarkers that can stratify donor lungs during EVLP to use or non-use or for specific interventions could further improve its clinical impact. METHODS: In this pilot study, 16 consecutive donor lungs unsuitable for immediate transplant were assessed by EVLP. Key inflammatory mediators and tissue injury markers were measured in serial perfusate samples collected hourly and in bronchoalveolar lavage fluid (BALF) collected before and after EVLP. Levels were compared between donor lungs that met criteria for transplant and those that did not. RESULTS: Seven of the 16 donor lungs (44%) improved during EVLP and were transplanted with uniformly good outcomes. Tissue and vascular injury markers lactate dehydrogenase, HMGB-1 and Syndecan-1 were significantly lower in perfusate from transplanted lungs. A model combining IL-1b and IL-8 concentrations in perfusate could predict final EVLP outcome after 2 h assessment. In addition, perfusate IL-1b concentrations showed an inverse correlation to recipient oxygenation 24 h post-transplant. CONCLUSIONS: This study confirms the feasibility of using inflammation and tissue injury markers in perfusate and BALF to identify donor lungs most likely to improve for successful transplant during clinical EVLP. These results support examining this issue in a larger study.


Publication metadata

Author(s): Andreasson ASI, Karamanou DM, Gillespie CS, Özalp F, Butt T, Hill P, Jiwa K, RWalden H, Green NJ, Borthwick LA, Clark SC, Pauli H, Gould KF, Corris PA, Ali S, Dark JH, Fisher AJ

Publication type: Article

Publication status: Published

Journal: European Journal of Cardio-thoracic Surgery

Year: 2017

Volume: 51

Issue: 3

Pages: 577-586

Online publication date: 07/12/2016

Acceptance date: 12/08/2016

Date deposited: 24/10/2017

ISSN (print): 1010-7940

ISSN (electronic): 1873-734X

Publisher: European Association for Cardio-Thoracic Surgery

URL: https://doi.org/10.1093/ejcts/ezw358

DOI: 10.1093/ejcts/ezw358


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