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A Split-Lung Ex Vivo Perfusion Model for Time- and Cost-Effective Evaluation of Therapeutic Interventions to the Human Donor Lung

Lookup NU author(s): Nick Chilvers, Dr Jenny Gilmour, Marnie BrownORCiD, Lucy BatesORCiD, Chong Pang, Professor John Dark, Professor Andrew FisherORCiD

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


Abstract

Copyright © 2024 Chilvers, Gilmour, Brown, Bates, Pang, Pauli, Dark and Fisher.With the ongoing shortage of donor lungs, ex vivo lung perfusion (EVLP) offers the opportunity for objective assessment and potential therapeutic repair of marginal organs. There is a need for robust research on EVLP interventions to increase the number of transplantable organs. The use of human lungs, which have been declined for transplant, for these studies is preferable to animal organs and is indeed essential if clinical translation is to be achieved. However, experimental human EVLP is time-consuming and expensive, limiting the rate at which promising interventions can be assessed. A split-lung EVLP model, which allows stable perfusion and ventilation of two single lungs from the same donor, offers advantages scientifically, financially and in time to yield results. Identical parallel circuits allow one to receive an intervention and the other to act as a control, removing inter-donor variation between study groups. Continuous hemodynamic and airway parameters are recorded and blood gas, perfusate, and tissue sampling are facilitated. Pulmonary edema is assessed directly using ultrasound, and indirectly using the lung tissue wet:dry ratio. Evans blue dye leaks into the tissue and can quantify vascular endothelial permeability. The split-lung ex vivo perfusion model offers a cost-effective, reliable platform for testing therapeutic interventions with relatively small sample sizes.


Publication metadata

Author(s): Chilvers NJS, Gilmour J, Brown ML, Bates L, Pang CY, Pauli H, Dark J, Fisher AJ

Publication type: Article

Publication status: Published

Journal: Transplant International

Year: 2024

Volume: 37

Online publication date: 28/02/2024

Acceptance date: 12/02/2024

Date deposited: 25/03/2024

ISSN (print): 0934-0874

ISSN (electronic): 1432-2277

Publisher: Frontiers

URL: https://doi.org/10.3389/ti.2024.12573

DOI: 10.3389/ti.2024.12573

Data Access Statement: The raw data supporting the conclusion of this article will be made available by the authors, without undue reservation.

PubMed id: 38481465


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Funding

Funder referenceFunder name
National Institute for Health and Care Research (NIHR) Blood and Transplant Research Unit in Organ Donation and Transplantation (NIHR203332)
Wellcome 4ward North Clinical training fellowship (R127002)

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