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A novel modified Steen solution limits inflammatory processes during ex vivo lung perfusion and improves graft function post-transplantation

Lookup NU author(s): Dr Jenny GilmourORCiD, Professor Andrew FisherORCiD, Professor Simi AliORCiD

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

Abstract

© 2024. Background: Ex vivo lung perfusion allows donor lung preservation, assessment, and reconditioning before transplantation, but is associated with increased inflammatory injury over time. Addition of antioxidative and anti-inflammatory agents to perfusate formulations could limit iatrogenic injury during perfusion. The effectiveness of a modified Steen solution containing acetyl salicylic acid, retinoic acid, and methylprednisolone was examined using a porcine extended criteria donor ex vivo lung perfusion and transplantation model. Methods: Porcine donor lungs underwent 24 hours cold storage and were then randomized to 4 hours normothermic ex vivo lung perfusion with modified Steen or original Steen, followed by single lung transplantation into a recipient pig. RNA-sequencing was used to assess tissue inflammatory changes during perfusion. Organ function was examined during perfusion and following transplantation and compared between groups. Results: Lungs perfused with modified Steen showed reduced pulmonary vascular resistance (p = 0.0391) and stable pulmonary artery pressure despite achieving higher flows (p = 0.0001) compared to Steen. Lung tissue showed negative enrichment of the tumor necrosis factor-α (TNF-α) signaling via nuclear factor-κB (NF-κB) pathway (p = 0.0040) in modified Steen compared to Steen. Recipients of lungs perfused with modified Steen also showed improved post-transplantation oxygenation (p = 0.0462). Conclusions: This study highlights the superiority of modified Steen compared with original Steen. The modifications to Steen solution appear to limit inflammatory injury via the NF-κB signaling pathway during perfusion, leading to improved post-transplant function. Modified Steen provides the potential to improve post-transplant outcomes following ex vivo lung perfusion of extended criteria lungs and could also facilitate extended assessment and preservation, as well as administration of advanced therapies.

Publication metadata

Author(s): Gilmour J, Sigvardsson A-L, Henriksson E, Fisher AJ, Ali S

Publication type: Article

Publication status: Published

Journal: JHLT Open

Year: 2024

Volume: 4

Print publication date: 01/05/2025

Online publication date: 02/04/2024

Acceptance date: 02/04/2018

Date deposited: 29/07/2025

ISSN (electronic): 2950-1334

Publisher: Elsevier BV

URL: https://doi.org/10.1016/j.jhlto.2024.100091

DOI: 10.1016/j.jhlto.2024.100091

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