• J. Thorac. Cardiovasc. Surg. · Dec 2023

    Identification of regional variation in gene expression and inflammatory proteins in donor lung tissue and ex vivo lung perfusate.

    • Bonnie T Chao, Andrew T Sage, Jonathan C Yeung, Xiaohui Bai, Jin Ma, Tereza Martinu, Mingyao Liu, Marcelo Cypel, Dirk Van Raemdonck, Laurens J Ceulemans, Arne Neyrinck, Stijn Verleden, and Shaf Keshavjee.
    • Toronto Lung Transplant Program and Latner Thoracic Research Laboratories, Toronto General Hospital Research Institute, University Health Network, Toronto, Ontario, Canada; Institute of Biomedical Engineering, University of Toronto, Toronto, Ontario, Canada.
    • J. Thorac. Cardiovasc. Surg. 2023 Dec 1; 166 (6): 15201528.e31520-1528.e3.

    ObjectiveDiagnosing lung injury is a challenge in lung transplantation. It has been unclear if a single biopsy specimen is truly representative of the entire organ. Our objective was to investigate lung inflammatory biomarkers using human lung tissue biopsies and ex vivo lung perfusion perfusate.MethodsEight human donor lungs declined for transplantation were air inflated, flash frozen, and partitioned from apex to base. Biopsies were then sampled throughout the lung. Perfusate was sampled from 4 lung lobes in 8 additional donor lungs subjected to ex vivo lung perfusion. The levels of interleukin-6, interleukin-8, interleukin-10, and interleukin-1β were measured using quantitative reverse transcription polymerase chain reaction from lung biopsies and enzyme-linked immunosorbent assay from ex vivo lung perfusion perfusate.ResultsThe median intra-biopsy equal-variance P value was .50 for messenger RNA biomarkers in tissue biopsies. The median intra-biopsy coefficient of variance was 18%. In donors with no apparent focal injuries, the biopsies in each donor showed no difference in various lung slices, with a coefficient of variance of 20%. The exception was biopsies from the lingula and injured focal areas that demonstrated larger differences. Cytokines in ex vivo lung perfusion perfusate showed minimal variation among different lobes (coefficient of variance = 4.9%).ConclusionsCytokine gene expression in lung biopsies was consistent, and the biopsy analysis reflects the whole lung, except when specimens were collected from the lingula or an area of focal injury. Ex vivo lung perfusion perfusate also provides a representative measurement of lung inflammation from the draining lobe. These results will reassure clinicians that a lung biopsy or an ex vivo lung perfusion perfusate sample can be used to inform donor lung selection.Copyright © 2023. Published by Elsevier Inc.

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