Immunomodulation of brain death-induced lung injury

Judith van Zanden

    Research output: ThesisThesis fully internal (DIV)

    172 Downloads (Pure)

    Abstract

    Lung transplantation is a last-resort treatment for patients with end-stage lung diseases. However unfortunately, a major issue in the field of lung transplantation is donor lung shortage. The process of donor brain death causes inflammation in the donor lung, which leads to lung damage. As a result, only 20-30% of the offered human donor lungs are suitable for transplantation. In this thesis, we investigated ways to modulate this inflammatory process, with the aim to improve donor lung quality. To do so we studied brain death in animal models, which help us understand pathophysiological mechanisms as occur in human donors. First we treated brain-dead rats with methylprednisolone, which successfully dampened lung inflammation after brain death. Thereafter, we tested the potential of treating donor lungs outside the donor body. We developed a so-called ‘ex vivo’ machine for rat lungs, which keeps the lungs ‘breathing’ outside the body by ventilation, and mimics blood flow with nutrient-rich solution. Lungs were effectively treated with methylprednisolone on the ex vivo machine, which offers potential for a targeted way of donor lung treatment, without possible damage to other donor organs. Lastly, we studied involvement of the complement system, part of the innate immune system. We found that complement activation is involved in lung injury after brain death, and we identified potential pathways for future treatment. This thesis shows that optimizing donor lung quality begins in the brain-dead donor, and we believe that dampening inflammation in the potential donor lung will increase the pool of suitable donor lungs.
    Original languageEnglish
    QualificationDoctor of Philosophy
    Awarding Institution
    • University of Groningen
    Supervisors/Advisors
    • Leuvenink, Henri, Supervisor
    • Erasmus, Michiel, Co-supervisor
    • 't Hart, Nils, Co-supervisor
    Award date16-Jun-2021
    Place of Publication[Groningen]
    Publisher
    DOIs
    Publication statusPublished - 2021

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