Donor Management in Donation after Brain Death: A Window of Opportunity – Are Pro-Inflammatory Mediators the Target and What is the Effect of Duration of Brain Death?
1Nuffield Department of Surgical Sciences, University of Oxford, Oxford, United Kingdom, 2University of Exeter, Exeter, United Kingdom
Meeting: 2019 American Transplant Congress
Abstract number: B35
Keywords: Brain death, Donation, Inflammation, Tumor necrosis factor (TNF)
Session Name: Poster Session B: Biomarkers, Immune Monitoring and Outcomes
Session Type: Poster Session
Date: Sunday, June 2, 2019
Session Time: 6:00pm-7:00pm
Presentation Time: 6:00pm-7:00pm
Location: Hall C & D
*Purpose: Donation after brain death (BD) is a crucial source of transplanted organs – uncertainty remains how duration of BD contributes to outcomes: This study investigates pro-inflammatory mediator changes from admission to procurement to 1)understand the natural course of secondary neuroimmunological response after BD and 2)identify targets for future intervention.
*Methods: The UK Quality in Organ Donation (QUOD) bioresource was used to select 27 matched brain dead donors with 3 available serum samples from admission to procurement. Individual serum levels of interleukin-6 (IL-6), tumour necrosis factor alpha (TNF-a), complement C5a were measured using ELISA. The results were log-transformed and cumulative average analysis was used for trend detection over time
*Results: We observed distinct temporal changes: IL-6 and C5a show an increase around the diagnosis of BD with subsequently stable levels during donor management (Fig1A, B). TNF-alpha, however, seems to raise just before BD confirmation and falls steadily throughout donor management (Fig1C).
*Conclusions: This is a first description of the temporal trends of pro-inflammatory mediators in BD donors following intracranial haemorrhage. Historically it has been suggested that devastating cerebral injury creates a hostile, pro-inflammatory environment. However, retrospective studies of prolonged BD failed to show inferior abdominal transplant outcomes (Boffa 2017), and in fact reported reduced acute rejection (Martinez-Mier 2016) and a lower risk of delayed graft function (Nijboer 2011). Our work demonstrated different trajectories for IL-6/complement and TNF-alpha during donor management. We were not able to confirm a progressively hostile environment and thus a need to rush and retrieve organs early after brain death. Our previous study of serum markers of donor cerebral injury did not suggest a progressive release of neuronal and glial breakdown products after diagnosis of BD and commencement of donor care (Bera 2018). To complete this work, we now study how anti-inflammatory mediators compare – whether due to a shift towards a cytoprotective environment or due to the administered ‘donor care bundle’. Understanding secondary neuro-immunological trajectories changes after brain death may provide the molecular basis for seemingly paradoxical outcomes after prolonged duration of BD in transplantation. It will also allow us to identify pathways to target during donor management.
To cite this abstract in AMA style:Bera KD, Tabak J, Faro MLLo, Ploeg RJ. Donor Management in Donation after Brain Death: A Window of Opportunity – Are Pro-Inflammatory Mediators the Target and What is the Effect of Duration of Brain Death? [abstract]. Am J Transplant. 2019; 19 (suppl 3). https://atcmeetingabstracts.com/abstract/donor-management-in-donation-after-brain-death-a-window-of-opportunity-are-pro-inflammatory-mediators-the-target-and-what-is-the-effect-of-duration-of-brain-death/. Accessed June 3, 2023.
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