Brain dead donor graft deterioration and attenuation with N-octanoyl dopamine preconditioning: Emphasis on lung and kidney grafts

Christina Maximilia Valentina Hottenrott

    Research output: ThesisThesis fully internal (DIV)

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    The success of transplantation is limited by the availability of donor organs and graft survival, which depend on the immune activation in the brain dead donor. In the first part of this thesis the salutary effect of the preconditioning agent N-octanoyl dopamine (NOD) is elucidated in transplantation associated processes. In the second part the effect of ventilation and etiology of brain death on the donor lung and kidney are described.
    Firstly, NOD preconditioning resulted in improved kidney function in an acute kidney injury model after the insult and improved recovery compared to saline treatment. Correspondingly, NOD prevented cell injury in cold preserved cardiomyocytes and was accompanied by a faster metabolic recovery, survival and functionality after preservation. Additionally, NOD limited the immune response in endothelial cells and the adhesion of proinflammatory cells.
    Secondly, a lung protective ventilation strategy resulted in an improved survival compared to a traditional ventilation strategy. Traditional ventilation caused pronounced lung injury and inflammation in brain death compared to non-brain death. In the kidneys the effect of brain death was more pronounced than the effect of ventilation alone. Thirdly, different etiology of brain death did not cause a difference in inflammation in the lungs. However, fast brain death induction resulted in increased lung injury. In contrast, slow induction led to a deterioration of kidney function and led to an increased inflammation and oxidative stress in the parenchyma. While in the liver no functional change was found inflammation and cell death were increased.
    Original languageEnglish
    QualificationDoctor of Philosophy
    Awarding Institution
    • University of Groningen
    • Leuvenink, Henri, Supervisor
    • Yard, Benito A., Supervisor, External person
    • Mariani, Massimo, Supervisor
    • Erasmus, Michiel, Co-supervisor
    Award date13-Jan-2016
    Place of Publication[Groningen]
    Print ISBNs978-90-367-8589-1
    Electronic ISBNs978-90-367-8588-4
    Publication statusPublished - 2016

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