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The alloantigen-independent factors brain death and cold ischemia: prospects for a better graft survival through different donor management concepts

(2009) Höger, Simone

Brain death and cold ischemia both worsen graft outcome after transplantation. The experimental studies presented in this thesis were aimed to elucidate the influence of brain death and cold storage on organ quality and to develop new donor management strategies.
Animal models were used to show that brain death induced inflammation correlates with autonomic neurological dysfunction. Vagus nerve stimulation can attenuate the pro-inflammatory state of organs in brain-dead donors. Brain death amplifies tissue damage when renal allografts are subsequently subjected to prolonged cold ischemia. Because catecholamines are frequently used on the intensive care unit, we investigated if catecholamines, in particular dopamine, influence the pro-inflammatory state of brain death and if this translates in a better graft outcome after transplantation. Indeed we have shown that dopamine treatment reduces the inflammatory response in renal allografts of brain dead donors and that this is independent of blood pressure stabilisation. The beneficial effect of donor dopamine treatment translates in better early renal function and less inflammation after transplantation.
When brain death was not installed, donor dopamine treatment was also beneficial in a model of acute rejection in combination with prolonged cold ischemia. It significantly reduced the severity of acute rejection. Apart from dopamine treatment we also studied the effect of carbon monoxide (CO) on vascular remodelling and function of aorta grafts that were subjected to cold preservation. The addition of CO- releasing molecules, i.e. CORM-3, significantly improved vascular function after cold preservation and inhibited intima hyperplasia in an aorta transplantation model.

	Title and contents
	Chapter 1
	Chapter 2
	Chapter 3
	Chapter 4
	Chapter 5
	Chapter 6
	Chapter 7
	General discussion, Summary
	Acknowledgments
	List of publications
	Complete thesis