Research Group

  • Dr Johannes Lisman, Principal Investigator
  • Prof. Dr Robert J. Porte, Co-Investigator
  • Prof. Dr Rutger J. Ploeg, Research Associate

Location

  • University Medical Centre Groningen, Groningen, The Netherlands

Title

  • Do Blood Platelets Affect Quality of Organs to be Transplanted from a Brain-Dead Organ Donor?

Organ transplantation is a life-saving treatment for patients with end-stage kidney, liver, or lung disease. The vast majority of transplanted organs are retrieved from brain-dead organ donors. However, organs retrieved from brain-dead donors function much worse as compared to organs retrieved from living donors. This implicates that brain death results in damage to organs, but the mechanisms responsible for this are incompletely known. It has been established that brain death results in induction of a pro-inflammatory state in the donor. This inflammatory state is accompanied by activation of endothelial cells, which express adhesion molecules, and release contents of their intracellular granules. This project aims to investigate whether part of the organ damage in the brain-dead organ donor can be explained by adhesion of blood platelets to the activated endothelium. In the first set of experiments, an animal model of brain death will be used. Brain death will be induced in rats, and the quality of selected organs (kidney and liver) will be assessed by ex vivo experiments, or by transplanting these organs into recipient rats. The role of platelets will be assessed by administration of various platelet-inhibitory drugs to the brain-dead animal. Also, endothelial activation will be exaggerated by administration of DDAVP, which is frequently used in the brain-dead donor as an anti-diuretic, but results in endothelial cell activation as a side effect. In the second approach, we will measure markers of platelet activations in plasma samples retrieved from human brain-death donors to see if elevated platelet activation is correlated with poorer prognosis (graft functioning and graft survival). The results of this study will teach us whether quality of organs used for transplantation can be improved by prevention of platelet adhesion to the activated graft endothelium. This prevention of platelet-graft interaction may be accomplished by administration of established anti-platelet drugs to the brain-dead donor.

Final Report