Bootcongres

Kidneys derived from deceased brain dead (DBD) donors have inferior outcomes after transplantation compared to kidneys from living donors. Also, DBD donors suffer from bacterial translocation and endotoxemia. A link between Angiopoietin 1 (Ang1), Angiopoietin 2 (Ang2) and endotoxemia has been established. Ang1 and Ang2 are antagonictic ligands that bind to the Tie2 receptor. We aimed to modify the Ang1 levels in our brain death rat model by administrating vasculotide (VT), a synthetic Tie2 agonist, to clarify whether exogenous administration of VT has a protective role and may be of therapeutical value to improve outcome after DBD transplantation. We administrated 3 µg/kg VT or PBS 30 min before brain death (BD) induction. BD was induced by inflating a subdurally placed balloon catheter in rats. A group of sham operated animals was injected with PBS (n = 7 for all groups). The animals were monitored for 4 hrs. Just before sacrificing the animals blood was collected and lungs and kidneys were harvested for histology and PCR. Plasma levels of ALT, AST, creatinine, LDH and urea were equal in both BD groups. The fold induction of ICAM-1, IL-6 and Tie2 in the kidney and lung is not infuenced by VT administration in the BD groups. Tie2 fold induction of both kidney and lung decreased significantly in the BD+PBS group (mean fold induction kidney 1.1 and lung 0.27) compared to the sham+PBS group (mean fold induction kidney 2.54 and lung 10.83). Functional and inflammatory markers were increased in the BD groups compared to the sham+PBS group and not affected by this dosage of VT. These results show a remarkable effect of brain death on Tie2 fold induction. This reduction suggests a functional role for Tie2 in BD which could not be compensated by administrating VT.