Induction of organ dysfunction and up-regulation of inflammatory markers in the liver and kidneys of hypotensive brain dead rats: A model to study marginal organ donors

Background. Marginal donors exposed to the full array of effects induced by brain death are characterized by low success rates after transplantation. This study examined whether organs from marginal brain dead animals show an y change in organ function or tissue activation making them eventually more susceptible for additional damage during preservation and transplantation. Methods. To study this hypothesis we first focused on effects of brain deat h on donor organ quality by using a brain death model in the rat. After ind uction of brain death, Wistar rats were ventilated for 1 and 6 hr and then killed. Sham-operated rats served as controls. Organ function was studied u sing standard serum parameters. Tissue activation of liver and kidney was a ssessed by staining of immediate early gene products (IEG: FOS, JUN), and i nflammatory markers; cell adhesion molecules (Intercellular adhesion molecu le-1, vascular cell adhesion molecule-1), leukocyte infiltrates (CD45, T ce ll receptor, CD8, CD4), and MHC class II. Results. During brain death progressive organ dysfunction was observed that coincided with a significant increase in activation of immediate early gen es, intercellular adhesion molecule-1, vascular cell adhesion molecule-1, C D45, and MHC class II versus non-brain dead controls. In liver tissue also the markers for T cell receptor and CD8 significantly increased. Conclusions. These findings suggest that an immune activation with increase d endothelial cell activation and immediate early gene expression occurs in marginal donors after brain death induction. We suggest that brain death s hould not longer be regarded as a given nondeleterious condition but as a d ynamic process with potential detrimental effects on donor organs that coul d predispose grafts for increased alloreactivity after transplantation.