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Excerpt
Primary and chronic transplant dysfunction remain major complications after transplantation, primarily induced by immunological events during and after the transplant process. A difference in short and long term function is consistently shown in kidney transplant studies between L(U)RD and cadaveric donor organs. We hypothesize that this is caused by increased immunogenicity due to brain death in the cadaver - in contrast to the living-donor predisposing for ischemia/reperfusion injury. In this experiment we studied short (1h) and long-term (6h) effects of brain death on liver function and immunogenicity in both hypotensive and normotensive donors. Organ dysfunction was assessed by standard serum parameters and immunogenicity by staining for ICAM-1, VCAM-1, CD45, TcR, CD8, CD4, PMN, NKcells, MΦ. Healthy sham operated rats served as controls. After induction of brain death all rats became hypotensive. Hemodynamic support was only administered in one group to obtain normotension. At time of sacrifice serum was sampled and liver tissue was harvested and snap frozen in isopenthane. AST and LDH serum concentrations reflecting dysfunction of the liver prior to organ harvesting was most significant in marginal donors and diminished with normotension vs. levels in controls. Irrespective of hemodynamic status 1 h after induction of brain death immunocytochemical staining showed progressive ICAM-1 and VCAM-1 staining facilitating leukocyte recruitment not seen in controls. This was associated with significant increased amounts of infiltrating leukocytes into the parenchyma, primarily of PMN's. In addition, a significant increase in the amount of macrophages was found in brain dead rats. (Table)
This study indicates that brain death induces a non-specific immune response leading to an increased immunogenicity of the donor liver that cannot be counteracted by conventional donor management. The immunogenetic activation potentially increases the risk on primary and chronic transplant dysfunction of cadaver liver grafts. Therefore, brain death should no longer be considered a static and given condition, but an alarming pathophysiological state during which cytoprotective intervention is required.
