Bootcongres

Brain death (BD) retrieved donor organs have been the main source of organs for liver transplantation. However, BD negatively affects organ quality resulting in impaired graft function and patient outcome when compared to living donation. BD induced ischemia causes the central nervous system to malfunction, resulting in hemodynamic instability, hormonal impairment and a cascade of inflammatory events resulting in poorer transplantation outcomes. Plasma levels of free triiodothyronine (T3) and free thyroxine (T4) progressively fall to 50% of baseline levels within one hour after BD and become undetectable after 10 hours. Pre-conditioning with thyroid hormone has shown protective effects in liver ischemia reperfusion injury and regeneration. To determine the preconditioning effects of thyroid hormones, we evaluated cellular injury, apoptotic and regenerative effects and inflammatory markers after pre-treatment with T3 in brain dead rats. T3 (0.1 mg/kg) or vehicle were administered intraperitoneally 2 hours prior to BD induction. BD was induced by inflating a 4.0 Fogarty catheter in the epidural space. Animals were kept hemodynamically stable for 4 hours after which organs were harvested. Gene and protein expression was measured with real-time reverse transcriptase–polymerase chain reaction and immunohistochemistry. T3 administration significantly reduced plasma AST levels (p < 0.05) and reduced ALT levels in brain dead animals. BD resulted in an increased gene expression of IL-6, MCP-1 and IL-1β and a decreased expression of TNF-α, which was not altered by T3 –administration. BAX mRNA expression did not change following BD nor after pre-treatment with T3. Bcl-2 decreased following BD but was not affected by T3 administration. The BAX/Bcl-2 ratio increased in brain dead animals and decreased significantly after T3-treatment. Caspase-3 was also significantly reduced after T3-treatment. Based on our data, T3 displays protective preconditioning effects in the liver of brain dead rats resulting in decreased liver injury and cellular apoptosis. This protective effects are not related with anti-inflammatory changes of T3-treatment. T3 preconditioning effects could directly trigger cellular protective pathways. Further research will need to be performed to gain insight into the protective effects of T3 preconditioning.