title: Impact of brain death on ischemia/reperfusion injury in liver transplantation.
abstract: OBJECTIVE
  In liver transplantation, the ischemia/reperfusion injury (IRI) is influenced by factors related to graft quality, organ procurement and the transplant procedure itself. However, in brain-dead donors, the process of death itself also thoroughly affects organ damage through breakdown of the autonomous nervous system and subsequent massive cytokine release. This review highlights the actual knowledge on these proinflammatory effects of brain death on IRI in liver transplantation.
  
  
  RESULTS
  Brain death affects IRI either through hemodynamical or molecular effects with proinflammatory activation. Immunological effects are mainly mediated through Kupffer cell activation, leading to TNF-α and TLR4 amplification. Proinflammatory cytokines such as interleukin (IL)-6, IL-10, TNF-β and MIP-1α are released, together with activation of the innate immune system via natural killer cells and natural killer T cells, which promote organ damage and activation of fibrosis. Preprocurement treatment regimens attempt to hamper inflammatory response by the application of methylprednisolone or thymoglobulin to the donor. Selective P-selectin antagonism resulted in improved function in marginal liver grafts. Inhaled nitric oxide was found to reduce apoptosis in liver grafts. Other medications like the immunosuppressant tacrolimus produced conflicting results regarding organ protection. Furthermore, improved organ storage after procurement - such as machine perfusion - can diminish effects of IRI in a clinical setting.
  
  
  CONCLUSIONS
  Brain death plays a fundamental role in the regulation of molecular markers triggering inflammation and IRI-related tissue damage in liver transplants. Although several treatment options have reached clinical application, to date, the effects of brain death during donor conditioning and organ procurement remain relevant for organ function and survival.
authors.affiliation: Department of Visceral, Transplant and Thoracic Surgery, Center for Operative Medicine, Medical University Innsbruck, Innsbruck, Austria.
authors.forename: Tomasz
authors.initials: T
authors.lastname: Dziodzio
authors.forename: Matthias
authors.initials: M
authors.lastname: Biebl
authors.forename: Johann
authors.initials: J
authors.lastname: Pratschke
mesh_terms: D015415:Biomarkers / Q000378:metabolism; D001926:Brain Death / Q000378:metabolism / Q000503:physiopathology*; D006801:Humans; D008099:Liver / Q000378:metabolism / Q000503:physiopathology*; D016031:Liver Transplantation; D015427:Reperfusion Injury / Q000378:metabolism / Q000503:physiopathology*; D014019:Tissue Donors; D009927:Tissue and Organ Procurement
chemical_list: D015415:Biomarkers