title: Hemoadsorption to improve organ recovery from brain-dead organ donors: a novel therapy for a novel indication?
abstract: While brain-dead organ donors represent the majority of the organ donor pool, it appears that graft survival is adversely affected by brain death itself. Brain death has been shown to cause severe disturbances in the hormonal, hemodynamic and immunological homeostasis, which could in part be responsible for the inferior outcome of organs originating from brain-dead donors compared to living donors. Hemodynamic effects of brain death lead to a wide fluctuation in mean perfusion pressures, blood flow to the organs and systemic oxygen consumption, altering regional perfusion. In addition, a wide array of immunological changes has been shown to occur after brain death contributing to organ injury and hemodynamic instability. Recent studies have shown that brain death upregulates multiple lymphocyte- and macrophage-derived cytokines and the injured brain itself may be the source of proinflammatory factors such as S100B. This increased inflammatory response seen during and immediately after brain death has also been associated with poor allograft function. Furthermore, there is evidence to suggest that the massive inflammatory response seen in brain-dead donors could also lead to increased immunogenicity and accelerated allograft rejection after transplantation. Hence, we hypothesize that nonspecific downregulation of this inflammatory response by hemoadsorption could potentially lead to improved donor organ and allograft function. As a 'proof of concept' we tested the ability of a novel hemoadsorbent to remove S100B in vitro using two human glioblastoma cell lines. Our results indicate a >80% reduction in S100B after 2 h of circulation with the sorbent.
authors.affiliation: CRISMA Laboratory (Clinical Research, Investigation, and Systems Modeling of Acute Illness), Department of Critical Care Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261, USA.
authors.forename: Ramesh
authors.initials: R
authors.lastname: Venkataraman
authors.forename: Mingchen
authors.initials: M
authors.lastname: Song
authors.forename: Rachel
authors.initials: R
authors.lastname: Lynas
authors.forename: John A
authors.initials: JA
authors.lastname: Kellum
mesh_terms: D001921:Brain / Q000378:metabolism; D001926:Brain Death / Q000097:blood* / Q000503:physiopathology; D001932:Brain Neoplasms / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor / Q000378:metabolism; D002478:Cells, Cultured / Q000737:chemistry; D016207:Cytokines / Q000097:blood / Q000378:metabolism; D005909:Glioblastoma / Q000378:metabolism / Q000473:pathology; D006084:Graft Rejection / Q000209:etiology / Q000517:prevention & control; D006085:Graft Survival; D006464:Hemoperfusion; D006801:Humans; D007249:Inflammation / Q000097:blood; D018836:Inflammation Mediators / Q000097:blood*; D007511:Ischemia / Q000517:prevention & control; D009414:Nerve Growth Factors; D010101:Oxygen Consumption; D064568:S100 Calcium Binding Protein beta Subunit; D009418:S100 Proteins / Q000097:blood* / Q000378:metabolism; D014019:Tissue Donors; D020858:Tissue and Organ Harvesting / Q000379:methods*; D014184:Transplantation, Homologous
chemical_list: D016207:Cytokines; D018836:Inflammation Mediators; D009414:Nerve Growth Factors; D064568:S100 Calcium Binding Protein beta Subunit; D009418:S100 Proteins; C579160:S100B protein, human