Abstract
Background: Brain death impairs donor organ quality and accelerates immune responses after transplantation. Detailed aspects of immune activation following brain death remain unclear. We have established a mouse model and investigated the immediate consequences of brain death and anesthesia on immune responses. Methods: C57JBI/6 mice (n = 6/group) were anesthetized with isoflurane (ISF) or ...
Abstract
Background: Brain death impairs donor organ quality and accelerates immune responses after transplantation. Detailed aspects of immune activation following brain death remain unclear. We have established a mouse model and investigated the immediate consequences of brain death and anesthesia on immune responses. Methods: C57JBI/6 mice (n = 6/group) were anesthetized with isoflurane (ISF) or ketamine/xylazine (KX); subsequently, animals underwent brain death induction and were followed for 3 h under continuous ventilation. Blood pressure was monitored continuously and animals were resuscitated with normal saline to achieve normotension. Immune activation in brain dead animals was analyzed by IFN-gamma-ELispot, MLR, and flow-cytometry. Sham-operated and naive animals served as controls. Results: Blood pressure remained stable in both BD/KX and BD/ISF animals during the 3 h observation time. Brain death was linked to systemic immune activation: IFN gamma-expression of splenocytes and lymphocyte proliferation rates was significantly elevated subsequent to brain death (p<0.02, <0.01); T-cell activation markers CD28 and CD69 had increased in brain dead animals (p<0.03, <0.02). Isoflurane treatment in sham controls throughout the observation period (3.5 h) revealed anesthesia associated IFN gamma-expression and lymphocyte activation which were not observed when animals were treated with ketamine/xylazine (p<0.04, <0.009). Conclusions: This study reports on a reproducible and hemodynamically stable brain death mouse model. Hemodynamic stability was not impacted through either isoflurane or ketamine/xylazine induction. Of clinical relevance, prolonged anesthesia with isoflurane had been linked to pro-inflammatory cytokine activation. Brain death caused systemic immune activation in organ donors. (C) 2012 Elsevier B.V. All rights reserved.
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