Direct Peritoneal Resuscitation Reduces Intestinal Permeability after Brain Death

Background The profound inflammatory response associated with brain death is frequently cited as the reason organs procured from brain dead donors are associated with worse graft function. The intestine releases inflammatory mediators in other types of shock, but its role is brain death has not been well-studied. Direct peritoneal resuscitation (DPR) improves visceral organ blood flow and reduces inflammation after hemorrhagic shock. We hypothesized that use of DPR would maintain intestinal integrity and reduce circulating inflammatory mediators after brain death. Methods Brain death was induced in male Sprague-Dawley rats by inserting a 4F fogarty catheter into the epidural space and slowly inflating it. After herniation, rats were resuscitated with normal saline to maintain a mean arterial pressure of 80 mmHg and sacrificed and tissue collected immediately (time zero), or two, four, or six hours after brain death. Randomly-selected animals received DPR via an intraperitoneal injection of 30cc commercial peritoneal dialysis solution. Results Levels of pro-inflammatory cytokines including IL-1β and IL-6, as well as HMGB-1 and HSP70 were all increased after brain death and decreased with DPR. Fatty acid binding protein and lipopolysaccharide, both markers of intestinal injury, were increased in the serum after brain death and decreased with DPR. Immunohistochemistry staining for ZO-1 showed decreased intestinal tight junction integrity after brain death, which improved with DPR. Conclusions Intestinal permeability increases after brain death, and this contributes to the increased inflammation seen throughout the body. Using DPR prevents intestinal ischemia and helps preserve intestinal integrity. This suggests that using this novel therapy as an adjunct to the resuscitation of brain dead donors has the potential to reduce inflammation and potentially improve the quality of transplanted organs. Level of Evidence Level III therapeutic Disclosures: all authors have no conflicts of interest to disclose Presented as a podium presentation at the 76th Annual Meeting of the American Association for the Surgery of Trauma, September 13-16, 2017 Baltimore, MD. Corresponding Author: Jessica L Weaver, MD PhD, 550 S Jackson St, ACB 2nd floor, Rm A2J19, Louisville, KY 40292, jlweav08@louisville.edu © 2017 Lippincott Williams & Wilkins, Inc.

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