Prevention of a leaky gut by luminal preservation following Brain Death, may reduce Innate Immune Activation.

Background: Organs obtained from brain dead (BD) donors often have worse outcomes. Activation of the complement system and translocation of intestinal bacteria could be causative. We aimed to examine activation of the complement system following BD and evaluate the systemic and local effect of adding luminal intestinal preservation to classical vascular preservation. Methods and material: BD was induced in 30 pigs (four groups: control (n=7), BD alone (n=8), BD + luminal intestinal polyethylene glycol (PEG, n=7) and BD + luminal intestinal University of Wisconsin solution (UW, n=8) using a previously validated method and all animals were observed for 6 hours before organ retrieval. In the PEG and UW groups, 2000 ml of the selected solution was instilled into the duodenum during the organ procurement surgery. Repeated measurements of C3a, Terminal Complement Complex (TCC), IL-8 and TNF were performed in plasma at baseline, BD, 30, 60, 120, 240 and 360 minutes after BD, and following the intestinal intervention (480). Plasma lipopolysaccharide binding protein (LPS-BP) was measured at baseline, BD, and 480 minutes after BD. All were normalised to albumin concentration. Biopsies were taken from jejunum and ileum at time of removal and following 8, 14 and 24 hours of static cold storage (SCS) using UW. Preliminary analysis has been performed at 24 hours of SCS for the BD groups, full histology will be available soon. Results: All animals were kept circulatory- and respiratory stable until organ procurement. At 480 minutes, C3a was significantly higher in BD, BD+PEG, and BD+UW groups compared to control group (all p<0.05) (fig. 1A). TCC was significantly higher in the combined BD group compared to control at 360 minutes, at 480 minutes, the BD and BD+UW groups were significantly higher compared to the control group (all p<0.05) (fig. 1B). IL-8 and TNF were significantly higher in the BD group compared to all other groups at 480 minutes (p=0,003 and p=0.001) (fig. 1C and D). LPS-BP increased following induction of BD in all groups except BD+PEG, which at 480 minutes were significantly lower (p=0.002) (fig. 1E and F) compared with all other groups. Preliminary biopsies from the Jejunum after 24 hours of SCS show a reduced median Chiu/Park score in the BD+PEG (2.5) and BD+UW (2.0) groups compared to the BD group (fig. 2). Conclusion: The complement system is activated following BD independently of intestinal and luminal preservation and may lead to inflammation. Luminal intestinal preservation during organ procurement led to lower Chiu/Park scores, and reduced cytokine and LPS-BP expression, which may be due to reduced bacterial translocation occurring during surgery independent of BD. Luminal PEG intervention may be combined with early innate immune system inhibition in BD donors to prevent systemic inflammation, which hampers organ function.