Activation of the Innate Immune System in Brain-Dead Donors Can Be Reduced by Luminal Intestinal Preservation During Organ Procurement Surgery - A Porcine Model

Transpl Int. 2024 Oct 31:37:13569. doi: 10.3389/ti.2024.13569. eCollection 2024.

Abstract

Organs obtained from brain dead donors can have suboptimal outcomes. Activation of the innate immune system and translocation of intestinal bacteria could be causative. Thirty two pigs were assigned to control, brain death (BD), BD + luminal intestinal polyethylene glycol (PEG), and BD + luminal intestinal University of Wisconsin solution (UW) groups. Animals were observed for 360 min after BD before organ retrieval. 2,000 mL luminal intestinal preservation solution was instilled into the duodenum at the start of organ procurement. Repeated measurements of plasma C3a, Terminal Complement Complex (TCC), IL-8, TNF, and lipopolysaccharide binding protein were analysed by immunoassays. C3a was significantly higher in the BD groups compared to controls at 480 min after brain death. TCC was significantly higher in BD and BD + UW, but not BD + PEG, compared to controls at 480 min. TNF was significantly higher in the BD group compared to all other groups at 480 min. LPS binding protein increased following BD in all groups except BD + PEG, which at 480 min was significantly lower compared with all other groups. Brain death induced innate immune system activation was decreased by luminal preservation using PEG during organ procurement, possibly due to reduced bacterial translocation.

Keywords: C3a; brain dead donor; innate immune system; lipopolysaccharide binding protein; luminal intestinal preservation; organ procurement and porcine model; terminal complement complex.

MeSH terms

  • Acute-Phase Proteins / metabolism
  • Adenosine
  • Allopurinol
  • Animals
  • Brain Death* / immunology
  • Carrier Proteins
  • Glutathione
  • Immunity, Innate*
  • Insulin
  • Interleukin-8 / metabolism
  • Intestines* / immunology
  • Membrane Glycoproteins
  • Models, Animal
  • Organ Preservation Solutions*
  • Organ Preservation* / methods
  • Polyethylene Glycols
  • Raffinose
  • Swine
  • Tissue Donors
  • Tissue and Organ Procurement / methods
  • Tumor Necrosis Factor-alpha / metabolism

Substances

  • Organ Preservation Solutions
  • lipopolysaccharide-binding protein
  • Allopurinol
  • University of Wisconsin-lactobionate solution
  • Raffinose
  • Polyethylene Glycols
  • Adenosine
  • Insulin
  • Acute-Phase Proteins
  • Tumor Necrosis Factor-alpha
  • Interleukin-8
  • Carrier Proteins
  • Glutathione
  • Membrane Glycoproteins

Grants and funding

The author(s) declare that financial support was received for the research, authorship, and/or publication of this article. This work was funded by: the Novo Nordic Foundation (NNF19OC0056466), Aase and Ejnar Danielsens Foundation (19-10-0392), A.P. Moeller Maersk Foundation for Medical Research (19-L-0132), and the Danish Renal Disease Research Foundation.