title: Luminal solutions protect mucosal barrier during extended preservation.
abstract: BACKGROUND
  Mucosal barrier injury during intestinal preservation (IP) and transplantation favors life-threatening infections. Luminal delivery of solutions containing amino acids or polyethylene glycols (PEGs) may improve preservation results and reduce this injury. We tested if solutions containing glutamine and PEG influence the mucosal injury.
  
  
  METHODS
  Rat intestines were perfused and stored in Viaspan-University of Wisconsin solution. Before IP, a PEG 3350 solution was introduced intraluminally alone (group 1) or supplemented with 40 mmol/L L-glutamine (group 2). Controls underwent vascular flush alone (group 3). Preservation injury was evaluated after 8, 14, and 24 h by histology and goblet cell count. Tight-junction proteins zonula occludens-1, claudin-3, claudin-4, and caveolin-1 were studied by immunofluorescence. Maltase and caspase-3 activity were also analyzed.
  
  
  RESULTS
  Group 1 showed mild edema at 8 h and mucosal disruption by 24 h; these features were greatly improved in group 2 where continuous mucosa was found after 24 h of IP. Intestines in group 3 did worse at all time points with subepithelial edema (Park/Chiu grade 3) and marked goblet cell depletion; caspase-3 activity was lowest in group 2. Tight-junction proteins varied continuously during IP; zonula occludens-1 expression and colocalization with claudins decreased significantly in group 3 but not in other groups. Claudin-3 was distinctly localized in the membrane, but stained diffuse, cytoplasmic at later time-points. Claudin-4 changed to a cytoplasmic granular pattern. No caveolin-1 colocalization was observed.
  
  
  CONCLUSIONS
  Luminal PEG and glutamine delay epithelial breakdown and preserve several important mucosal features during extended IP.
authors.affiliation: Department of Surgery/Laboratory for Transplantation and Regenerative Medicine, Institute of Clinical Sciences, Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden. Electronic address: mihai.oltean@surgery.gu.se.
authors.forename: Mihai
authors.initials: M
authors.lastname: Oltean
authors.affiliation: Department of Surgery/Laboratory for Transplantation and Regenerative Medicine, Institute of Clinical Sciences, Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden.
authors.forename: Mats
authors.initials: M
authors.lastname: Hellström
authors.affiliation: Department of Surgery/Laboratory for Transplantation and Regenerative Medicine, Institute of Clinical Sciences, Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden; First Surgical Clinic, University of Medicine and Pharmacy, Cluj-Napoca, Romania.
authors.forename: Catalin
authors.initials: C
authors.lastname: Ciuce
authors.affiliation: Institute of Neuroscience and Physiology, Center for Brain Repair and Rehabilitation, University of Gothenburg, Gothenburg, Sweden.
authors.forename: Changlian
authors.initials: C
authors.lastname: Zhu
authors.affiliation: Department of Gastrosurgical research and Education, Institute of Clinical Sciences, Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden.
authors.forename: Anna
authors.initials: A
authors.lastname: Casselbrant
mesh_terms: D000818:Animals; D017209:Apoptosis; D053148:Caspase 3 / Q000378:metabolism; D005973:Glutamine / Q000494:pharmacology*; D020397:Goblet Cells / Q000473:pathology; D007413:Intestinal Mucosa / Q000378:metabolism / Q000473:pathology*; D007422:Intestines / Q000637:transplantation*; D008297:Male; D009926:Organ Preservation; D011092:Polyethylene Glycols / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012996:Solutions; D019108:Tight Junctions / Q000502:physiology
chemical_list: D012996:Solutions; D005973:Glutamine; D011092:Polyethylene Glycols; D053148:Caspase 3
keywords: Intestinal transplantation; Ischemia; Organ preservation; Preservation solutions; Tight junctions