title: Direct peritoneal resuscitation improves survival and decreases inflammation after intestinal ischemia and reperfusion injury.
abstract: BACKGROUND
  Direct peritoneal resuscitation (DPR) has previously been shown to alter blood flow in the small bowel mesenteric vessels in models of intestinal ischemia. However, a survival advantage or its effects on local tissue inflammation have not been previously demonstrated. We hypothesized that DPR would increase survival and decrease intestinal tissue inflammation after intestinal ischemia and reperfusion (I/R) injury.
  
  
  METHODS
  Eight-week-old male C57Bl6J mice were anesthetized and underwent midline laparotomy. I/R and DPR groups were exposed to superior mesenteric artery occlusion for 60 min with a nontraumatic clamp. Immediately after removal of the clamp, 1 mL of phosphate-buffered saline, 1 mL of minimal essential media, or 1 mL of minimal essential media supplemented with fetal bovine serum, penicillin and/or streptomycin, and glutamine were placed into the abdominal cavity of DPR groups. Animals were then closed in two layers and allowed to reperfuse for 6 h (cytokine analysis, n = 6 per group) or 7 d (survival analysis, n = 10 per group). After 6 h of reperfusion, animals were euthanized. Intestines were harvested and homogenized. Extracts were quantified for total protein content (Bradford assay), myeloperoxidase activity, tissue inflammatory cytokine, and growth factor production. P < 0.05 was significant.
  
  
  RESULTS
  I/R caused marked intestinal ischemia, significant mortality, and a significant increase in tissue cytokine and growth factor levels (P < 0.05). Seven-day survival was 30% for I/R without treatment and rose to 60% with DPR therapy using phosphate-buffered saline as the dialysate. DPR using plain MEM or MEM with supplements after ischemia increased 7-d survival to 90% (P < 0.05). DPR also significantly decreased intestinal tissue levels of myeloperoxidase, as well as intestinal tissue levels of multiple growth factors and inflammatory cytokines.
  
  
  CONCLUSIONS
  DPR increases survival and decreases intestinal inflammation after intestinal I/R injury. Translational applications are readily achievable and should be considered for patients with intestinal ischemic pathology.
authors.affiliation: Section of Pediatric Surgery, Department of Surgery, Riley Hospital for Children at Indiana University Health and, The Indiana University School of Medicine, Indianapolis, Indiana.
authors.forename: Trevor D
authors.initials: TD
authors.lastname: Crafts
authors.affiliation: Section of Pediatric Surgery, Department of Surgery, Riley Hospital for Children at Indiana University Health and, The Indiana University School of Medicine, Indianapolis, Indiana.
authors.forename: Erin Bailey
authors.initials: EB
authors.lastname: Hunsberger
authors.affiliation: Section of Pediatric Surgery, Department of Surgery, Riley Hospital for Children at Indiana University Health and, The Indiana University School of Medicine, Indianapolis, Indiana.
authors.forename: Amanda R
authors.initials: AR
authors.lastname: Jensen
authors.affiliation: Section of Pediatric Surgery, Department of Surgery, Riley Hospital for Children at Indiana University Health and, The Indiana University School of Medicine, Indianapolis, Indiana.
authors.forename: Frederick J
authors.initials: FJ
authors.lastname: Rescorla
authors.affiliation: Section of Neonatology, Department of Pediatrics, Riley Hospital for Children at Indiana University Health and, The Indiana University School of Medicine, Indianapolis, Indiana.
authors.forename: Mervin C
authors.initials: MC
authors.lastname: Yoder
authors.affiliation: Section of Pediatric Surgery, Department of Surgery, Riley Hospital for Children at Indiana University Health and, The Indiana University School of Medicine, Indianapolis, Indiana. Electronic address: tmarkel@iupui.edu.
authors.forename: Troy A
authors.initials: TA
authors.lastname: Markel
mesh_terms: D000818:Animals; D016207:Cytokines / Q000378:metabolism; D004751:Enteritis / Q000209:etiology / Q000517:prevention & control; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism; D007413:Intestinal Mucosa / Q000378:metabolism; D007422:Intestines / Q000098:blood supply*; D008297:Male; D017538:Mesenteric Artery, Superior; D008810:Mice, Inbred C57BL; D009195:Peroxidase / Q000378:metabolism; D015427:Reperfusion Injury / Q000150:complications / Q000628:therapy*; D012151:Resuscitation / Q000379:methods*
chemical_list: D016207:Cytokines; D036341:Intercellular Signaling Peptides and Proteins; D009195:Peroxidase
keywords: Intestinal ischemia; Mesenteric ischemia; Necrotizing enterocolitis; Peritoneal resuscitation; Survival