title: Induction of intestinal ischemia reperfusion injury by portal vein outflow occlusion in rats.
abstract: BACKGROUND
  Intestinal ischemia can occur from mesenteric artery (MA) occlusion and portal vein (PV) occlusion. The degree and mechanisms of ischemia/reperfusion (I/R) injury in these conditions may differ. Metabolic changes are seen early in I/R. This study compares tissue histology, inflammation, and metabolic response during small bowel I/R due to superior MA or PV occlusion.
  
  
  METHODS
  Anesthetized male Wistar rats (250-300 g) underwent laparotomy followed by MA or PV occlusion for 40 min. After 120 min of reperfusion, small bowel tissue was collected. The expression of heat shock protein (HSP)-32 and HSP70 was evaluated to compare physiological stress responses between groups. Metabolic profiles were obtained using (1)H-nuclear magnetic resonance spectroscopy (NMR)-based quantitative metabolomics. Histological injury of small bowel was graded from 0 (normal) to 4 (extensive ischemic damage).
  
  
  RESULTS
  Protein expression of HSP32 and HSP70 increased when compared to sham but was not different in the MA I/R and PV I/R groups. Metabolic profiles demonstrated decreased glucose levels and highly elevated tissue lactate and amino acids and fatty acids following I/R, with more pronounced changes with PV occlusion. Lipid peroxidation was equally increased in both groups, while depletion of reduced glutathione (GSH) was more severe with MA occlusion. The epithelial necrosis score was higher with MA (3.5 ± 0.6) than with PV occlusion (2.3 ± 0.8).
  
  
  CONCLUSIONS
  Histological injury of the intestine is less pronounced following PV occlusion, most likely due to higher oxygen and substrate availability during I/R by PV occlusion. This conclusion is supported by a more pronounced metabolic synthetic response (increased glycolysis and fatty acid and amino acid accumulation) with PV occlusion, while oxidative stress was higher with MA occlusion. The inflammatory response showed little difference between the groups.
authors.affiliation: Department of Surgery, Division of Transplantation, University of California, San Francisco, CA 94143-0648, USA.
authors.forename: Marco
authors.initials: M
authors.lastname: Vincenti
authors.forename: Matthias
authors.initials: M
authors.lastname: Behrends
authors.forename: Kim
authors.initials: K
authors.lastname: Dang
authors.forename: Yeon H
authors.initials: YH
authors.lastname: Park
authors.forename: Ryutaro
authors.initials: R
authors.lastname: Hirose
authors.forename: Annabel
authors.initials: A
authors.lastname: Blasi-Ibanez
authors.forename: Tao
authors.initials: T
authors.lastname: Liu
authors.forename: Natalie J
authors.initials: NJ
authors.lastname: Serkova
authors.forename: Claus U
authors.initials: CU
authors.lastname: Niemann
mesh_terms: D000818:Animals; D003251:Constriction, Pathologic / Q000503:physiopathology; D004195:Disease Models, Animal; D006019:Glycolysis; D018840:HSP70 Heat-Shock Proteins / Q000378:metabolism; D006419:Heme Oxygenase (Decyclizing) / Q000378:metabolism; D007413:Intestinal Mucosa / Q000473:pathology; D007421:Intestine, Small / Q000098:blood supply / Q000503:physiopathology*; D008297:Male; D008638:Mesenteric Arteries; D009336:Necrosis / Q000473:pathology; D018384:Oxidative Stress; D010100:Oxygen / Q000378:metabolism; D011169:Portal Vein; D051381:Rats; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000503:physiopathology*
chemical_list: D018840:HSP70 Heat-Shock Proteins; D006419:Heme Oxygenase (Decyclizing); C491523:Hmox1 protein, rat; D010100:Oxygen