title: Perioperative glycine treatment attenuates ischemia/reperfusion injury and ameliorates smooth muscle dysfunction in intestinal transplantation.
abstract: BACKGROUND
  Ischemia/reperfusion evokes a functionally relevant inflammatory response within the muscularis propria of small bowel grafts by activation of resident macrophages and leukocyte recruitment. We hypothesized that immunomodulatory perioperative treatment with glycine attenuates the proinflammatory cascade and improves smooth muscle dysfunction of small bowel grafts.
  
  
  METHODS
  Orthotopic SBTx was performed in Lewis rats. Glycine (1 mg/g body weight) was infused (0.1 mL/g/hr) for 2 hr before harvest as preconditioning in the donor, and for 2 hr from the onset of reperfusion in the recipient. Transplanted vehicle (isotonic saline)-treated animals and naive animals served as controls. Rats were sacrificed after 3 hr and 24 hr. Leukocyte infiltration was investigated in muscularis whole mounts by immunohistochemistry. Mediator mRNA expression was determined by real-time-PCR. Jejunal circular smooth muscle contractility was assessed in a standard organ bath.
  
  
  RESULTS
  Compared with vehicle controls, glycine-treated graft muscularis expressed a significant alleviation in mRNA peak expression for IL-6, IL-1beta, ICAM-1, MCP-1, TNFalpha, COX-2, and iNOS. Also glycine-treated grafts exhibited significantly less infiltration with ED-1-positive macrophages and MPO-positive neutrophils as well as reduced apoptosis. Concurrent to these results, vehicle controls showed an 80% decrease in smooth muscle contractility, whereas glycine-treated animals exhibited only a 40% decrease in contractile activity compared with controls.
  
  
  CONCLUSIONS
  The data indicate that perioperative glycine treatment reduces the molecular and cellular inflammatory response within the grafts and improves smooth muscle dysfunction after transplantation. Therefore, the glycine-activated chloride channel on resident and infiltrating leukocytes could be a promising pharmacologic target to attenuate ischemia/reperfusion injury after ITx.
authors.affiliation: Department of Surgery, Rheinische Friedrich-Wilhelms-Universität Bonn, Bonn, Germany. nico.schaefer@ukb.uni-bonn.de
authors.forename: Nico
authors.initials: N
authors.lastname: Schaefer
authors.forename: Kazunori
authors.initials: K
authors.lastname: Tahara
authors.forename: Silke
authors.initials: S
authors.lastname: Schuchtrup
authors.forename: Martin V
authors.initials: MV
authors.lastname: Websky
authors.forename: Marcus
authors.initials: M
authors.lastname: Overhaus
authors.forename: Joachim
authors.initials: J
authors.lastname: Schmidt
authors.forename: Stefan
authors.initials: S
authors.lastname: Wirz
authors.forename: Kareem M
authors.initials: KM
authors.lastname: Abu-Elmagd
authors.forename: Jörg C
authors.initials: JC
authors.lastname: Kalff
authors.forename: Andreas
authors.initials: A
authors.lastname: Hirner
authors.forename: Andreas
authors.initials: A
authors.lastname: Türler
mesh_terms: D000818:Animals; D017209:Apoptosis; D051546:Cyclooxygenase 2 / Q000235:genetics; D017931:DNA Primers; D005786:Gene Expression Regulation; D005998:Glycine / Q000627:therapeutic use*; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics; D007378:Interleukins / Q000235:genetics; D007422:Intestines / Q000473:pathology / Q000637:transplantation*; D007432:Intraoperative Period; D008297:Male; D009130:Muscle, Smooth / Q000187:drug effects / Q000502:physiology* / Q000503:physiopathology; D052247:Nitric Oxide Synthase Type II / Q000235:genetics; D051381:Rats; D011917:Rats, Inbred Lew; D015427:Reperfusion Injury / Q000473:pathology / Q000517:prevention & control*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014185:Transplantation, Isogeneic / Q000473:pathology; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics
chemical_list: D017931:DNA Primers; D007378:Interleukins; D014409:Tumor Necrosis Factor-alpha; D018799:Intercellular Adhesion Molecule-1; D052247:Nitric Oxide Synthase Type II; D051546:Cyclooxygenase 2; D005998:Glycine