title: Hydrogen-enriched preservation protects the isogeneic intestinal graft and amends recipient gastric function during transplantation.
abstract: BACKGROUND
  Inhaled hydrogen gas exerts antioxidant and anti-inflammatory effects in rat intestinal transplantation. Here, we investigated whether ex vivo donor organ treatment with dissolved hydrogen would prevent intestinal graft injury.
  
  
  METHODS
  Isogeneic intestinal transplantation was performed in Lewis rats with vascular flush, luminal preservation, and cold graft storage in nitrogen-bubbled (SITxN2) or hydrogen-bubbled (SITxH2) preservation solution. Lactated Ringer's solution and 3-hr cold ischemia time were used for mechanistic investigations, whereas survival experiments were performed with University of Wisconsin solution and 6-hr cold ischemia time.
  
  
  RESULTS
  During the early phase of ischemia-reperfusion injury, hydrogen-enriched solution significantly preserved mucosal graft morphology, diminished graft malondialdehyde levels demonstrating substantial reduction potential and blunted proinflammatory molecular responses (early growth response gene [EGR-1], interleukin [IL]-6, IL-1ß, and inducible nitric oxide synthase) within the reperfused intestinal graft muscularis. During the late phase of ischemia-reperfusion injury, circulating IL-6 protein and lactate dehydrogenase levels were significantly ameliorated in SITxH2 animals, which were associated with a favorable functional outcome in in vivo liquid gastrointestinal transit and recipient solid gastric emptying of chrome steel balls, and marked prevention of the posttransplant associated suppression of in vitro muscarinic jejunal contractility. Reflecting improved graft preservation, hydrogen preloading of grafts increased recipient survival rates from 41% to 80%. Anti-inflammatory and antiapoptotic heme oxygenase-1 was significantly upregulated in the hydrogen-treated graft muscularis but not mucosa before reperfusion.
  
  
  CONCLUSIONS
  Graft preloading with hydrogen demonstrated superior morphologic and functional graft protection in rodent intestinal transplantation, ultimately facilitating recipient survival. Antioxidant capacity and muscularis heme oxygenase-1 upregulation are possible protective mechanisms.
authors.affiliation: Department of Medicine, University of Pittsburgh, Pittsburgh, PA, USA.
authors.forename: Bettina M
authors.initials: BM
authors.lastname: Buchholz
authors.forename: Kosuke
authors.initials: K
authors.lastname: Masutani
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Kawamura
authors.forename: Ximei
authors.initials: X
authors.lastname: Peng
authors.forename: Yoshiya
authors.initials: Y
authors.lastname: Toyoda
authors.forename: Timothy R
authors.initials: TR
authors.lastname: Billiar
authors.forename: Anthony J
authors.initials: AJ
authors.lastname: Bauer
authors.forename: Atsunori
authors.initials: A
authors.lastname: Nakao
mesh_terms: D000241:Adenosine / Q000494:pharmacology; D000493:Allopurinol / Q000494:pharmacology; D000818:Animals; D050377:Cold Ischemia; D005772:Gastrointestinal Transit / Q000187:drug effects / Q000502:physiology; D005978:Glutathione / Q000494:pharmacology; D006085:Graft Survival / Q000187:drug effects / Q000502:physiology; D051547:Heme Oxygenase-1 / Q000378:metabolism; D006859:Hydrogen / Q000494:pharmacology*; D007328:Insulin / Q000494:pharmacology; D007552:Isotonic Solutions / Q000494:pharmacology; D007583:Jejunum / Q000187:drug effects* / Q000378:metabolism / Q000637:transplantation*; D008297:Male; D023421:Models, Animal; D009584:Nitrogen / Q000494:pharmacology; D019188:Organ Preservation Solutions / Q000494:pharmacology*; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology; D011887:Raffinose / Q000494:pharmacology; D051381:Rats; D011917:Rats, Inbred Lew; D000077331:Ringer's Solution; D013270:Stomach / Q000187:drug effects* / Q000502:physiology*; D014185:Transplantation, Isogeneic
chemical_list: D007328:Insulin; D007552:Isotonic Solutions; D019188:Organ Preservation Solutions; C055206:University of Wisconsin-lactobionate solution; D000493:Allopurinol; D006859:Hydrogen; D000077331:Ringer's Solution; D051547:Heme Oxygenase-1; D005978:Glutathione; D000241:Adenosine; D011887:Raffinose; D009584:Nitrogen