title: A novel method of preserving cardiac grafts using a hydrogen-rich water bath.
abstract: BACKGROUND
  Exogenously administered hydrogen exerts cytoprotective effects through anti-oxidant, anti-inflammatory, and anti-apoptotic mechanisms in various disease settings, including organ transplantation. Our objective in this study was to evaluate the efficacy of a novel cold storage device equipped with a hydrogen-rich water bath.
  
  
  METHODS
  The study used an established rat heterotopic transplantation model. Syngeneic heart grafts from elderly donors (60- to 70-week-old Lewis rats) or allografts from adult donors (12-week-old Brown Norway rats) were exposed to prolonged cold preservation. The cardiac grafts were stored in plastic bags containing Celsior, which were immersed in the cold water bath equipped with an electrolyzer to saturate the water with hydrogen. The cardiac grafts then were heterotopically engrafted into Lewis rat recipients.
  
  
  RESULTS
  In both experimental settings, serum troponin I and creatine phosphokinase were markedly elevated 3 hours after reperfusion in the control grafts without hydrogen treatment. The grafts exhibited prominent inflammatory responses, including neutrophil infiltration and the upregulation of messenger RNAs for pro-inflammatory cytokines and chemokines. Myocardial injury and inflammatory events were significantly attenuated by organ storage in the hydrogen-rich water bath. The grafts stored using the hydrogen-rich water bath also exhibited less mitochondrial damage and a higher adenosine triphosphate content.
  
  
  CONCLUSIONS
  Hydrogen delivery to cardiac grafts during cold preservation using a novel hydrogen-supplemented water bath efficiently ameliorated myocardial injury due to cold ischemia and reperfusion. This new device to saturate organs with hydrogen during cold storage merits further investigation for possible therapeutic and preventative use during transplantation.
authors.affiliation: Department of Cardiothoracic Surgery, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA.
authors.forename: Kentaro
authors.initials: K
authors.lastname: Noda
authors.forename: Norihisa
authors.initials: N
authors.lastname: Shigemura
authors.forename: Yugo
authors.initials: Y
authors.lastname: Tanaka
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Kawamura
authors.forename: Sang
authors.initials: S
authors.lastname: Hyun Lim
authors.forename: Kenichi
authors.initials: K
authors.lastname: Kokubo
authors.forename: Timothy R
authors.initials: TR
authors.lastname: Billiar
authors.forename: Christian A
authors.initials: CA
authors.lastname: Bermudez
authors.forename: Hirosuke
authors.initials: H
authors.lastname: Kobayashi
authors.forename: Atsunori
authors.initials: A
authors.lastname: Nakao
mesh_terms: D000818:Animals; D050377:Cold Ischemia; D004187:Disaccharides / Q000494:pharmacology; D004573:Electrolytes / Q000494:pharmacology; D005260:Female; D005971:Glutamates / Q000494:pharmacology; D005978:Glutathione / Q000494:pharmacology; D016027:Heart Transplantation; D051547:Heme Oxygenase-1; D006639:Histidine / Q000494:pharmacology; D006859:Hydrogen / Q000494:pharmacology; D008297:Male; D008353:Mannitol / Q000494:pharmacology; D009206:Myocardium / Q000648:ultrastructure; D009926:Organ Preservation / Q000379:methods*; D019188:Organ Preservation Solutions / Q000494:pharmacology; D051381:Rats; D011914:Rats, Inbred BN; D011917:Rats, Inbred Lew; D060888:Real-Time Polymerase Chain Reaction; D014022:Tissue Survival; D014184:Transplantation, Homologous; D014867:Water
chemical_list: C088453:Celsior; D004187:Disaccharides; D004573:Electrolytes; D005971:Glutamates; D019188:Organ Preservation Solutions; D014867:Water; D008353:Mannitol; D006639:Histidine; D006859:Hydrogen; D051547:Heme Oxygenase-1; D005978:Glutathione