title: Graft reconditioning with nitric oxide gas in rat liver transplantation from cardiac death donors.
abstract: BACKGROUND
  Liver transplant outcomes using grafts donated after cardiac death (DCD) remain poor.
  
  
  METHODS
  We investigated the effects of ex vivo reconditioning of DCD grafts with venous systemic oxygen persufflation using nitric oxide gas (VSOP-NO) in rat liver transplants. Orthotopic liver transplants were performed in Lewis rats, using DCD grafts prepared using static cold storage alone (group-control) or reconditioning using VSOP-NO during cold storage (group-VSOP-NO). Experiment I: In a 30-min warm ischemia model, graft damage and hepatic expression of inflammatory cytokines, endothelial nitric oxide synthase (eNOS), inducible nitric oxide synthase (iNOS), and endothelin-1 (ET-1) were examined, and histologic analysis was performed 2, 6, 24, and 72 hr after transplantation. Experiment II: In a 60-min warm ischemia model, grafts were evaluated 2 hr after transplantation (6 rats/group), and survival was assessed (7 rats/group).
  
  
  RESULTS
  Experiment I: Group-VSOP-NO had lower alanine aminotransferase (ALT) (P<0.001), hyaluronic acid (P<0.05), and malondialdehyde (MDA) (P<0.001), hepatic interleukin-6 expression (IL-6) (P<0.05), and hepatic tumor necrosis factor-alpha (TNF-α) expression (P<0.001). Hepatic eNOS expression (P<0.001) was upregulated, whereas hepatic iNOS (P<0.01) and ET-1 (P<0.001) expressions were downregulated. The damage of hepatocyte and sinusoidal endothelial cells (SECs) were lower in group-VSOP-NO.Experiment II: VSOP-NO decreased ET-1 and 8-hydroxy-2'deoxyguanosine (8-OHdG) expression and improved survival after transplantation by 71.4% (P<0.01).
  
  
  CONCLUSIONS
  These results suggest that VSOP-NO effectively reconditions warm ischemia-damaged grafts, presumably by decreasing ET-1 upregulation and oxidative damage.
authors: 1 Department of Hepatobiliary, Pancreas and Transplant Surgery, Kyoto University, Kyoto, Japan. 2 Institute for Laboratory Animal Science and Experimental Surgery, RWTH-Aachen University, Aachen, Germany. 3 Address correspondence to: Shintaro Yagi, M.D., Ph.D., Department of Hepatobiliary, Pancreas and Transplant Surgery, Kyoto University, 54 Kawaharacho, Shogoin, Sakyo-ku, Kyoto, 606-8507, Japan.
authors: Shoichi
authors: S
authors: Kageyama
authors: Shintaro
authors: S
authors: Yagi
authors: Hirokazu
authors: H
authors: Tanaka
authors: Shunichi
authors: S
authors: Saito
authors: Kazuyuki
authors: K
authors: Nagai
authors: Koichiro
authors: K
authors: Hata
authors: Yasuhiro
authors: Y
authors: Fujimoto
authors: Yasuhiro
authors: Y
authors: Ogura
authors: Rene
authors: R
authors: Tolba
authors: Uemoto
authors: U
authors: Shinji
mesh_terms: D000080242:8-Hydroxy-2'-Deoxyguanosine; D000410:Alanine Transaminase / Q000378:metabolism; D000818:Animals; D050377:Cold Ischemia; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D019610:Cytoprotection; D003849:Deoxyguanosine / Q000031:analogs & derivatives / Q000378:metabolism; D019332:Endothelin-1 / Q000235:genetics / Q000378:metabolism; D005740:Gases; D006820:Hyaluronic Acid / Q000378:metabolism; D018836:Inflammation Mediators / Q000378:metabolism; D008099:Liver / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology / Q000601:surgery*; D016031:Liver Transplantation / Q000009:adverse effects*; D008315:Malondialdehyde / Q000378:metabolism; D023421:Models, Animal; D009569:Nitric Oxide / Q000494:pharmacology*; D052247:Nitric Oxide Synthase Type II / Q000235:genetics / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D011917:Rats, Inbred Lew; D015427:Reperfusion Injury / Q000209:etiology / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D013997:Time Factors; D052096:Warm Ischemia / Q000009:adverse effects
chemical_list: D016207:Cytokines; D019332:Endothelin-1; D005740:Gases; D018836:Inflammation Mediators; D012333:RNA, Messenger; D009569:Nitric Oxide; D008315:Malondialdehyde; D000080242:8-Hydroxy-2'-Deoxyguanosine; D006820:Hyaluronic Acid; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III; C496318:Nos2 protein, rat; C496316:Nos3 protein, rat; D000410:Alanine Transaminase; D003849:Deoxyguanosine