title: Impact of venous-systemic oxygen persufflation with nitric oxide gas on steatotic grafts after partial orthotopic liver transplantation in rats.
abstract: BACKGROUND
  Steatotic livers are associated with poor graft function after transplantation. We investigated the effects of venous-systemic oxygen persufflation with nitric oxide gas (VSOP-NO) on steatotic partial livers after transplantation.
  
  
  METHODS
  Steatotic livers induced by fasting for 2 days and subsequent refeeding for 3 days with a fat-free, carbohydrate-rich diet were reduced in size by 50% and transplanted into Lewis rats after 3 hr of cold storage in histidine-tryptophan-ketoglutarate solution. Gaseous oxygen with nitric oxide (40 ppm) was insufflated into the grafts through the suprahepatic vena cava during cold storage (VSOP-NO group; n=20). Transplantation of cold-static stored steatotic and normal grafts served as controls (Steatotic-Control and Normal-Control, respectively; n=20 for each group).
  
  
  RESULTS
  The graft microcirculation and portal venous flow were increased by VSOP-NO compared with Steatotic-Control (P<0.001 for both). Serum alanine aminotransferase and interleukin-6 levels were lower in VSOP-NO versus Steatotic-Control group (P=0.03 for both). Messenger RNA expression for inducible nitric oxide synthase, which was increased in Steatotic-Control livers 3 hr after transplantation (P=0.02 vs. that at 1 hr), was suppressed by VSOP-NO. Although serum nitrite levels were decreased 1 hr after transplantation in Steatotic-Control (P=0.06 vs. Normal-Control), the VSOP-NO group showed increased levels comparable to Normal-Control. In livers 24 hr after transplantation, moderate vacuolization of hepatocytes by histology with the immunohistochemical expression of nitrotyrosine, indicative of nitrative stress, was found in Steatotic-Control, whereas these findings were less apparent in VSOP-NO-treated livers.
  
  
  CONCLUSIONS
  Application of VSOP-NO for steatotic partial livers reduces hepatocellular damage and improves graft viability and microcirculation after transplantation.
authors.affiliation: Institute for Laboratory Animal Science and Experimental Surgery, RWTH-Aachen University, Aachen, Germany.
authors.forename: Kazuyuki
authors.initials: K
authors.lastname: Nagai
authors.forename: Shintaro
authors.initials: S
authors.lastname: Yagi
authors.forename: Mamdouh
authors.initials: M
authors.lastname: Afify
authors.forename: Christian
authors.initials: C
authors.lastname: Bleilevens
authors.forename: Shinji
authors.initials: S
authors.lastname: Uemoto
authors.forename: Rene H
authors.initials: RH
authors.lastname: Tolba
mesh_terms: D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D005234:Fatty Liver / Q000503:physiopathology*; D015850:Interleukin-6 / Q000097:blood; D008099:Liver / Q000473:pathology; D008102:Liver Circulation; D016031:Liver Transplantation / Q000379:methods*; D008297:Male; D009569:Nitric Oxide / Q000008:administration & dosage*; D010100:Oxygen / Q000378:metabolism*; D051381:Rats; D011917:Rats, Inbred Lew
chemical_list: D015850:Interleukin-6; D009569:Nitric Oxide; D000410:Alanine Transaminase; D010100:Oxygen