title: HTK-N, a modified HTK solution, decreases preservation injury in a model of microsteatotic rat liver transplantation.
abstract: BACKGROUND
  Ischemia/reperfusion injury is an obstacle especially in steatotic livers, including those with steatosis induced by acute toxic stress. Recently, a modified histidine-tryptophan-ketoglutarate (HTK) solution, HTK-N, has been developed. This solution contains N-acetylhistidine, amino acids, and iron chelators. This study was designed to test the effects of HTK-N on preservation injury to rat livers after acute toxic injury.
  
  
  METHODS
  Microvesicular steatosis was induced by a single dose of ethanol (8 g/kg BW). Livers were harvested and stored at 4 °C for 8 h with HTK or HTK-N before transplantation. Tissue and blood samples were taken at 1, 8, and 24 h after reperfusion to compare serum liver enzymes (aspartate aminotransferase, alanine aminotransferase, and lactate dehydrogenase), standard histology, and immunohistochemistry for myeloperoxidase (MPO), caspase-3, and inducible nitric oxide synthase. Survival was compared after 1 week. For statistics, Analysis of Variance and t test were used.
  
  
  RESULTS
  HTK-N improved survival from 12.5% in HTK to 87.5% (p < 0.05). Furthermore, liver enzymes were decreased to 2-75% of HTK values (p < 0.05). Necrosis and leukocyte infiltration and MPO, caspase-3, and iNOS expression after transplantation were decreased (p < 0.05).
  
  
  CONCLUSIONS
  This study demonstrates that HTK-N protects liver grafts with microvesicular steatosis caused by acute toxic injury from cold ischemic injury better than standard HTK most likely via inhibition of hypoxic injury and oxidative stress and amelioration of the inflammatory reaction occurring upon reperfusion.
authors.affiliation: Department of General and Transplant Surgery, Ruprecht-Karls-University, Im Neuenheimer Feld 110, 69120, Heidelberg, Germany.
authors.forename: Qinlong
authors.initials: Q
authors.lastname: Liu
authors.forename: Helge
authors.initials: H
authors.lastname: Bruns
authors.forename: Daniel
authors.initials: D
authors.lastname: Schultze
authors.forename: Yi
authors.initials: Y
authors.lastname: Xue
authors.forename: Markus
authors.initials: M
authors.lastname: Zorn
authors.forename: Christa
authors.initials: C
authors.lastname: Flechtenmacher
authors.forename: Beate K
authors.initials: BK
authors.lastname: Straub
authors.forename: Ursula
authors.initials: U
authors.lastname: Rauen
authors.forename: Peter
authors.initials: P
authors.lastname: Schemmer
mesh_terms: D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D001219:Aspartate Aminotransferases / Q000097:blood; D003080:Cold Temperature; D000431:Ethanol / Q000633:toxicity; D005234:Fatty Liver / Q000473:pathology* / Q000601:surgery; D005260:Female; D005947:Glucose / Q000737:chemistry; D006639:Histidine / Q000031:analogs & derivatives* / Q000032:analysis; D007502:Iron Chelating Agents; D007770:L-Lactate Dehydrogenase / Q000097:blood; D008099:Liver / Q000098:blood supply / Q000473:pathology; D016031:Liver Transplantation / Q000401:mortality / Q000473:pathology; D008353:Mannitol / Q000737:chemistry; D055806:Microvessels / Q000187:drug effects / Q000473:pathology; D019188:Organ Preservation Solutions; D011189:Potassium Chloride / Q000737:chemistry; D011343:Procaine / Q000737:chemistry; D051381:Rats; D017207:Rats, Sprague-Dawley; D015996:Survival Rate
chemical_list: C039984:Bretschneider cardioplegic solution; D007502:Iron Chelating Agents; D019188:Organ Preservation Solutions; D000431:Ethanol; D008353:Mannitol; D006639:Histidine; D011343:Procaine; D011189:Potassium Chloride; D007770:L-Lactate Dehydrogenase; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D005947:Glucose; C023495:N-acetylhistidine