title: Warm HTK donor pretreatment reduces liver injury during static cold storage in experimental rat liver transplantation.
abstract: BACKGROUND
  Organ shortage has led to an increased number of transplantations from extended criteria donors. These organs are more vulnerable to ischemia-reperfusion injury. Thus, improvement of organ preservation is needed. HTK is a widely used preservation solution for static cold storage in liver transplantation. The present study was to investigate the beneficial effect of warm HTK donor pretreatment on liver preservation.
  
  
  METHODS
  Male inbred Wistar rats (weighing 230-260 g) served as donors and recipients (n=6/group). Donors of treatment groups received i.v. 0.01 mL/g body weight (BW) warm (21 degree centigrade) HTK systemically 15 minutes prior to cold perfusion. Control groups received 0.01 mL/g BW warm (21 degree centigrade) NaCl 0.9%. Following pretreatment, donors were flushed with 4 degree centigrade cold HTK, livers were explanted and stored in 4 degree centigrade HTK for six hours. Thereafter orthotopic liver transplantation was performed. Recipients were harvested four hours, two and five days after reperfusion and blood and liver tissue samples were obtained. Blood samples were analyzed for AST, ALT, lactate dehydrogenase and bilirubin. Liver histological analysis as well as tissue analysis for pro-MMP2, MMP2 and pro-MMP9 using zymography was conducted.
  
  
  RESULTS
  Treatment groups showed significantly lower ALT and lactate dehydrogenase levels as well as significantly lower activities of pro-MMP2, MMP2 and pro-MMP9. Histological analysis revealed only minor damage in all groups.
  
  
  CONCLUSIONS
  The new concept of warm HTK pretreatment significantly reduced ischemia-reperfusion injury. The reduced ischemia-reperfusion injury was due to MMP inhibition. Warm HTK donor pretreatment is easy to handle and could further improve HTK's potency in liver preservation.
authors.affiliation: Allgemein-, Visceral- & Transplantationschirurgie, Charite Campus Virchow Klinikum, Berlin 13353, Germany. wenzel.schoening@web.de.
authors.forename: Wenzel
authors.initials: W
authors.lastname: Schoening
authors.forename: Veeravorn
authors.initials: V
authors.lastname: Ariyakhagorn
authors.forename: Thomas
authors.initials: T
authors.lastname: Schubert
authors.forename: Peter
authors.initials: P
authors.lastname: Olschewski
authors.forename: Andreas
authors.initials: A
authors.lastname: Andreou
authors.forename: Peter
authors.initials: P
authors.lastname: Neuhaus
authors.forename: Johann
authors.initials: J
authors.lastname: Pratschke
authors.forename: Gero
authors.initials: G
authors.lastname: Puhl
mesh_terms: D061605:Administration, Intravenous; D000818:Animals; D015415:Biomarkers / Q000097:blood; D050377:Cold Ischemia / Q000009:adverse effects*; D004334:Drug Administration Schedule; D004792:Enzyme Precursors / Q000378:metabolism; D018093:Gelatinases / Q000378:metabolism; D005947:Glucose / Q000008:administration & dosage; D006498:Hepatectomy; D008099:Liver / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology / Q000601:surgery*; D016031:Liver Transplantation / Q000009:adverse effects / Q000379:methods*; D008297:Male; D008353:Mannitol / Q000008:administration & dosage; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D009926:Organ Preservation / Q000009:adverse effects / Q000379:methods*; D019188:Organ Preservation Solutions / Q000008:administration & dosage*; D011189:Potassium Chloride / Q000008:administration & dosage; D011343:Procaine / Q000008:administration & dosage; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000097:blood / Q000209:etiology / Q000473:pathology / Q000517:prevention & control*; D013696:Temperature; D013997:Time Factors
chemical_list: D015415:Biomarkers; C039984:Bretschneider cardioplegic solution; D004792:Enzyme Precursors; D019188:Organ Preservation Solutions; D008353:Mannitol; D011343:Procaine; D011189:Potassium Chloride; D018093:Gelatinases; C120487:pro-matrix metalloproteinase 9; C069860:progelatinase; D020778:Matrix Metalloproteinase 2; C522363:Mmp2 protein, rat; D020780:Matrix Metalloproteinase 9; C572337:Mmp9 protein, rat; D005947:Glucose