title: Erythropoietin as additive of HTK preservation solution in cold ischemia/reperfusion injury of steatotic livers.
abstract: BACKGROUND
  Organ shortage in liver transplantation has justified usage of marginal donor livers to expand the donor organ pool. The particular susceptibility of steatotic livers to I/R injury necessitates optimal preservation conditions in order to minimize preservation-reperfusion injury for successful transplantation.
  
  
  METHODS
  The effect of erythropoietin (EPO) as additive to HTK preservation solution was studied in a mouse model. Lean and steatotic livers were harvested, stored for 24 h in 4°C HTK solution containing either EPO or saline and reperfused for 2 h with 37°C Krebs-Henseleit buffer. Livers without cold storage served as sham controls.
  
  
  RESULTS
  Flushing of livers upon cold storage revealed a transaminase release, which was 2- to 10-fold higher in steatotic versus lean livers. EPO was effective in reducing the enzyme release to 50% in steatotic but not in lean livers. EPO prevented cold storage-induced denudation of the endothelial lining in steatotic livers, but aggravated it in lean livers. During reperfusion, steatotic livers presented with lower oxygen consumption and higher enzyme release than lean livers. In all livers, parameters of reperfusion injury remained unaffected by EPO. Expression of UCP2 was found markedly higher in steatotic livers. After I/R, steatotic livers revealed a significant drop of UCP2, whereas expression in lean livers was only slightly affected. EPO diminished Erk phosphorylation to almost the same extent in both mouse strains.
  
  
  CONCLUSIONS
  Fortification of the preservation solution by EPO ameliorates cold ischemic injury of steatotic livers and may thus be considered for use as an adjunctive agent to increase the success of transplanting steatotic livers.
authors.affiliation: Institute for Experimental Surgery, University of Rostock, Rostock, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Eipel
authors.forename: Ulrike
authors.initials: U
authors.lastname: Hübschmann
authors.forename: Kerstin
authors.initials: K
authors.lastname: Abshagen
authors.forename: Klaus F
authors.initials: KF
authors.lastname: Wagner
authors.forename: Michael D
authors.initials: MD
authors.lastname: Menger
authors.forename: Brigitte
authors.initials: B
authors.lastname: Vollmar
mesh_terms: D000818:Animals; D003080:Cold Temperature; D004195:Disease Models, Animal; D004921:Erythropoietin / Q000494:pharmacology / Q000627:therapeutic use*; D005234:Fatty Liver / Q000209:etiology / Q000378:metabolism* / Q000473:pathology; D005260:Female; D005947:Glucose / Q000494:pharmacology / Q000627:therapeutic use; D007473:Ion Channels / Q000378:metabolism; D008099:Liver / Q000098:blood supply* / Q000187:drug effects / Q000378:metabolism*; D016031:Liver Transplantation; D008297:Male; D008353:Mannitol / Q000494:pharmacology / Q000627:therapeutic use; D051379:Mice; D008815:Mice, Inbred Strains; D008820:Mice, Obese; D024101:Mitochondrial Proteins / Q000378:metabolism; D020929:Mitogen-Activated Protein Kinase Kinases / Q000378:metabolism; D009765:Obesity / Q000150:complications; D019188:Organ Preservation Solutions / Q000494:pharmacology / Q000627:therapeutic use; D011189:Potassium Chloride / Q000494:pharmacology / Q000627:therapeutic use; D011343:Procaine / Q000494:pharmacology / Q000627:therapeutic use; D017467:Receptors, Erythropoietin / Q000378:metabolism; D015427:Reperfusion Injury / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D015398:Signal Transduction / Q000187:drug effects; D013851:Thinness / Q000378:metabolism; D000071246:Uncoupling Protein 2
chemical_list: C039984:Bretschneider cardioplegic solution; D007473:Ion Channels; D024101:Mitochondrial Proteins; D019188:Organ Preservation Solutions; D017467:Receptors, Erythropoietin; C000604390:Ucp2 protein, mouse; D000071246:Uncoupling Protein 2; D004921:Erythropoietin; D008353:Mannitol; D011343:Procaine; D011189:Potassium Chloride; D020929:Mitogen-Activated Protein Kinase Kinases; D005947:Glucose