title: Hydroxyectoine ameliorates preservation injury in deceased after cardiac death donors in experimental liver grafts.
abstract: BACKGROUND
  Due to the drastic shortage of organ donors, clinicians are increasingly considering the use of deceased after cardiac death donors (DCD). Compatible solutes like Ectoine and Hydroxyectoine are produced by extremophilic bacteria as a cell protectant to survive in harsh environments. We hypothesized that the addition of Hydroxyectoine to Histidine-Tryptophan-Ketoglutarate solution (HTK) could ameliorate cold ischemic preservation injury of DCD livers.
  
  
  METHODS
  Rat livers were harvested from male Wistar rats weighing 250-300 g. Three experimental groups (n=5 per group) were studied: (1) CONTROLS: cold static storage in HTK for 24 h, (2) DCD: 30-min warm ischemia time and 24-h cold static storage in HTK, and (3) DCD+Hydroxyectoine: like DCD, but with 24-h cold static storage in HTK+Hydroxyectoine. Viability of the livers was assessed after 24 h of preservation by isolated perfusion for 45 min with oxygenated Krebs-Henseleit buffer solution.
  
  
  RESULTS
  (mean ±SEM, Control vs. DCD vs. DCD+Hydroxyectoine) Parenchymal enzyme release was significantly lower in DCD+Hydroxyectoine compared to DCD (AST: 9±0.54; 56.8±2.05; 32.2±7.25 U/L, ALT: 9.5±0.5; 37.75±9.6; 17.5±4.17 U/L). Bile production at the end of 45 min reperfusion was significantly higher in DCD+Hydroxyectoine (5.16±1.32; 1.36±0.34; 10.75±2.24 µL/g liver weight/45 min). Malondialdehyde values were significantly lower in DCD+Hydroxyectoine (0.8±0.09, 1.14±0.18, 0.77±0.08 nmol/mL). Intercellular adhesion molecule-1 showed significantly lower values in DCD+Hydroxyectoine (219.07±51.79, 431.9±35.70, 205.2±37.71 pg/mL) and the portal venous pressure at 45 min was lower compared to DCD (20.41±0.12, 27.47±0.45, 22.08±0.78 mmHg).
  
  
  CONCLUSIONS
  Our data provide evidence for the beneficial role of Hydroxyectoine-modified HTK solution for the preservation of DCD livers compared to HTK.
authors.affiliation: Institute for Laboratory Animal Science and Experimental Surgery, University Hospital RWTH Aachen, Aachen, Germany.
authors.forename: Pramod
authors.initials: P
authors.lastname: Kadaba Srinivasan
authors.affiliation: Institute for Laboratory Animal Science and Experimental Surgery, University Hospital RWTH Aachen, Aachen, Germany.
authors.forename: Ngwi
authors.initials: N
authors.lastname: Fet
authors.affiliation: Department of Anesthesiology, University Hospital RWTH Aachen, Aachen, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Bleilevens
authors.affiliation: Institute for Laboratory Animal Science and Experimental Surgery, University Hospital RWTH Aachen, Aachen, Germany.
authors.forename: Mamdouh
authors.initials: M
authors.lastname: Afify
authors.affiliation: Institute for Laboratory Animal Science and Experimental Surgery, University Hospital RWTH Aachen, Aachen, Germany.
authors.forename: Benedict
authors.initials: B
authors.lastname: Doorschodt
authors.affiliation: Department of Hepatobiliary, Pancreas and Transplant Surgery, Kyoto University, Kyoto, Japan.
authors.forename: Shintaro
authors.initials: S
authors.lastname: Yagi
authors.affiliation: Kekulé Institute, LIMES Membrane Biology and Lipid Biochemistry Unit, University of Bonn, Bonn, Germany.
authors.forename: Gerhild
authors.initials: G
authors.lastname: van Echten-Deckert
authors.affiliation: Institute for Laboratory animal science and experimental surgery, University Hospital RWTH Aachen University, Aachen, Germany.
authors.forename: René Hany
authors.initials: RH
authors.lastname: Tolba
mesh_terms: D000599:Amino Acids, Diamino / Q000494:pharmacology*; D000818:Animals; D001646:Bile / Q000378:metabolism; D050377:Cold Ischemia; D019610:Cytoprotection / Q000187:drug effects; D003643:Death; D005947:Glucose / Q000494:pharmacology; D006085:Graft Survival / Q000187:drug effects*; D006820:Hyaluronic Acid / Q000378:metabolism; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D016031:Liver Transplantation; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D019188:Organ Preservation Solutions / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000378:metabolism / Q000517:prevention & control*; D000637:Transaminases / Q000378:metabolism; D014325:Tromethamine / Q000494:pharmacology; D052096:Warm Ischemia
chemical_list: D000599:Amino Acids, Diamino; C074097:Krebs-Henseleit solution; D019188:Organ Preservation Solutions; C121557:hydroxyectoine; D014325:Tromethamine; D018799:Intercellular Adhesion Molecule-1; D008315:Malondialdehyde; D006820:Hyaluronic Acid; D000637:Transaminases; D005947:Glucose