title: Metabolic shift in liver: correlation between perfusion temperature and hypoxia inducible factor-1α.
abstract: OBJECTIVE
  To study at what temperature the oxygen carried by the perfusate meets liver requirements in a model of organ perfusion.
  
  
  METHODS
  In this study, we correlated hypoxia inducible factor (HIF)-1α expression to the perfusion temperature and the hepatic oxygen uptake in a model of isolated perfused rat liver. Livers from Wistar rats were perfused for 6 h with an oxygenated medium at 10, 20, 30 and 37 °C. Oxygen uptake was measured by an oxygen probe; lactate dehydrogenase activity, lactate release and glycogen were measured spectrophotometrically; bile flow was gravitationally determined; pH of the perfusate was also evaluated; HIF-1α mRNA and protein expression were analyzed by real time-polymerase chain reaction and ELISA, respectively.
  
  
  RESULTS
  Livers perfused at 10 and 20 °C showed no difference in lactate dehydrogenase release after 6 h of perfusion (0.96±0.23 vs 0.93±0.09 mU/min per g) and had lower hepatic damage as compared to 30 and 37 °C (5.63±0.76 vs 527.69±45.27 mU/min per g, respectively, Ps<0.01). After 6 h, tissue ATP was significantly higher in livers perfused at 10 and 20 °C than in livers perfused at 30 and 37 °C (0.89±0.06 and 1.16±0.05 vs 0.57±0.09 and 0.33±0.08 nmol/mg, respectively, Ps<0.01). No sign of hypoxia was observed at 10 and 20 °C, as highlighted by low lactate release respect to livers perfused at 30 and 37 °C (121.4±12.6 and 146.3±7.3 vs 281.8±45.3 and 1094.5±71.7 nmol/mL, respectively, Ps<0.02), and low relative HIF-1α mRNA (0.40±0.08 and 0.20±0.03 vs 0.60±0.20 and 1.47±0.30, respectively, Ps<0.05) and protein (3.72±0.16 and 3.65±0.06 vs 4.43±0.41 and 6.44±0.82, respectively, Ps<0.05) expression.
  
  
  CONCLUSIONS
  Livers perfused at 10 and 20 °C show no sign of liver injury or anaerobiosis, in contrast to livers perfused at 30 and 37 °C.
authors: Andrea Ferrigno, Laura Giuseppina Di Pasqua, Alberto Bianchi, Plinio Richelmi, Mariapia Vairetti, Unit of Cellular and Molecular Pharmacology and Toxicology, Department of Internal Medicine and Therapeutics, University of Pavia, Pavia 27100, Italy.
authors: Andrea
authors: A
authors: Ferrigno
authors: Andrea Ferrigno, Laura Giuseppina Di Pasqua, Alberto Bianchi, Plinio Richelmi, Mariapia Vairetti, Unit of Cellular and Molecular Pharmacology and Toxicology, Department of Internal Medicine and Therapeutics, University of Pavia, Pavia 27100, Italy.
authors: Laura Giuseppina
authors: LG
authors: Di Pasqua
authors: Andrea Ferrigno, Laura Giuseppina Di Pasqua, Alberto Bianchi, Plinio Richelmi, Mariapia Vairetti, Unit of Cellular and Molecular Pharmacology and Toxicology, Department of Internal Medicine and Therapeutics, University of Pavia, Pavia 27100, Italy.
authors: Alberto
authors: A
authors: Bianchi
authors: Andrea Ferrigno, Laura Giuseppina Di Pasqua, Alberto Bianchi, Plinio Richelmi, Mariapia Vairetti, Unit of Cellular and Molecular Pharmacology and Toxicology, Department of Internal Medicine and Therapeutics, University of Pavia, Pavia 27100, Italy.
authors: Plinio
authors: P
authors: Richelmi
authors: Andrea Ferrigno, Laura Giuseppina Di Pasqua, Alberto Bianchi, Plinio Richelmi, Mariapia Vairetti, Unit of Cellular and Molecular Pharmacology and Toxicology, Department of Internal Medicine and Therapeutics, University of Pavia, Pavia 27100, Italy.
authors: Mariapia
authors: M
authors: Vairetti
mesh_terms: D000818:Animals; D003080:Cold Temperature; D004734:Energy Metabolism; D006003:Glycogen / Q000378:metabolism; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000235:genetics / Q000378:metabolism*; D066298:In Vitro Techniques; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D019344:Lactic Acid / Q000378:metabolism; D008099:Liver / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008297:Male; D009926:Organ Preservation / Q000009:adverse effects / Q000379:methods*; D019188:Organ Preservation Solutions / Q000378:metabolism / Q000494:pharmacology*; D010100:Oxygen / Q000378:metabolism*; D010477:Perfusion / Q000009:adverse effects / Q000379:methods*; D012333:RNA, Messenger / Q000378:metabolism; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000209:etiology / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D013997:Time Factors; D014022:Tissue Survival
chemical_list: C497444:Hif1a protein, rat; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D019188:Organ Preservation Solutions; D012333:RNA, Messenger; D019344:Lactic Acid; D006003:Glycogen; D007770:L-Lactate Dehydrogenase; D010100:Oxygen
keywords: Anaerobiosis; Hypoxia inducible factor-1α; Ischemia; Liver transplantation; Machine perfusion
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