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Metabolic shift in liver: Correlation between perfusion temperature and hypoxia inducible factor-1α

2015; Baishideng Publishing Group; Volume: 21; Issue: 4 Linguagem: Inglês

10.3748/wjg.v21.i4.1108

2219-2840

Andrea Ferrigno, Laura Giuseppina Di Pasqua, Alberto Bianchi, Plinio Richelmi, Mariapia Vairetti,

Liver Disease Diagnosis and Treatment

AIM: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 ℃.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 ℃ 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 ℃ (5.63 ± 0.76 vs 527.69 ± 45.27 mU/min per g, respectively, P s < 0.01).After 6 h, tissue ATP was significantly higher in livers perfused at 10 and 20 ℃ than in livers perfused at 30 and 37 ℃ (0.89 ± 0.06 and 1.16 ± 0.05 vs 0.57 ± 0.09 and 0.33 ± 0.08 nmol/ mg, respectively, P s < 0.01).No sign of hypoxia was observed at 10 and 20 ℃, as highlighted by low lactate release respect to livers perfused at 30 and 37 ℃ (121.4 ± 12.6 and 146.3 ± 7.3 vs 281.8 ± 45.3 and 1094.5 ± 71.7 nmol/mL, respectively, P s < 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, P s < 0.05) and protein (3.72 ± 0.16 and 3.65 ± 0.06 vs 4.43 ± 0.41 and 6.44 ± 0.82, respectively, P s < 0.05) expression. CONCLUSION:Livers perfused at 10 and 20 ℃ show no sign of liver injury or anaerobiosis, in contrast to livers perfused at 30 and 37 ℃.