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

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)- 1a 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- 1a 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- 1a 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..