Hepatic Metabolism During Acute Hypoxia in Fetal Lambs † 273

Abstract

The fetal liver is a principal organ for the metabolic response to acute hypoxia in-utero. To better understand its biochemical role, we simultaneously studied fetal and hepatic changes in blood flow, oxygen consumption, and lactate and pyruvate metabolism during normal and hypoxic conditions.Methods: In 7 pregnant ewes, sampling catheters were placed across the umbilical and fetal left hepatic circulations. After recovery, indocyanine green (ICG) and tritiated water were infused at a constant rate into the fetus for measurement of left hepatic blood flow and umbilical blood flow, respectively. Each study day, blood samples were taken for ICG, tritiated water, oxygen, lactate, and pyruvate concentrations under normal conditions and hypoxia induced by occlusion of the maternal common internal iliac artery for 30 minutes. Using the Fick principle, substrate uptake for both control and hypoxia was calculated using the concentration difference across the left hepatic and umbilical circulations. Animals were recovered for at least 24 hours prior to the next study day, and each animal was studied no more than 3 times. At autopsy, catheter placement was verified and the fetal liver transected into left and right hepatic lobes and weighed. Paired samples were analyzed by paired 2-tailed t-test. Results: 17 paired control/hypoxia studies were obtained in 7 animals. Values are mean(±SD) control versus hypoxia. Fetal arterial oxygen content was 2.60(0.50) and decreased to 1.21(0.26) mM (p<0.001) with occlusion. Umbilical blood flow increased from 223.11(27.16) to 294.60(52.09) ml/min/kg(p<0.001). Left hepatic blood flow was 371.10(127.88) and 405.85(199.68) ml/min/gm (NS). Fetal oxygen uptake decreased, 0.33(0.03) to 0.24(0.04) uM/min/gm (p<0.001). Left hepatic oxygen uptake did not change, 1.61(0.32) versus 1.63(0.28) uM/min/gm (NS). Fetal lactate uptake 0.021(0.008) went to production (-)0.022(0.033) uM/min/gm (p<0.001). Left hepatic lactate uptake increased, 0.515(0.116) to 0.827(0.331) uM/min/gm (p<0.001). Fetal pyruvate production increased, (-)0.001(0.001) to (-)0.003(0.002) uM/min/gm, as did left hepatic pyruvate production, (-)0.057(0.024) to (-)0.156(0.043) uM/min/gm(p<0.001). Conclusions: The fetus maintained a constant left hepatic oxygen consumption and blood flow in the presence of acute hypoxia and decreased fetal oxygen uptake. In addition, during fetal lactate production, the fetal liver increased lactate consumption while increasing pyruvate production. We speculate a biochemical exchange of lactate for pyruvate occurs as the liver works to restore metabolic homeostasis.