EFFECT OF HYPOXEMIA ON TISSUE GLYCOGEN-CONTENT AND GLYCOLYTIC ENZYME-ACTIVITIES IN FETAL SHEEP

We have tested the hypothesis that prolonged fetal hypoxemia causes a reduction in glycogenolytic enzyme activities and/or a depletion of fe tal glycogen stores. We compared the effects of short (4 h) and prolon ged (24 h) periods of reduced maternal uterine blood flow (RUBF) on gl ycogen content and on the activities of glucose-6-phosphatase (G-6-Pas e), glycogen phosphorylase (GPase), and glycogen synthase (GSase) in s elected fetal tissues. RUBF was reduced in 10 pregnant sheep at 135 da ys of gestation (term similar to 146 days) for either 4 h (n = 5) or 2 4 h (n = 5); 5 other fetuses were used as controls. During RUBF, fetal SaO(2) was decreased from 61.6 +/- 3.9 to 22.0 +/- 1.4% at 4 h and to 26.7 +/- 1.2% at 24 h. Hepatic glycogen content was significantly red uced at 4 h of RUBF, but was not reduced further at 24 h. Fetal liver GPase (active and total enzyme activity) and G-6-Pase activities were reduced at 4 h of RUBF but tended to return toward control values at 2 4 h. Similarly, hepatic GSase activity tended to decrease at 4 h of RU BF, although the reduction was not quite significant (P = 0.08). We co nclude that RUBF causes a reduction of fetal glycogen stores and a red uction in G-6-Pase and GPase activity at 4 h. Fetal tissue glycogen co ntents were not reduced further at 24 h, compared with 4 h of RUBF, wh ich indicates that fetal glycogenolysis is reduced during this time, p robably because of the inhibition of GPase and G-6-Pase. It is not kno wn why the activities of these enzymes are reduced during prolonged RU BF, when circulating epinephrine and norepinephrine concentrations are high.