Umbilical Uptake Research Articles

The rate of amino acid nitrogen and total nitrogen accumulation in the fetal lamb.

AbstractTotal body water and nitrogen concentrations were determined for whole body homogenates of 18 fetal lambs. Nitrogen concentration averaged 10.5 ± 0.1 mg nitrogen/100 mg dry tissue. Amino acid represented approximately 82% of the total nitrogen and 55% of the total carbon content of the fetus. The carbon/nitrogen ratio attributable to amino acids decreased from 3.42 at 66 days to 3.06 at term. Total amino acid concentrations in the whole body homogenates were also determined for 20 amino acids. Cystine and hydroxy-proline concentrations increased significantly (correl. coeff. = 0.78) and markedly with gestation. The branch chain amino acids, leucine, isoleucine, and valine, along with phenylalanine, showed a significant decline in concentration (correl. coeff. ≧ −0.79). From these rates of amino acid and nitrogen accretion the adequacy of the exogenous supply of amino acids and nitrogen to the fetus via the umbilical uptake can be assessed. Calculations of the excess supply of amino acids to the fe...

Effects of gastric nutritional supplementation on fetal umbilical uptake of nutrients.

Intrauterine nutritional supplementation may be of therapeutic benefit to the malnourished, growth-retarded fetus. Using 14 chronically catheterized, third trimester fetal lambs, we evaluated the effects of gastric infusions of amino acids and glucose on umbilical uptake of alpha-amino nitrogen, glucose, lactate, and oxygen. When amino acids were infused, amino nitrogen was gained through the intestine at an average rate equal to 45% of fetal umbilical uptake of amino nitrogen. There were no consistent changes in umbilical uptake of the measured nutrients, except for a small decrease in umbilical uptake of oxygen (P less than 0.05). No relationship were found between changes in fetal amino nitrogen levels or changes in fetal-maternal amino nitrogen concentration gradients and umbilical uptake of amino nitrogen. When glucose was infused, glucose was absorbed through the intestine at an average rate equal to 42% of fetal umbilical uptake of glucose. There were no changes in umbilical uptake of amino nitrogen, lactate, or oxygen. Umbilical uptake of glucose decreased, however, in inverse proportion to both the glucose infusion rate (P less than 0.005) and the rise in fetal glucose concentration (P less than 0.025). This limited the quantity of glucose that could be gained by the fetus, via gastrointestinal supplementation. During the infusions, we also observed a change in the pattern of fetal lower body blood flow. There was a 12% decrease in the mean umbilical blood flow (P less than 0.005) and a 22% increase in mean intestinal flow (P less than 0.05).

Simultaneous measurements of umbilical uptake, fetal utilization rate, and fetal turnover rate of glucose.

Fetal umbilical glucose uptake was compared with simultaneous measurements of glucose turnover and utilization rates in 12 pregnant sheep, at a mean of 137 days gestational age (range, 118-146 days). Umbilical glucose uptake was calculated by application of the Fick principle. Fetal glucose turnover rate was measured by a primed-constant infusion of [14C]- and [3H]glucose (glucose turnover rate = tracer infusion rate divided by fetal glucose sp act). The calculation of fetal glucose utilization rate required substraction of the loss of tracer to the placenta from the tracer infusion rate, thus defining the net tracer entry into the fetus for direct comparison with the net umbilical glucose uptake. In fed, normoglycemic sheep, these measurements demonstrated statistical equivalence of umbilical glucose uptake rate (4.77 mg.min-1.kg-1 +/- 0.34 SE) and glucose utilization rate ([14C]glucose, 5.58 mg.min-1.kg-1 +/- 0.54 SE; and [3H]glucose, 7.19 mg.min-1.kg-1 +/- 1.24 SE) when tested by two-way analysis of variance (P greater than 0.1). In three fasted, hypoglycemic sheep, the umbilical glucose uptake rate fell to 1.43 mg.min-1.kg-1 +/- 0.56 SE, which was considerably lower than the simultaneous glucose utilization rate ([14C]glucose, 4.78 mg.min-1.kg-1 +/- 0.48 SE; and [3H]glucose, 6.81 mg.min-1.kg-1 +/- 2.19 SE). Thus, in the normoglycemic, late-gestation fetal lamb, there appears to be little glucogenesis, whereas glucogenesis may become significant during fasting-induced fetal hypoglycemia.

Uterine uptake of amino acids throughout gestation in the unstressed ewe

The uterine uptake of 21 amino acids was determined in chronically catheterized ewes from 35 to 145 days of gestation. Total uptake of amino acids increased as gestation progressed as described by the equation: Q (mmoles/kg · day) = 0.19 gestational age (days) + 0.30. We were unable to detect a statistically significant correlation of uterine A-V concentration difference and gestational age for most amino acids. The uptakes of only eight amino acids contributed to the total increase (arginine, glutamine, valine, leucine, ornithine, isoleucine, tyrosine, phenylalanine). The amino acids which made the largest contribution to uterine uptake are similar to those which furnish the largest contributions to umbilical uptake previously reported, except for glycine, which exhibits significant umbilical uptake, but no uterine uptake. Glutamate, which is removed by the placenta from the umbilical circulation, exhibited no significant uterine uptake nor production. The total amino acid nitrogen uptake by the uterus extrapolated to 130 days’ gestation, 1.20 gm/kg fetal weight · day, closely approximates the previously reported value for umbilical amino acid nitrogen uptake at 130 days. Comparison of the individual amino acids removed from the uterine circulation with those which enter the umbilical circulation, however, suggests that metabolic conversions which involve glutamate and glycine occur in the placenta.

Effect of uterine artery insulin infusions on umbilical glucose uptake in sheep.

Although glucose is an important fuel for fetal oxidative metabolism, regulation of its availability to the mammalian fetus is poorly understood. This study was performed to determine the effect of infusions of insulin into the uterine arterial circulation on umbilical uptake of glucose in chronically instrumented, unstressed sheep. Twenty-eight determinations of umbilical glucose uptake and diffusion clearance of glucose by the placenta were made in four ewes. Immediately following a control study during which saline was infused into the uterine artery, porcine regular insulin diluted in saline was infused at 0.05 to 8.1 mU/min . kg uterine weight for 20--30 min and the determinations were repeated. Subsequent studies were performed at the conclusion of additional infusions of insulin to a maximum of 21.6 mU/min . kg. There was a significant increase in umbilical glucose uptake during initial insulin infusions (4.47 +/- 0.6 mg/min . kg fetus) compared to the control studies (3.08 +/- 0.6 mg/min . kg) associated with an increase in diffusion clearance (13.8 +/- 1.9 ml/min . kg fetus vs. 8.99 +/- 1.8 ml/min . kg). When the total cumulative dose of exogenous insulin, It, was 162 mU/kg uterine weight or less, the umbilical uptake of glucose, Q, may be expressed as a function of maternal arterial blood glucose concentration in milligrams per dl, [A], and of It.

Principal substrates of fetal metabolism.

Principal substrates of fetal metabolism.

176 FETAL SHEEP PLASMA INSULIN CONCENTRATION AND UMBILICAL LACTATE UPTAKE

To determine the relationship between fetal and maternal plasma insulin concentrations (If, Im) and umbilical uptake of glucose (Qg) and lactate (Ql) in sheep, 6 ewes of 120-130 days gestation were prepared with indwelling catheters in the umbilical vein, fetal pedal artery and vein, and maternal uterine and femoral arteries. Fed state Qg, Ql, If, and I were determined at intervals from the 2nd to the 11th postoperative day (POD). Qg and Ql were determined by the Fick principle employing steady state diffusion of antipyrine to determine umbilical blood flow. Studies were performed before (control n=15) and after (n=15) the perfusion of the uterine artery with ovine insulin 7.5 mU/kg ewe/30 min. Insulin was measured by radioimmunoassay. Results: Control If and Im in μ U/ml increased with increasing POD as described by the following regression equations: If = 0.76 POD + 3.74, (F ratio, p < .025), and Im = 1.86 POD + 8.61, (p < .05). Uterine artery insulin infusion increased Im but did not affect If or Ql. The postoperative increase in If from 5.5-16.0μ μ U/ml was associated with a decrease in Ql in mM/min/kg fetus: Ql = -0.004 If + 0.072 (p < .025). Qg was unrelated to POD, Ql, or If. Conclusions: These studies (1) confirm the lack of ovine insulin transfer across the ovine placenta in vivo, (2) demonstrate increasing Im and If for as long as 11 days after surgery and resumption of maternal nutrition, and (3) show that umbilical lactate uptake is inversely related to fetal plasma insulin concentration, but is independent of umbilical glucose uptake and of maternal plasma insulin concentration.

Umbilical uptake of amino acids in the unstressed fetal lamb.

The whole blood concentrations of 22 amino acids were measured in a chronic, unstressed fetal lamb preparations. Samples were taken daily from the umbilical artery, umbilical vein, and maternal artery over the latter quarter of gestation. 73 sets of samples (from the umbilical artery and vein and the maternal artery) from 13 animals were analyzed for amino acid levels. Oxygen contents were determined simultaneously in 48 sets (umbilical artery and vein) to relate fetal oxygen consumption to amino acid uptake via the umbilical circulation. The results indicate that there is no umbilical uptake of the acidic amino acids, glutamate and aspartate; there is, in fact, a net flux of glutamate out of the fetus into the placenta. As both of these amino acids are major constituents of body proteins, the data indicate that they are formed within the fetus. The umbilical uptake of some neutral and basic amino acids (e.g., valine, leucine, isoleucine, arginine, phenylalanine, and tyrosine) is in considerable excess of estimated growth requirements, suggesting that some amino acids undergo extensive transamination and oxidative degradation in the fetus. Finally, the net uptake of nitrogen, carbon, and calories by the growing ovine fetus in the form of amino acids, glucose, and lactate is compared to estimated requirements as determined in previous studies.

Umbilical V-A differences of acetoacetate and beta-hydroxybutyrate in fed and starved ewes.

Conclusions(a) Starvation in the pregnant ewe is associated with an increase in maternal blood concentrations of acetoacetate and β-hydroxybutyrate.(b) Despite elevated maternal concentrations of acetoacetate, the umbilical venous-arterial blood acetoacetate difference does not change during maternal starvation. However, rising maternal levels of β-hydroxybutyrate are associated with increasing umbilical venous-arterial β-hydroxybutyrate concentration differences.(c) Neither acetoacetate nor β-hydroxybutyrate umbilical uptake is used by the sheep fetus as a major fuel of aerobic metabolism, even during maternal starvation.

The effect of estrogen on fetal oxygenation

In 6 pregnant ewes and 2 goats the umbilical uptake of oxygen was measured before and after the administration of estrogen. In 5 animals with an umbilical uptake of oxygen of less than 8 ml. per kilogram per minute the administration of estrogen resulted in higher oxygen uptakes. It seems probable that the improved fetal oxygenation is the result of increased uterine blood flow.

THE SUPPLY OF O2 TO THE PRIMATE FETUS WITH TWO DIFFERENT O2 TENSIONS AND ANESTHETICS

Umbilical blood flows and fetal oxygen uptakes were measured in 18 pregnant Macaca mulatta monkeys at maternal arterial O2 tensions of 107 mm Hg ± 14 mm Hg. The average umbilical blood flow was 212 cc.min−1.kg−1 and the average fetal oxygen consumption was 7.73 cc.min−1.kg−1. In 8 of these animals the average uterine blood flow was 213 cc.min−1.kg−1 and the average uterine oxygen uptake was 10.85 cc.min−1.kg−1. Seventy-four per cent (8.02 cc.min−1.kg−1) of this oxygen was taken up by the fetus and 26% (2.83 cc.min−1.kg−1 by the uteroplacental tissue. Elevated maternal arterial PO2 tensions (257 ± 59) did not result in a statistically significant increase or decrease in the umbilical or uterine blood flows or oxygen uptake in nonasphyxiated primate fetuses. The oxygen tension in the fetal umbilical vein increased significantly (P < 0.025). The results were similar under anesthesia with either halothane or succinylcholine.