Chronic fetal hypoxemia stimulates erythropoiesis and may result in a redistribution of fetal iron from plasma into erythrocytes. We studied the response of fetal plasma erythropoietin (Ep) to hypoxemia, the role of Ep in stimulating erythropoiesis in utero, and the effect of augmented erythropoiesis on fetal plasma Ep and iron and tissue cytochrome c concentrations in 19 chronically instrumented late-gestation fetal sheep. The fetuses were stimulated to produce 28 erythropoietic responses after exposure to 1) acute hypoxemia (1-5 days), 2) chronic hypoxemia (greater than 7 days), and/or 3) administration of 1,500 U recombinant human Ep concurrently during normoxemia. Plasma Ep peaked less than 12 h after the onset of hypoxemia or Ep bolus. Plasma iron decreased 24-48 h later and returned to baseline 48-96 h after normalization of Ep levels to baseline. The plasma iron response was directly related to the erythropoietin stimulus (r = 0.79, P less than 0.001) and inversely related to liver iron concentration at death (r = -0.84, P less than 0.001). Nine fetuses with depleted liver iron concentrations at autopsy had significantly lower heart and skeletal muscle iron concentrations compared with animals with 10% of control liver iron remaining. Skeletal muscle and heart iron and cytochrome c concentrations were significantly correlated. Ep has a potent biological effect on fetal erythropoiesis and iron metabolism. Augmented fetal erythropoiesis, mediated by Ep, results in decreased plasma iron, hepatic storage iron, and skeletal and cardiac muscle iron and cytochrome c. The model potentially explains the iron abnormalities found in newborn infants after fetal hypoxia.
Total urinary nitrogen (TUN) determinations for nitrogen-balance studies were traditionally performed by the Kjeldahl method, but this method is laborious, hazardous, prone to error, and no longer widely available in most clinical laboratories. During the last several decades, urinary urea nitrogen (UUN) determinations have replaced TUN as an index of urinary nitrogen excretion in many clinical laboratories, owing to its ease of determination, decreased cost, and wide availability. However, the validity of using UUN for estimating nitrogen loss has been questioned in many disease states, owing to wide variations in the proportional amount of urea found in TUN. Chemiluminescence has been proposed as an alternative to the Kjeldahl method for TUN. TUN values obtained from 24-h urine collections measured by both micro-Kjeldahl (x) and Pyrochemiluminescence (y) (Antek Instruments, Inc.) techniques were comparable by linear regression analysis: n = 97; r = 0.996; r2 = 0.992; y = 1.048x - 0.606; P less than 0.001. Automated induction of samples and calculation of results allows up to 42 samples to be run unattended. This dramatically reduces labor and overall costs for TUN determinations, while providing a more accurate and economical assessment of nitrogen excretion than UUN in a clinical setting.
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