The increase in fetal hemoglobin synthesis in the fetal lamb during hyperglycemic hypoxemia

To determine whether fetal hypoxemia induced by hyperglycemia has any effect on the proportions of fetal and adult hemoglobin synthesized during fetal development, hemoglobin synthesis was determined after a period of hyperglycemic hypoxemia in the fetal lamb. These experiments were carried out at a time in gestation during the switch from fetal to adult hemoglobin. Twelve catheterized fetal sheep were included in this study. Seven were made hyperglycemic by glucose infusions during 5 days (group I) and five were control animals (group II) that received saline solution infusions (0.45 gm/dl). In group I, glycemia increased from 14.7 +/- 5.0 to 54.6 +/- 16.4 mg/dl (p less than 0.001), whereas oxygen content decreased from 8.5 +/- 1.7 to 6.4 +/- 2.2 ml/dl (p less than 0.01). Red blood cells obtained before and after 5 days of glucose or saline solution infusions were incubated in an amino acid mixture containing 14C-leucine. The hemoglobins were then subjected to polypeptide chain elution with carboxymethyl cellulose chromatography. The amount of fetal hemoglobin synthesized was determined by the ratio of radioactive gamma-chain to total of radioactive non-alpha-chains. The data demonstrated that the hyperglycemic fetus synthesizes more fetal hemoglobin than expected for the period of fetal development (78.0% +/- 10.9% versus 59.8% +/- 11.3%, p less than 0.02).