Oxygen Transport in Congenital Heart Disease: Influence of Fetal Hemoglobin, Red Cell pH, and 2,3-Diphosphoglycerate

Abstract

Extract: In 48 individuals (age 1 day to 13 years) with congenital heart disease, blood oxygen transport function was studied in order to evaluate adaptive changes in shunt hypoxemia and to investigate the in vivo regulation of erythrocyte 2,3-diphosphoglycerate concentration (RBC 2,3-DPG) in the presence of fetal hemoglobin (HbF). Arterial pO₂ and oxygen content, oxygen capacity, acid base status, oxygen affinity, HbF fraction, plasma pH, red cell pH, and RBC 2,3-DPG were determined. During the first 50 days of life values of standard P₅₀ (stdP₅₀) (37°, pH7.4), actual in vivo P₅₀ (actP₅₀), RBC 2,3-DPG, O₂ capacity, arterial plasma pH, and red cell pH were scattered around the normal range, although tending to low values for stdP₅₀ and arterial plasma pH and to high values for O₂ capacity. After the third month, stdP₅₀ actP⁵⁰, RBC 2,3-DPG, O₂ capacity, and red cell pH were found to be elevated. Plasma pH and actP₅₀ were scattered around the normal range (Figs. 1 and 2). Intraerythrocytic pH in hypoxemic infants was increased compared with normal children when related to plasma pH (Fig. 3). A close to normal intraerythrocytic pH was therefore found in the hypoxemic infants with low plasma pH, and an increased intraerythrocytic pH in the hypoxemic children with normal plasma pH (Fig. 1). A significant negative correlation exists between erythrocyte H⁺ ion and 2,3-DPG concentration (Fig. 5); regression constants derived from data at high (mean 47%) and low (mean 9%) fractions of HbF are not significantly different (Regression Equations 8 and 11 in Table 1). Thus, the known difference in 2,3-DPG binding to fetal or adult deoxyhemoglobin does not measurably influence the erythrocyte 2,3-DPG concentration, indicating that in vivo the 2,3-DPG synthesis in hypoxia is virtually regulated by the erythrocyte pH, which in turn is determined by plasma pH and the oxygenation state of hemoglobin. Speculation: In young infants and older children with cyanotic heart disease an identical negative correlation between the concentrations of 2,3-DPG and hydrogen ions within the erythrocyte was found. The in vivo regulation of 2,3-DPG synthesis thus appears to be controlled by the erythrocyte pH which, in turn, is determined by plasma pH and oxygen saturation of hemoglobin. Apparently the well established difference of 2,3-DPG binding to fetal or adult deoxyhemoglobin does not measurably influence the erythrocyte 2,3-DPG concentration, indicating that in vivo a relief of product inhibition of the diphosphoglycerate mutase does not contribute significantly to the regulation of 2,3-DPG synthesis in hypoxemia.