Erythrocyte 2,3-diphosphoglycerate and erythropoietic activity in rabbits with severe bleeding anaemia superimposed in the early post-natal fall in haemoglobin

Erythrocyte 2,3-diphosphoglycerate (2,3-DPG), whole blood haemoglobin (Hb), haematocrit (Hct), mean corpuscular haemoglobin concentration (MCHC) and reticulocyte percentage (Rt) were determined before and after bleeding in two groups of suckling chinchilla rabbits. One group was subjected to severe bleeding on the 12th, 15th, 18th and 21st day after birth and studied for 3 weeks, while the other was studied during the first 24 h after one severe bleeding on the 18th day. In the first group Hb and Hct fell to 2.7 g . dl-1 and 11.5%, respectively, on the 25th day. The fall was accompanied by a marked rise in Rt and decline in MCHC, reaching maximum and minimum on the 29th day, and a simultaneous, temporary decline in 2,3-DPG. In the other group the acute bleeding was accompanied by a marked fall in Hb and Hct, but no change in Rt and MCHC. 2,3-DPG was unchanged 8 h after the bleeding, but showed a rise during the following 16 h, definitely beyond the normal rise at this age. It is concluded that severe bleeding anaemia induces a rise in erythrocyte 2,3-DPG synthesis. However, the effect of the acute rise in 2,3-DPG is far from sufficient to maintain the O2 delivery capacity of the blood, and is completely offset by the influence of a subsequent change in the erythrocyte population towards younger cells with low 2,3-DPG.     

Erythrocyte 2,3-DPG,PO250% and available O2 during the early post-natal fall in hemoglobin in rabbits

Erythrocyte 2,3-DPG, PO₂50%, whole blood hemoglobin and available O₂, and fixed acid Bohr effect were studied during the first 10 days after birth in rapidly growing suckling rabbits. The post-natal fall in hemoglobin concentration was accompanied by a marked rise in erythrocyte 2,3-DPG and a gradual increase in PO₂50%. The rise in PO₂50% was sufficient to keep the available O₂ of the blood unchanged throughout the observation period. The observations show that a 2,3-DPG mediated rise in PO₂50% very effectively contributes to maintenance of adequate tissue oxygenation during the post-natal fall in hemoglobin. The rise in 2,3-DPG and PO₂50% may be due to the ordinary hypoxia-induced shift to the right of the hemoglobin O₂ dissociation curve, as observed under other circumstances when blood hemoglobin is rapidly reduced, but the very marked rise in 2,3-DPG and the very low Δ PO₂50%/Δ 2,3-DPG ratio suggest that the rise may as well be due to hypoxia independent, pre-programmed processes. The fixed acid Bohr effect was essentially the same in newborn and adult rabbits, and was uninfluenced by large variations in 2,3-DPG.     

Erythrocyte 2,3-diphosphoglycerate, PO2 50% and available O2 in rabbits with bleeding anaemia superimposed on the early post-natal fall in haemoglobin

Erythrocyte 2,3-diphosphoglycerate (2,3-DPG), PO2 50%, whole blood haemoglobin (Hb), haematocrit (Hct) and available O2 were determined in two matched groups of suckling rabbits from the 17th to the 34th day after birth. One group was subjected to repeated bleeding, amounting to 1.0-1.5% of the body weight, on day 17, 19, 22 and 25, while the other served as control. The bleeding group had markedly lower Hb and Hct than the control group, which showed the ordinary post-natal fall in Hb. There were, however, no differences between 2,3-DPG and PO2 50% in the two groups. The changes were essentially the same as observed previously in animals in which the post-natal anaemia was avoided by iron-treatment. Thus, these and previously reported data show that the post-natal rise in 2,3-DPG and PO2 50% within wide limits is uninfluenced by marked variations in Hb, even severe bleeding anaemia, and support the assumption that the post-natal rise in 2,3-DPG and PO2 50% is dominated by processes related to the growth and maturation of the animals.     

Erythropoiesis-stimulating factor(s), erythropoiesis and erythrocyte 2,3-diphosphoglycerate in young rabbits with marked post-natal fall in haemoglobin

The erythropoietic activity and erythrocyte 2,3-diphosphoglycerate (2,3-DPG) were studied during and after the nadir of the post-natal anaemia in normal, rapidly growing rabbits, from the 12th to the 35th day after birth. Whole blood haemoglobin (Hb) decreased from 9.3 g dl-1 on the 12th to 4.9 g dl-1 on the 25th day, while erythropoiesis-stimulating factor(s) (ESF) in plasma (determined by a cell culture assay) concomitantly rose from undetectable to high levels. In spite of marked rise in body weight, from 250 to 480 g, estimated haemoglobin mass (Hb mass) and reticulocyte mass production rate (Rt prod) remained essentially the same, about 1.8 g and 0.3 ml day-1. From the 25th to the 35th day, ESF decreased to a lower level, while Hb increased to 10.8 g dl-1 and Hb mass and Rt prod rose sharply, to 6.9 and 1.2 ml day-1. The 2,3-DPG rose markedly during the observation period, but showed a transient decline on the 29th day, simultaneously with the peak in reticulocyte counts (Rt) (24%) and release of young erythrocytes with low 2,3-DPG. The data indicate that the regions governing the erythropoietin production/release became increasingly sensitive to hypoxia during the observation period. The possibility also exists that the increase in ESF was due only in part to hypoxic stimulation. It could be related to the maturation of the animal in other ways, such as shift from extra-renal to renal erythropoietin production and the growth. The lack of response to increasing stimulation indicates that the erythropoiesis was restricted by the availability of iron and/or other factors necessary for erythrocyte and haemoglobin production.     

Thyroxine and red cell 2,3-diphosphoglycerate in the newborn period

Summary In 12 healthy newborn infants, red cell 2,3-diphosphoglycerate and plasma thyroxine levels were studied during the first 2 weeks of life. The data obtained indicate that thyroxine increases the 2,3-diphosphoglycerate concentration in the erythrocytes. Thus, thyroxine initiates via 2,3-diphosphoglycerate the accelerated decline of hemoglobin oxygen affinity taking place after birth, which facilates oxygen release from hemoglobin to the tissues.Supported by Deutsche Forschungsgemeinschaft, Sonderforschungsbereich 51 Medizinische Molekularbiologie und Biochemie.     

Effects of anaemia and stepwise-induced polycythaemia on maximal aerobic power in individuals with high and low haemoglobin concentrations

Increasing the haemoglobin concentration ([Hb]) improves the oxygen transport capacity but it also increases the viscosity of the blood. The influence of changes in [Hb] and viscosity on submaximal exercise capacity and maximal aerobic power was investigated in eight healthy males in varying states of training and with a normal resting [Hb] ([Hb]_r), ranging from 123 to 178 g]^-1. The subjects were venesected five times (450 ml per unit) and exercise tests were performed in the anaemic state. After 5–7 weeks, when [Hb] had returned to the ‘normal’ value, a stepwise re-transfusion of three to five units of blood was performed with exercise tests after each transfusion. The [Hb]_r was 137 ± 15 g l^-1 in the anaemic state (A) and 170 ± 16 g l^-1 after the last re-transfusion (LT). The V_o2max rose from 3.94 ± 0.35 in A to 4.68 ± 0.30 1 min^-1 after LT. Individual regression lines for [Hb] and V_o2max revealed a mean increase in V_o2max of 19 ± 6 ml min^-1 per g l^-1 change in [Hb]. This value did not differ between individuals with high and low normal [Hb]. Furthermore, in intra-individual comparisons the relationship between [Hb] and V_o2max in high and low individual [Hb] ranges was not found to be statistically different despite a 40% increase in the in vitro viscosity from the anaemic to the polycythaemic state. The average individual correlation (based on five to seven measurements) between [Hb] at rest and after exercise and V_o2max was r= 0.89 (P > 0.01) in the former case and r= 0.92 (P > 0.01) in the latter. The running velocity corresponding to a blood lactate concentration of 4 mM (V_Hla4.0) increased from 15.3 ± 2.3 in the control state to 15.6±2.3 km h¹ after the last transfusion (P > 0.01). A leftward shift of the blood lactate curve, expressed as a percentage of V_o2max, was found. In conclusion, the results obtained indicate a close relationship between V_o2max and [Hb] up to at least 170 g l^-1. Furthermore, both inter-and intra-individual comparisons suggest that the influence of viscosity as such on V_o2max does not differ at high and low [Hb] levels.