The role of hemoglobin oxygen affinity in oxygen transport at high altitude

Hemoglobin is involved in the regulation of O(2) transport in two ways: a long-term adjustment in red cell mass is mediated by erythropoietin (EPO), a response to renal oxgyenation. Short-term, rapid-response adjustments are mediated by ventilation, cardiac output, hemoglobin oxygen affinity (P50), barriers to O(2) diffusion, and the control of local microvascular tissue perfusion. The distribution of O(2) between dissolved (PO2) and hemoglobin-bound (saturation) is the familiar oxygen equilibrium curve, whose position is noted as P50. Human hemoglobin is not genetically adapted for function at high altitude. However, more specialized species native to high altitudes (guinea pig and bar-headed goose, for example) seem to have a lower P50 than their sea level counterparts, an adaptation that presumably promotes O(2) uptake from a hypoxic environment. Humans, native to very high altitude either in the Andes or Himalayan mountains, also can increase O(2) affinity, not because of a fundamental difference in hemoglobin structure or function, but because of extreme hyperventilation and alkalosis.     

Sex differences in the oxygen affinity of hemoglobin

Summary The oxygen dissociation curves of 50 healthy young nonsmokers 25 women and 25 men, were investigated. The following parameters were deter-mined: hemoglobin concentration, microhematocrit, red cell count, mean corpuscular hemoglobin concentration, capillary blood pH,P ₅₀ value, and the concentration of red cell 2,3-diphosphoglycerate. P ₅₀ values are significantly higher in the female group (28.3 mm Hg±0.4 S.E.M.) than in the male group (26.3 mm Hg±0.4 S.E.M.), indicating a lower oxygen affinity of hemoglobin in females.There is no significant difference between the DPG values. No significant negative correlation exists between the Hb concentration and theP ₅₀ values.with the technical assistance of Monika Humpeler and Edith Gasser     

Hemoglobin Jamaica plain--a sickling hemoglobin with reduced oxygen affinity

A baby girl presented with symptomatic sickle cell disease exacerbated by mild hypoxemia, despite a newborn-screening diagnosis of sickle cell trait. DNA sequencing of the beta globin gene revealed that her maternal beta globin allele was normal. Her paternal allele had not only the expected sickle-trait mutation, betaGlu6Val, but also a second, charge-neutral mutation, betaLeu68Phe. Analysis of the patient's hemoglobin revealed that the double-mutant protein, which we called "hemoglobin Jamaica Plain," had severely reduced oxygen affinity. Structural modeling suggested destabilization of the oxy conformation as a molecular mechanism for sickling in a heterozygote at an ambient partial pressure of oxygen.     

Relationship between hemoglobin affinity for oxygen and lipid peroxidation in fever

Hemoglobin affinity for oxygen (P₅₀ parameter) and the content of malonic dialdehyde (MDA), Schiff's bases, and diene conjugates in the plasma and red cell mass were examined in mixed venous blood of rabbits with pyrogenal fever. Correlation regression analysis of the tested parameters showed that reduction of the actual affinity of hemoglobin for oxygen is conducive to activation of free-radical processes. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 118, N ^o 7, pp. 27–30, July, 1994 Presented by K. V. Sudakov, Member of the Russian Academy of Medical Sciences     

Effect of an allosteric modifier of hemoglobin, RSR-4, on oxygen affinity and oxygen saturation of hemoglobin in rabbits

Theoretically, if the arterial partial oxygen pressure (PaO2) does not change, a right shift in the oxygen equilibrium curve (OEC) of hemoglobin should reduce arterial oxygen saturation. In this study we investigate whether a right shift in the OEC of hemoglobin decreases transcutaneous oxygen saturation (Tc-SO2) following the administration of an allosteric effector, 2-[4-(((3, 5-dichloroanilino)-carbonyl) methyl) phenoxy]-2-methylpropionic acid (RSR-4). The effect of RSR-4 on hemoglobin oxygen affinity was studied in four New Zealand white male rabbits. Following intraperitoneal administration of RSR-4, Tc-SO2 decreased in a dose-dependent manner. P50 (partial oxygen pressure at 50% hemoglobin oxygen saturation) in whole blood increased as the concentration of RSR-4 increased. Tc-SO2 decreased as whole-blood affinity (1/P50) decreased. There was no positive correlation between Tc-SO2 and PaO2. We concluded that a decrease in hemoglobin oxygen affinity following RSR-4 administration reduced arterial oxygen saturation. This decrease in the presence of an allosteric effector such as RSR-4 in vivo can be detected and monitored as a reduction in Tc-SO2.     

Diurnal rhythmic fluctuations of the oxygen affinity of hemoglobin in premature infants

Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 116, N ^o 10, pp. 425–428, October, 1993     

Optimum control of oxygen affinity of hemoglobin as an oxygen carrier solution for an artificial gill

An artificial gill was developed using a concentrated hemoglobin solution as an oxygen carrier solution, with the oxygen affinity controlled by temperature. Oxygen affinity of the concentrated hemoglobin solution was optimized for the artificial gill by adding inositol hexaphosphate as an allosteric effector and varying the pH and temperature. The oxyhemoglobin dissociation curve shifted to the right with increased ratios of inositol hexaphosphate to hemoglobin, decreased pH values, and higher temperatures. The optimum ratio of inositol hexaphosphate to hemoglobin was 5 : 1. Because lower pH promotes proton oxidation of hemoglobin, the optimum pH was 6.9. The oxyhemoglobin dissociation curve shifted to the right with higher temperatures. The amount of the shift in relation to temperature change was higher at higher temperatures. The oxygen transfer rate was markedly increased by changing the temperature of the oxygen carrier solution. The overall mass transfer coefficient decreased at higher oxygen partial pressures due to the gentle oxyhemoglobin dissociation curve. The flow rate of the oxygen carrier solution and heat transfer rate for heating of the oxygen carrier solution were markedly decreased by setting the range of temperature changes from 293 K to 310 K. The flow rate of the oxygen carrier solution required to supply 300 ml (STP)/min of oxygen was 21.7 l/min, and the heat transfer rate was 1165 kJ/min. Received: October 30, 2000 / Accepted: January 10, 2001     

Diminution of the temperature effect on the oxygen affinity of hemoglobin after prolonged hypothermia

The influence of temperature on the oxygen affinity of hemoglobin, expressed as half saturation tension, P₅₀, was investigated in male Sprague Dawley rats, which had been exposed to a cold environment for about 12 h. P₅₀-values were determined by equilibrating blood samples to a knownP _{O 2} at different temperatures. The well known increase in oxygen affinity at low temperatures was observed, but after a longer hypothermic period this effect was diminished. This reduction of the temperature effect is manifested in a change of the ratio log P₅₀/T from 0.022 in control experiments to 0.0115 in hypothermia. In cold adapted rats such an effect means a better oxygen supply to tissue at low body temperatures than in control animals. These changes in oxygen delivery after cold acclimatisation may partially be interpreted as the result of the decreased intraerythrocytic pH and elevated concentration of ATP found in the present study.Part of this work was presented at the 50th Meeting of the German Physiological Society in Göttinge, 1978 [13] and at the 16th Centraleuropean Anaesthesia Congress in Innsbruck, 1979     

Role of hemoglobin affinity for oxygen in the activation of lipid peroxidation during fever

Major parameters of oxygen transport and lipid peroxidation are measured in the blood of rabbits with fever, and it is found that hemoglobin affinity for oxygen is decreased while free-radical processes are activated in this state. The data are subjected to multiple correlation analysis and the matrix of paired correlation coefficients obtained for the measured parameters is presented. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 121, N ^o , pp. 44–47, January, 1996 Presented by K. V. Sudakov, Member of the Russian Academy of Medical Sciences     

Role of ionic transport in regulation of hemoglobin affinity for oxygen in diabetes mellitus

The rate of Na⁺/H⁺ exchange is increased by 24%, activities of Ca-dependent K+ channels is increased by 13%, and activity of erythrocyte Ca²⁺-ATPase decreased by 17% in patients with diabetes mellitus concomitant with essential hypertension in comparison with patients with essential hypertension without disorders of carbohydrate metabolism. Changes in activity of Na⁺/H⁺ exchange, Ca-dependent K⁺ channels, and erythrocyte Ca²⁺-ATPase and increased oxygen affinity of hemoglobin are due to increased glucose concentration in the plasma and are leveled by olifen.     

Hemoglobin-based artificial blood: new polymeric derivatives of hemoglobin with low oxygen affinity.

To make stroma-free hemoglobin (SFHb) capable of carrying oxygen satisfactorily in vivo it is necessary both to improve its intravascular persistence and to reduce its affinity for oxygen. The method used up to now has consisted of chemical modification of SFHb to lower its oxygen affinity (fixation of permanent effector inside the phosphate binding site or intramolecular cross-linking of the deoxy form of SFHb), then polymerization or substitution with polymers. We have designed new functionalized polymers (from dextran and polyoxyethylene), capable of mimicking the effect of the natural intraerythrocyte effector, 2,3-disphosphoglycerate, i.e. of decreasing its affinity for oxygen, and we have linked these polymers chemically to oxyHb. All the resulting conjugates have lower oxygen affinity than SFHb and, when injected into rats, do not lead to hemoglobinuria. Preliminary in vivo tests also showed that these conjugates possess no acute toxicity. Further experiments with rats are now under way (60% and 80% hemorrhagic shocks) with the aim of evaluating whether these new products can be regarded as potential candidates for blood substitution.