Increased blood oxygen affinity during digestion in the snakePython molurus

2002 ◽  
Vol 205 (21) ◽  
pp. 3327-3334 ◽  
Author(s):  
Johannes Overgaard ◽  
Tobias Wang

SUMMARYMany snakes exhibit large increases in metabolic rate during digestion that place extensive demands on efficient oxygen transport. In the present study,we describe blood oxygen affinity following three weeks of fasting and 48 h after feeding in the Burmese python (Python molurus). We also report simultaneous measurements of arterial blood gases and haematological parameters. Arterial blood was obtained from chronically implanted catheters,and blood oxygen-dissociation curves were constructed from oxygencontent measurements at known oxygen partial pressure(PO2) values at 2% and 5% CO2. Arterial pH remained constant at approximately 7.6 after feeding, but digestion was associated with an approximately 6 mmol l-1 increase in [HCO3-], while CO2 partial pressure(PCO2) increased from 2.21±0.13 kPa in fasted animals to 2.89±0.17 kPa at 48 h after feeding. Blood oxygen affinity in vivo was predicted on the basis of pH in vivoand the blood oxygen-dissociation curves obtained in vitro. The blood oxygen affinity in vivo increased during digestion, with P50 values decreasing from 4.58±0.11 kPa to 3.53±0.24 kPa. This increase was associated with a significant decrease in the red blood cell [NTP]/[Hb4] ratio (relationship between the concentrations of organic phosphates and total haemoglobin) and a significant decrease in mean cellular haemoglobin content, which is indicative of swelling of the red blood cells. Our data for blood oxygen affinity and arterial oxygen levels, together with previously published values of oxygen uptake and blood flows, allow for a quantitative evaluation of oxygen transport during digestion. This analysis shows that a large part of the increased metabolism during digestion is supported by an increased venous extraction, while arterial PO2(PaO2) and haemoglobin saturation do not vary with digestive status. Thus, we predict that venous PO2 (PvO2) is reduced from a fasting value of 5.2 kPa to 1.6 kPa during digestion.

1980 ◽  
Vol 238 (1) ◽  
pp. H73-H79 ◽  
Author(s):  
P. A. Mueggler ◽  
G. Jones ◽  
J. S. Peterson ◽  
J. M. Bissonnette ◽  
R. D. Koler ◽  
...  

A rightward shift in the blood oxygen dissociation curve occurs during the 1st mo of canine life. A detailed peptide analysis indicated that dogs do not have a separate fetal hemoglobin. Other erythrocyte components such as ATP, K+, Na+, and H+ were excluded as significant mediators of the postnatal oxygen affinity change. Erythrocyte 2,3-DPG levels essentially zero in fetal dogs, increased rapidly during the 1st mo of canine life. There was a significant correlation between this postnatal 2,3-DPG increase and the postnatal decrease in blood oxygen affinity. Dialyzed hemolysates of fetal or adult canine blood have the same intrinsic oxygen affinity and the same response to normal adult levels of 2,3-DPG. Furthermore, the magnitude and direction of this 2,3-DPG-induced decrease in oxygen affinity in vitro are comparable to the in vivo postnatal change in oxygen affinity.


1984 ◽  
Vol 57 (1) ◽  
pp. 14-20 ◽  
Author(s):  
A. Zwart ◽  
G. Kwant ◽  
B. Oeseburg ◽  
W. G. Zijlstra

Oxygen dissociation curves (ODC) were recorded in the presence of carboxyhemoglobin fractions (FHbCO) up to 60%. The gradual shift to the left of the ODC at increasing amounts of HbCO was reflected in a gradual fall in the half-saturation pressure of the remaining Hb and was accompanied by a gradual change in the shape of the ODC to a hyperbolic one. The H+ factor (delta log PO2/delta pH) was determined over the entire oxygen saturation (SO2) range at three different FHbCO levels (14, 30, and 52%). At FHbCO = 14 and 30% and for the SO2 range 20–90%, the H+ factor vs. SO2 curve was not significantly different from that in the absence of HbCO. At FHbCO = 52%, however, the value found for the H+ factor (-0.55) was appreciably more negative than in the case of blood containing less than 1% HbCO (-0.44), and there was no dependence on SO2. Comparison of measured and calculated ODCs at varying HbCO fractions showed, for FHbCO less than or equal to 50%, that measured and calculated ODCs coincide over the greater part of the SO2 range. For FHbCO greater than 50%, the measured ODC was situated to the left of the calculated one over the entire SO2 range. We conclude that the heme-heme interaction for CO is appreciably larger than for O2 only for FHbCO greater than 50%, whereas for FHbCO less than 50% there is virtually no difference.


1976 ◽  
Vol 230 (6) ◽  
pp. 1751-1754 ◽  
Author(s):  
TB Allison ◽  
GM Pieper ◽  
FC Clayton ◽  
RS Eliot

The effects of increased blood-oxygen affinity, due to carbamylation of hemoglobin in vivo, on aerobic metabolism in the heart were studied in rats. Adult male rats were injected intraperitoneally 3 times weekly for 10 wk with sodium cyanate (60 mg/kg). Significant derangement of blood-oxygen interaction was observed. Oxygen-dissociation curves were left shifted by 13 mmHg (35.1-21.8), and the overall deoxygenation rate (k) was reduced 41% (6.142-3.624; s(-1)); P is less than 0.001 for each parameter. Heart ATP and PCr levels were reduced (ATP: 19.4-16.7; PCr: 15.0-11.0, mum/g dry wt; P is less than 0.001 for each). In addition, glycogen levels fell (161.4-112.9, mum C6/g dry wt; P is less than 0.001). Myocardial lactate levels increased 54% (2.6-4.0, mum/g dry wt; P is less than 0.01) in the cyanate-treated group. These findings strongly suggest a hypoxia-induced activation of glycolysis as a consequence of altered oxidative metabolism in rats treated with sodium cyanate.


Blood ◽  
1972 ◽  
Vol 39 (3) ◽  
pp. 398-406 ◽  
Author(s):  
Frank G. de Furia ◽  
Denis R. Miller

Abstract Oxygen affinity studies in a splenectomized patient with sporadically occurring Hb Köln disease revealed high whole blood oxygen affinity (P50 O2 17.6 mm Hg) with increased 2, 3-diphosphoglycerate (DPG), low ATP, and normal RBC ΔpH. Isolated electrophoretically slow migrating Hb Köln had a high oxygen affinity, decreased Hill’s number, and normal DPG reactivity. Functional evidence for hybrid tetramers with normal mobility is presented. Partial deoxygenation may play a role in the denaturation of the Hb Köln molecule and thus account for a higher oxygen affinity (low P50 O2), measured by the mixing technique, than the actual values for P50 that exist in vivo. Increased oxygen affinity and decreased P50 O2 would result in increased erythropoiesis and account for a well-compensated hemolytic process in this patient with a normal red cell mass and normal values of hemoglobin.


Blood ◽  
2021 ◽  
Author(s):  
Eric R Henry ◽  
Belhu Metaferia ◽  
Quan Li ◽  
Julia Harper ◽  
Robert B Best ◽  
...  

The issue of treating sickle cell disease with drugs that increase hemoglobin oxygen affinity has come to the fore with the FDA approval in 2019 of voxelotor, the only anti-sickling drug approved since hydroxyurea in 1998. Voxelotor reduces sickling by increasing the concentration of the non-polymerizing, high oxygen affinity R (oxy) conformation of HbS. Treatment of sickle cell patients with voxelotor increases Hb levels and decreases indicators of hemolysis, but with no indication as yet that it reduces the frequency of pain episodes. Here we use the allosteric model of Monod, Wyman, and Changeux to simulate whole blood oxygen dissociation curves and red cell sickling in the absence and presence of voxelotor under the in vivo conditions of rapid oxygen pressure decreases. Our modeling agrees with experiments using a new robust assay, which shows the very large, expected decrease in sickling from the drug. The modeling indicates, however, that the increase in oxygen delivery from reduced sickling is largely offset by the increase in oxygen affinity. The net result is that the drug increases overall oxygen delivery only at the very lowest oxygen pressures. Reduction of sickling does, however, mitigate against red cell damage and explains the observed decrease in hemolysis. More importantly, our modeling of in vivo oxygen dissociation, sickling, and oxygen delivery suggests that drugs that increase fetal hemoglobin or decrease MCHC, should be more therapeutically effective than drugs that increase oxygen affinity.


1984 ◽  
Vol 109 (1) ◽  
pp. 265-279
Author(s):  
VILHELM TETENS ◽  
RUFUS M. G. WELLS ◽  
ARTHUR L. DEVRIES

1. The effects of thermal acclimation on whole blood oxygen affinity were examined in the antarctic fish Pagothenia borchgrevinki. 2. 4.5°C-acclimated fish had a P50 value of 26.7 mmHg at pH 8.1, compared to 20.7 mmHg for −1.5°C-acclimated fish. The apparent heat of oxygenation, ΔH = −26.7 kJ mol−1, is comparable to values for temperate species. 3. Warm-acclimation was followed by an increased ATP: Hb4 molar ratio, resulting in an augmentation of the thermal effect on oxy-haemoglobin affinity. This may be considered adaptive in a constantly well oxygenated environment, where oxygen loading at the gills is secured. Unloading to the tissues is thereby enhanced, supporting an elevated rate of aerobic metabolism at higher temperatures. 4. In vivo blood pH was high, between 8.10 and 8.25 at −1.5°C. Astrup titration revealed arterial CO2 tensions of less than 0.8 mmHg, indicating relative hyperventilation and low oxygen extraction efficiency in antarctic fish. 5. Blood oxygen affinities of four antarctic nototheniid species were low (P50 between 11.9 and 20.7 mmHg at pH 8.1 and --1.5°C) in comparison with the temperate species Notothenia angustata (P50 = 10.8 mmHg). The zoarcid Rhigophila dearborni had a high blood oxygen affinity (P50 = 4.3 mmHg). Blood oxygen-binding properties are discussed in relation to the polar environment, mode of life, and the concept of cold adaptation.


1992 ◽  
Vol 262 (2) ◽  
pp. H517-H522 ◽  
Author(s):  
J. C. Stein ◽  
M. L. Ellsworth

The impact of an increased hemoglobin oxygen affinity (decreased P50) on oxygen transport was evaluated in capillaries of the retractor muscle under nonhypoxic (FIo2 = 0.30 and 0.21) and hypoxic (FIo2 = 0.10) conditions in hamsters with normal oxygen affinity [control; P50 = 26.1 +/- 1.0 (SD) mmHg, n = 12] and in hamsters with an increased oxygen affinity [treated; P50 = 16.2 +/- 1.6 (SD) mmHg, n = 7] induced by chronic short-term administration of sodium cyanate. Using in vivo video microscopy and computer-aided image analysis, we determined oxygen saturation (SO2) and associated hemodynamic parameters in both arteriolar (n = 30 control, 18 treated) and venular (n = 25 control, 17 treated) capillaries. In response to hypoxia, systemic arterial PO2 decreased to 29.6 +/- 6.0 (SD) mmHg in control animals and 24.7 +/- 3.8 (SD) mmHg in treated animals associated with abrupt decreases in systemic arterial blood pressure and increases in respiratory rate. The decrease in SO2 across the capillary network during nonhypoxic ventilation was 13.3% SO2 for control animals and 11.0% SO2 for treated animals. During hypoxic ventilation, the decrease in SO2 was 9.1% SO2 in control animals and 8.7% SO2 in treated animals. Hemodynamic parameters were not significantly different in the two groups during hypoxia. Estimated end-capillary PO2 was significantly lower in the treated animals. These data indicate that an increased oxygen affinity does not provide an obvious advantage for oxygen transport during hypoxia at the level of the capillary network in resting striated muscle; however, such an advantage might become apparent in the presence of an increased metabolic rate or a more severe hypoxic challenge.


2000 ◽  
Vol 203 (20) ◽  
pp. 3117-3124 ◽  
Author(s):  
M. Busk ◽  
J. Overgaard ◽  
J.W. Hicks ◽  
A.F. Bennett ◽  
T. Wang

Reptiles habitually ingest large meals at infrequent intervals, leading to changes in acid-base status as the net secretion of acid to the stomach causes a metabolic alkalosis (the alkaline tide). In chronically cannulated and undisturbed amphibians and reptiles, the pH changes in arterial blood are, nevertheless, reduced by a concomitant respiratory acidosis (increased P(CO2) caused by a relative hypoventilation). Alligators (Alligator mississippiensis) have been reported to exhibit exceptionally large increases in plasma [HCO3(−)] following feeding, but these studies were based on blood samples obtained by cardiac puncture, so stress and disturbance may have affected the blood gas levels. Furthermore, crocodilian haemoglobin is characterised by a unique binding of HCO3(−) that act to reduce blood oxygen-affinity, and it has been proposed that this feature safeguards oxygen offloading by counteracting pH effects on blood oxygen-affinity. Therefore, to study acid-base regulation and the interaction between the alkaline tide and oxygen transport in more detail, we describe the arterial blood gas composition of chronically cannulated and undisturbed alligators before and after voluntary feeding (meal size 7.5+/−1% of body mass). Digestion was associated with an approximately fourfold increase in metabolic rate (from 0.63+/−0.04 to 2.32+/−0.24 ml O(2) min(−1)kg(−1)) and was accompanied by a small increase in the respiratory gas exchange ratio. The arterial P(O2) of fasting alligators was 60.3+/−6.8 mmHg (1 mmHg = 0.133 kPa) and reached a maximum of 81.3+/−2.7 mmHg at 96 h following feeding; there was only a small increase in lactate levels, so the increased metabolic rate seems to be entirely aerobic. Plasma [HCO3(−)] increased from 24.4+/−1.1 to 36.9+/−1.7 mmol l(−1) (at 24 h), but since arterial P(CO2) increased from 29.0+/−1.1 to 36.8+/−1.3 mmHg, arterial pH remained virtually unaffected (changing from 7.51+/−0.01 to 7.58+/−0.01 at 24 h). The changes in plasma [HCO3(−)] were mirrored by equimolar reductions in plasma [Cl(−)]. The in vitro blood oxygen-affinity was reduced during the post-prandial period, whereas the estimated in vivo blood oxygen-affinity remained virtually constant. This supports the view that the specific HCO3(−) effect prevents an increased blood oxygen-affinity during digestion in alligators.


1991 ◽  
Vol 260 (4) ◽  
pp. R798-R803
Author(s):  
M. Riera ◽  
J. F. Fuster ◽  
L. Palacios

The effects of two different degrees of experimentally induced anemia and the consequent high percentage of circulating immature erythrocytes on oxygen affinity (pH 7.5 and 41 degrees C), erythrocyte organic phosphates, and Hb fractions have been studied in quail. Blood reticulocytes reached percentages of 24 and 69-87% in the first and second experiments, respectively. Variations in the phosphate levels found during the anemic process were related to the amount of circulating reticulocytes. The erythrocyte [ATP] (brackets indicate concentration) and [ATP]/[Hb] molar ratio increased with the release of reticulocytes and returned to control levels as they matured. The erythrocyte [inositol pentakisphosphate (InsP5)] decreased significantly when circulating reticulocytes showed their highest values, whereas there was hardly any effect on the [InsP5]/[Hb] molar ratio, which changed only slightly. Hb-O2 affinity also exhibited no statistical changes associated with acute anemia. These latter findings indicate that InsP5, at physiological concentrations, is the primary modulator of quail Hb function; the observed rise in [ATP] has no additional influence on Hb-O2 affinity. It is suggested that InsP5 tends to maintain the blood oxygen affinity in both mature erythrocytes and reticulocytes. The main compensatory response at blood level is a rapid bulk reticulocyte release from medulla.


2020 ◽  
Vol 128 (6) ◽  
pp. 1467-1476
Author(s):  
Glenn M. Stewart ◽  
Steven Chase ◽  
Troy J. Cross ◽  
Courtney M. Wheatley-Guy ◽  
Michael J. Joyner ◽  
...  

In humans, a novel allosteric hemoglobin-oxygen affinity modulator was administered to comprehensively examine the cardiopulmonary consequences of stabilizing a portion of the available hemoglobin in a high-oxygen affinity state during submaximal exercise in normoxia and hypoxia. Oral administration of voxelotor enhanced arterial oxygen saturation during submaximal exercise without altering oxygen consumption and central hemodynamics; however, the partial pressure of arterial carbon dioxide was reduced and the partial pressure of arterial oxygen was increased implying that hyperventilation also contributed to the increase in oxygen saturation. The preservation of arterial oxygen saturation and content was particularly evident during hypoxic submaximal exercise, when arterial desaturation typically occurs, but this did not influence arterial-venous oxygen difference.


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