The in-vivo oxyhaemoglobin dissociation curve at sea level and high altitude

Animals native to hypoxic environments have adapted by increasing their haemoglobin oxygen affinity, but in-vitro studies of the oxyhaemoglobin dissociation curve (ODC) in humans show no changes in affinity under physiological conditions at altitudes up to 4000 m. We conducted the first in-vivo measurement of the ODC; inducing progressive isocapnic hypoxia in lowlanders at sea level, acutely acclimatized lowlanders at 3600 m, and native Andeans at that altitude. ODC curves were determined by administering isocapnic steps of increasing hypoxia, and measuring blood oxygen partial pressure and saturation. The ODC data were fitted using the Hill equation and extrapolated to predict the oxygen partial pressure at which haemoglobin was 50% saturated (P₅₀). In contrast to findings from in-vitro studies, we found a pH-related reduction in P₅₀ in subjects at altitude, compared to sea-level subjects. We conclude that a pH-mediated increase in haemoglobin oxygen affinity in-vivo may be part of the acclimatization process in humans at altitude.     

Noninvasive measures of blood volume and oxygen saturation of human Achilles tendon by red laser lights

Aim: Spectroscopic measurement using near‐infrared spectroscopy and red laser lights was performed to investigate the blood volume (total haemoglobin; THb) and oxygen saturation (oxygenated haemoglobin saturation; StO₂) of the human Achilles tendon during single and repetitive isometric contractions. Methods: Twelve men performed isometric plantar flexion exercises at intensities of 10% (3 min), 30% (2 min), 50% (1 min) and 70% (30 s) of the maximum voluntary contraction (MVC). In addition, they performed 50 repetitions at 70% of the MVC with 5‐s contractions and a 5‐s gap between repetitions for 10 min. The probes were positioned on the Achilles tendon and medial gastrocnemius muscle. Results: THb and StO₂ of the Achilles tendon decreased during ‘single’ contraction at all force levels. On the other hand, after the end of the repetitive exercises, THb and StO₂ of the Achilles tendon increased gradually, and remained at this level until the end of the recovery period. Conclusion: The blood volume and oxygen saturation within the human Achilles tendon increased after the ‘repetitive’ muscle contractions, while they decreased after the ‘single’ contraction. Furthermore, the increases in blood volume and oxygen saturation within the tendon after repetitive contractions may be related to tendon repair after exercises involving mechanical loading of the tendon.     

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.     

Hemoglobin oxygen affinity in patients suffering from arterial occlusive disease of the legs

Summary Parameters characterizing the hemoglobin oxygen affinity were determined in blood of 12 male patients suffering from arterial occlusive disease (AOD) of the legs and compared with data obtained earlier from healthy human subjects (controls). Due to a COHb content of 4.8%±2.2% in the cigarette-smoking AOD patients, the standard oxygen dissociation curve (ODC) was left-shifted, the half-saturation pressure (P₅₀) amounted to 24.8±1.7 mmHg (3.30±0.23 kPa), although the 2,3-diphosphoglycerate concentration was increased to 15.3±1.7 µmol/g Hb. Correcting the effects of elevated COHb shifts the P₅₀ to 26.3 mmHg (3.5 kPa) and increases the steepness of the ODC (Hill's n) from 2.79±0.27 to about 2.99, which is significantly different from controls. The Bohr coefficients after acidification of blood with lactic acid (BC_Lac) show high values at low oxygen saturations of hemoglobin (–0.50±0.04 in AOD patients, –0.32±0.04 in controls;P<0.05 at 10% S_O2). The cause of the alterations in hemoglobin oxygen affinity may be a reduced mean erythrocyte age, but also the influence of unknown factors generated, e.g., from anaerobic muscle metabolism in AOD.Abbreviations AOD Arterial occlusive disease of the legs - BC Bohr coefficient - BC_CO2 Bohr coefficient after acidification of blood with CO₂ - BC_Lac Bohr coefficient after acidification of blood with lactic acid - DPG 2,3-Diphosphoglycerate - ODC Oxygen dissociation curve - P₅₀ Oxygen pressure when hemoglobin is half-saturated     

A dual control system for assisting respiration

A dual control system for assisting respiration was developed. The following features were included: (i) ventilation is controlled by the metabolic rate from continuously measured CO₂ output, (ii) physiologic dead space approximated as a linear function of tidal volume is used to estimate alveolar ventilation, and (iii) oxygen concentration in the inspired gas is regulated by the arterial oxygen saturation continuously measured with an ear oximeter. The ventilator was used on dogs with an inspired gas mixture of 85% N₂ and 15% O₂. Arterial P_co2 was maintained between 36 and 39 mmHg for a duration exceeding 60 minutes. Although an oscillatory variation was seen in the arterial P_o2 due to the adoption of an on-off control mode to regulate the O₂ fraction in the inspired gas, it remained between 80 and 136 mmHg. The dual control system of assisting respiration is capable of maintaining both the arterial P_co2 and P_o2 within normal levels at any level of metabolic rate and any respiratory frequency.     

Die Nierenmarkhypoxie: Ein Schlüssel zum Verständnis des akuten Nierenversagens?

Summary The ability to produce a concentrated urine is imposed by a uniquely low ambient oxygen pressure in the renal medulla due to shunt diffusion within the vascular bundles. As the thick ascending limb of Henle's loop (TAL-segment) is able to glycolyse anaerobically, a phase of oxygen deficiency may be bridgespanned. It allows an exceptionally high oxygen extraction of 80% in this area. If oxygen capacity is reduced systematically, which can be effected in the isolated kidney model by using cell free perfusate, a typical pattern of lesions occur in TAL-segments. Segments near vascular bundles remain intact, as they take advantage from a radial oxygen diffusion originating from vascular bundles. The extent of lesions is increasing directed to the inner medulla due to the reduction of oxygen pressure, whereas lesions are not present in the inner medulla itself. Cells of TAL-segments are swelling during oxygen deficiency, when transport work surpasses the available energy necessary due to the luminal fluid inflow. Lesions could be prevented, when oxygen capacity was enhanced by adding erythrocytes or when transport was blocked by furosemide. Swollen cells in TAL-segments however are able to aggravate medullary hypoxia by an outflow block in vivo.Secondly, it can be demonstrated, that oxygen shunt diffusion is not only present in renal medulla but also within renal cortex especially as a preglomerular diffusion shunt for blood gases. Thus PCO₂ has been measured to be 65 mmHg in the outermost cortical zone and thereby some 20 mmHg higher than renal venous blood. Our own measurements of the PO₂ at superficial glomeruli in vivo using MWF-rats demonstrate values as low as 42–46 mmHg at average and a simultaneously measured arterial PO₂ of 90 mmHg in systemic blood. This represents a markedly higher desaturation of hemoglobin than found in renal venous blood. This unexpected high preglomerular shuntdiffusion is likely localized within interlobular vessels, where thinwalled arteries and veins exhibiting the wall structure of capillaries are generally in close contact. Following this concept, PO₂ of the superficial cortical zone is low and the PO₂ of the juxtamedullary cortical zone is not far from arterial PO₂. Plasmaskimming may modify O₂-pressure as well as O₂-capacity within the different cortical zones. These results may explain, why proximal tubules within the renal cortex — which exhibit a low enzymatic activity to glycolyse anaerobically compared to TAL-segments — develop lesions very rapidly under ischemic or hypoxic conditions or when the demand of energy for transport work cannot be produced aerobically. This becomes evident especially within areas of oxygen deficiency at the outer stripe of outer medulla, where predominantly P₃-segments in the interbundle area are involved however much less TAL-segments. This may also explain, that the production of erythropoietin is localized within the renal cortex and outer stripe of outer medulla, as oxygen deficiency can be measured effectively in this area. The common error, that oxygen supply of the kidney is abundant, must be revised: it is at the brink of oxygen deficiency in the case of renal medulla and at shortage also for renal cortex.     

Effect of the substituted benzaldehyde 12C79 on Cl–-dependent K+ influx in human red blood cells

 Ouabain- and bumetanide-resistant K⁺ influx, and haemoglobin (Hb) O₂ saturation, were measured in HbA red cells over a range of oxygen tensions (PO₂ values) in the presence and absence of 12C79 (5 mM), a substituted benzaldehyde which increases the O₂ affinity of Hb. PO₂ values for half-maximal O₂ saturation declined from 29±2 mmHg (mean ±SEM, n=3) in control cells to 7±1 mmHg with 12C79. In control cells, Cl^–-dependent K⁺ influx (indicative of KCl cotransport activity) was fully O₂ dependent, i.e. inactive at low PO₂ values. By contrast, in the presence of 12C79, KCl cotransport was largely resistant to inactivation at low PO₂ values. Substantial cotransport activity was still present (>60% of that at high PO₂ values) in N₂, although O₂ saturation was low (about 10%). In all cases, Cl^–-independent K⁺ influxes were low [<0.25 mmol (l cells h)^–1] and unaffected by PO₂ or 12C79. The significance of these results is discussed. Received: 10 August 1998 / Received after revision: 26 October 1998 / Accepted: 27 October 1998     

Erythropoietic adaptations to endurance training

Summary Erythropoietic adaptations involving the oxygen dissociation curve (ODC) and erythropoietin production have been implicated in the etiology of reduced blood haemoglobin concentrations in sportspersons (known as sports anaemia). A significant increase in the half-saturation pressure indicating a right-shift in the ODC was measured in 34 male [25.8–27.4 mmHg (3.44–3.65 kPa)] and 16 female (25.8–27.7 mmHg (3.44–3.69 kPa)] trained distance runners (P<0.01 for both genders) after completing a standard 42-km marathon. Erythrocyte 2,3-diphosphoglycerate concentrations measured concurrently were unaltered by exercise, although consistently higher in the female compared to the male athletes (P<0.05). The serum erythropoietin (EPO) concentrations of 15 male triathletes (26.3 U · ml^–1) were significantly lower than those of 45 male distance runners (31.6 U · ml^–1 ;P<0.05). However, the mean serum EPO concentrations of male and female athletes engaged in a variety of sports were not different from those of sedentary control subjects of both sexes (26.5–35.3 U · ml^–1). Furthermore, the serum EPO concentrations were unaltered after prolonged strenuous exercise in 20 male marathon runners. These data suggest that the haematological status of these endurance athletes is in fact normal and that the observed shift in the ODC, while providing a physiological advantage during exercise, has no measurable effect on the erythropoietic drive.     

Comparison of central venous saturation by standard ABG machine versus co-oximeter: Is 18 carat as good as the 24 carat gold standard?

Aims:

Aggressive therapy aimed at desired end-points of Early Goal Directed Therapy (EGDT) is the cornerstone of septic shock management. A key endpoint that improves outcomes is achieving central venous saturation (ScvO₂) >70%. The gold standard to measure ScvO₂ is by a co-oximeter (co-ox).

Settings and Design:

This prospective, observational study from a multidisciplinary pediatric intensive care unit (PICU) was conducted to assess the validity of ScvO₂ levels by standard ABG (stand ABG) machine in comparison with co-ox in conditions that shifted the oxygen dissociation curve (ODC) to the right or left in sick children and controls.

Materials and Methods:

Data from paired samples was tested for correlation coefficient for pH, paCO₂, paO₂, and ScvO₂. Tests for correlation (Pearson''s coefficient) and agreement (Bland–Altman analysis) were performed on ScvO₂ values obtained in various subgroups. Sensitivity and specificity for ScvO₂ values determined by standard ABG machine versus co-ox were calculated in reference to EGDT endpoints.

Results:

A total of 141 paired samples were collected from 82 children. Despite a statistically significant difference in the pH and ScvO₂, there was good linear correlation between these parameters. Limits of agreement between ScvO₂ measured by standard ABG machine and co-ox by Bland–Altman gave 2.3% bias with 95% CI of -24.2% to 19.5%. Sensitivity and specificity of standard ABG machine in detecting low ScvO₂ in shock was 84.21% and 93.18% respectively, while it was false positive in 4 samples.

Conclusions:

The less expensive standard ABG machine showed satisfactory correlation with gold standard co-ox over a range of patient conditions; however, the wide range for agreement was of concern and it performed particularly poorly in anemic patients.     

Near‐infrared spectroscopy determined brain and muscle oxygenation during exercise with normal and resistive breathing

To elevate effects of carbon dioxide (CO₂) retention by way of an increased respiratory load during submaximal exercise (150 W), the concentration changes of oxy‐ (ΔHbO₂) and deoxy‐haemoglobin (ΔHb) of active muscles and the brain were determined by near‐infrared spectroscopy (NIRS) in eight healthy males. During exercise, pulmonary ventilation increased to 33 (28–40) L min^–1 (median with range) with no effect of a moderate breathing resistance (reduction of the pneumotach diameter from 30 to 14 and 10 mm). The end‐tidal CO₂ pressure (P_ETCO ₂) increased from 45 (42–48) to 48 (46–58) mmHg with a reduction of only 1% in the arterial haemoglobin O₂ saturation (S_aO ₂). During control exercise (normal breathing resistance), muscle and brain ΔHbO₂ were not different from the resting levels, and only the leg muscle ΔHb increased (4 (–2–10) μM , P < 0.05). Moderate resistive breathing increased ΔHbO₂ of the intercostal and vastus lateralis muscles to 6 ± (–5–14) and 1 (–7–9) μM (P < 0.05), respectively, while muscle ΔHb was not affected. Cerebral ΔHbO₂ and ΔHb became elevated to 6 (1–15) and 1 (–1–6) μM by resistive breathing (P < 0.05). Resistive breathing caused an increased concentration of oxygenated haemoglobin in active muscles and in the brain. The results indicate that CO₂ influences blood flow to active skeletal muscle although its effect appears to be smaller than for the brain.     

Effects of whole body UV-irradiation on oxygen delivery from the erythrocyte

Summary In 16 healthy caucasian volunteers (mean age: 22.2 years) the influence of whole body UV-irradiation on the oxygen transport properties of erythrocytes was investigated. Four hours after irradiation with UV (using the minimal erythema dose, MED) no variation of haemoglobin concentration, hematocrit, mean corpuscular haemoglobin concentration, pH or standard bicarbonate could be found, whereas inorganic plasma phosphate (P_i), calcium, the intraeryhtrocytic 2,3-diphosphoglycerate (2,3-DPG), the activity of erythrocytic phosphofructokinase (PFK) and pyruvatekinase (PK) increased significantly. The half saturation tension of oxygen (P₅₀-value) tended to increase. The increase of P_i causes — via a stimulation of the glycolytic pathway — an increase in 2,3-DPG concentration and thus results in a shift of the oxygen dissociation curve. It is therefore possible to enhance tissue oxygenation by whole body UV-irradiation. Supported in part by the Forschungsf?rderungsbeitrag of Vorarlberg 1979 and a grant from Greiter AG, Weidling, Austria     

Intracapillary hemoglobin oxygen saturation and oxygen consumption in different layers of the left ventricular myocardium

Summary Oxygen consumption in subendocardial and subepicardial layers of left ventricular myocardium was studied. Oxygen consumption was calculated from regional perfusion data obtained by the microsphere technique and regional O₂ extraction derived from intracapillary HbO₂ saturation (i.c. HbsO₂). I.c. HbsO₂ data were obtained cryomicrophotometrically from shock-frozen, transmural tissue specimens removed from thoracotomized dogs. Left ventricular myocardial blood flow at the time of the specimen removal was 63±9 ml/min · 100 g. The ratio of subendocardial to subepicardial blood flow was 1.27 ±0.17. Coronary sinus blood oxygen saturation was 31±2% and left ventricular oxygen consumption was 8.4±1.1 ml/min · 100 g. A mean i.c. HbsO₂ of 47±18% was obtained. 23% of all measured i.c. HbsO₂ values were lower than the respective coronary sinus value. The mean subendocardial i.c. HbsO₂ (41±19%) was significantly lower than the mean subepicardial value (53±16%). From these data a ratio of subendocardial to subepicardial oxygen consumption of 1.57 was calculated. This result is in agreement with recent hypotheses, stating that myocardial fiber shortening and energy demands in deeper layers of left ventricle exceed those of superfical layers.Supported by Deutsche Forschungsgemeinschaft and by Stiftung Volkswagenwerk     

Effects of indomethacin and polyunsaturated fatty acid diet on exercise-induced hypoxaemia in master athletes

We have previously reported a reduction in exercise-induced hypoxaemia following polyunsaturated fatty acid supplementation (PUFA). Although this might have been explained by increases in membrane fluidity, a clear explanation could not be provided due to potentially confounding influences of series-2 prosta- glandin mediated effects resulting from PUFA. In this investigation, ten master athletes [mean age 48.1 (SEM 6) years, maximal oxygen uptake (V˙O_{2 max} ) 3.39 (SEM 0.21) l?·?min^?1] completed a maximal cycling test (Ctrl) which was repeated after the administration of 150 mg of indomethacin to inhibit prostaglandin synthesis, both before and after 6 weeks of 3.66-g PUFA?·?day^?1. Cardiorespiratory parameters were obtained simultaneously with brachial arterial blood sampling for partial pressure of oxygen in arterial blood (P _aO₂), partial pressure of carbon dioxide in arterial blood (P _aCO₂), pH, oxygen saturation in arterial blood and lactate concentration determinations. A significant decrease in P _aO₂ (mmHg) from rest [93 (SEM 1.5)] was observed for exercise intensities of more than 40% V˙O_{2 max} in Ctrl reaching 75.9 (SEM 2.1) at V˙O_{2 max} . PUFA resulted in a 5.0 (SEM 0.68) mmHg upward shift (P?P _aO₂–oxygen uptake relationship, reducing the difference in partial pressure of oxygen between alveolar air and arterial blood (P _(A?a)O₂) at V˙O_{2 max} [Ctrl 36 (SEM 1.6) vs PUFA 33 (SEM 2.2) mmHg] while P _aCO₂, remained unchanged. Indomethacin had no effect on either P _aO₂, ideal partial pressure of oxygen in alveolar gas or P _(A?a)O₂ in either Ctrl or after PUFA. In contrast, the fall in pH was significantly reduced after indomethacin while V˙CO₂, P _aCO₂ and lactacidaemia remained unchanged. These observations confirm an effect of PUFA on exercise P _aO₂ behaviour which does not appear to be mediated by the influence of a series-2 prostaglandin.     

Red blood cell pH,the Bohr effect,and other oxygenation‐linked phenomena in blood O2 and CO2 transport

Abstract The discovery of the S‐shaped O₂ equilibrium curve and the Bohr effect in 1904 stimulated a fertile and continued research into respiratory functions of blood and allosteric mechanisms in haemoglobin (Hb). The Bohr effect (influence of pH/CO₂ on Hb O₂ affinity) and the reciprocal Haldane effect (influence of HbO₂ saturation on H⁺/CO₂ binding) originate in the Hb oxy–deoxy conformational change and allosteric interactions between O₂ and H⁺/CO₂ binding sites. In steady state, H⁺ is passively distributed across the vertebrate red blood cell (RBC) membrane, and intracellular pH (pH_i) changes are related to changes in extracellular pH, Hb‐O₂ saturation and RBC organic phosphate content. As the Hb molecule shifts between the oxy and deoxy conformation in arterial‐venous gas transport, it delivers O₂ and takes up CO₂ and H⁺ in tissue capillaries (elegantly aided by the Bohr effect). Concomitantly, the RBC may sense local O₂ demand via the degree of Hb deoxygenation and release vasodilatory agents to match local blood flow with requirements. Three recent hypotheses suggest (1) release of NO from S‐nitroso‐Hb upon deoxygenation, (2) reduction of nitrite to vasoactive NO by deoxy haems, and (3) release of ATP. Inside RBCs, carbonic anhydrase (CA) provides fast hydration of metabolic CO₂ and ensures that the Bohr shift occurs during capillary transit. The formed H⁺ is bound to Hb (Haldane effect) while HCO₃^? is shifted to plasma via the anion exchanger (AE1). The magnitude of the oxylabile H⁺ binding shows characteristic differences among vertebrates. Alternative strategies for CO₂ transport include direct HCO₃^? binding to deoxyHb in crocodilians, and high intracellular free [HCO₃^?] (due to high pH_i) in lampreys. At the RBC membrane, CA, AE1 and other proteins may associate into what appears to be an integrated gas exchange metabolon. Oxygenation‐linked binding of Hb to the membrane may regulate glycolysis in mammals and perhaps also oxygen‐sensitive ion transport involved in RBC volume and pH_i regulation. Blood O₂ transport shows several adaptive changes during exposure to environmental hypoxia. The Bohr effect is involved via the respiratory alkalosis induced by hyperventilation, and also via the pH_i change that results from modulation of RBC organic phosphate content. In teleost fish, β‐adrenergic activation of Na⁺/H⁺ exchange rapidly elevates pH_i and O₂ affinity, particularly under low O₂ conditions.     

Effect of variations in blood hydrogen ion concentration on pulmonary gas exchange of artificially ventilated dogs

The effect of variation of blood hydrogen ion concentration on arterial and mixed venousP _{O 2},ideal alveolar-arterial O₂ pressure difference (P _AiO₂–P _aO₂),venous admixture (Q _s/Q _t), arterio-alveolar CO₂ pressure difference (a–A)D _{CO 2},physiological dead space to tidal volume ratio (V _D/V_T),cardiac output (Q _t) and mean pulmonary arterial pressure ( ) has been studied. Arterial and mixed venousP _{O 2}increased and (P _AiO₂–P _aO₂)decreased with increasing blood hydrogen ion concentration. No change in (Q _s/Q _t), (a–A)-D _{CO 2},V _D/V_T,Q _t and was observed.The effect of hydrogen ion concentration on arterial and mixed venousP _{O 2}and on (P _AiO₂–P _aO₂)is mainly due to a shift of the blood oxyhemoglobin dissociation curve (ODC), i.e. due to the Bohr effect. The upper part of the ODC is more flat in alkalosis (shift to the left) than in acidosis (shift to the right). Therefore the same end-capillary to arterial O₂ content difference results in a greater (P _AiO₂–P _aO₂)in alkalosis than in acidosis. Any factor influencing the slope of the upper part of the ODC is expected to affect the arterialP _{O 2}and the (P _AiO₂–P _aO₂)by this mechanism. Similarly any factor shifting the steep part of the ODC is expected to affect theP _{O 2}of the mixed venous blood.     

Direct determination of local oxygen consumption of the brain cortex in vivo

Summary A method is described to determine local oxygen consumption quantitatively in the brain cortex under in vivo conditions. Local oxygen consumption is calculated from the slope of local tissue P_{O 2} decrease during a few seconds of total ischemia of the brain for each second after the stop of circulation. The decrease of tissue P_{O 2} is recorded simultaneously at several measuring sites. To be independent of oxygen chemically bound to hemoglobin, tissue P_{O 2} values are raised above 100 Torr. The calculation of local oxygen consumption for each second during the short period of ischemia showed that the O₂ consumption remains constant only for a few seconds ranging from 5 to maximally 15 s at different locations. Then O₂ consumption decreases continuously although the tissue P_{O 2} values are still above the full saturation of hemoglobin. The rate of local oxygen consumption varies considerably at different measuring sites of the superficial layers of the brain cortex (cat). The mean value amounts to 3±1.5 ml O₂/100 g tissue and minute.     

The influence of PaO2, pH and SaO2 on maximal oxygen uptake

Influence of arterial oxygen pressure (P_aO₂) and pH on haemoglobin saturation (S_aO₂) and in turn on O₂ uptake (VO ₂) was evaluated during ergometer rowing (156, 276 and 376 W; VO _2max, 5.0 L min^?1; n = 11). During low intensity exercise, neither pH nor S_aO₂ were affected significantly. In response to the higher work intensities, ventilations (V_E) of 129 ± 10 and 155 ± 8 L min^?1 enhanced the end tidal PO₂ (P_ETO₂) to the same extent (117 ± 2 mmHg), but P_aO₂ became reduced (from 102 ± 2 to 78 ± 2 and 81 ± 3 mmHg, respectively). As pH decreased during maximal exercise (7.14 ± 0.02 vs. 7.30 ± 0.02), S_aO₂ also became lower (92.9 ± 0.7 vs. 95.1 ± 0.1%) and arterial O₂ content (C_aO₂) was 202 ± 3 mL L^?1. An inspired O₂ fraction (F_IO₂) of 0.30 (n = 8) did not affect V_E, but increased P_ETO₂ and P_aO₂ to 175 ± 4 and 164 ± 5 mmHg and the P_ETO₂–P_aO₂ difference was reduced (21 ± 4 vs. 36 ± 4 mmHg). pH did not change when compared with normoxia and S_aO₂ remained within 1% of the level at rest in hyperoxia (99 ± 0.1%). Thus, C_aO₂ and VO _2max increased to 212 ± 3 mL L^?1 and 5.7 ± 0.2 L min^?1, respectively. The reduced P_aO₂ became of importance for S_aO₂ when a low pH inhibited the affinity of O₂ to haemoglobin. An increased F_IO₂ reduced the gradient over the alveolar-arterial membrane, maintained haemoglobin saturation despite the reduction in pH and resulted in increases of the arterial oxygen content and uptake.     

Measurements of facilitated diffusion of oxygen in red blood cells at 37°C

Summary The steady state transfer of O₂ across thin layers of centrifuged red cells at 37°C was measured before and after saturation of the haemoglobin with CO. The measurements were taken at 107 Torr and 116 Torr average O₂ partial pressure difference, respectively.Before CO saturation the O₂ transfer was 64 percent higher than afterwards. The average difference of the O₂ saturation at both surfaces of the erythrocyte layer was 82%.The maximum of the facilitated O₂ diffusion by oxyhaemoglobin diffusion was calculated to be equal to the free diffusion which occurs at 100 Torr partial pressure difference.The rate of facilitated O₂ diffusion in red cells corresponds to a diffusion coefficient of the carrier (haemoglobin) of 5–6×10^–8 cm²/sec.Supported by the Deutsche Forschungsgemeinschaft.     

Transmural Oxygen Tension Gradients in Rat Cerebral Cortex Arterioles

Modified needle oxygen microelectrodes and vital microscopy were used to measure transmural oxygen tension gradients (PO₂) in pial arterioles with lumen diameters of 20–90  μm. A relationship between the magnitude of the transmural PO₂ gradient and arteriole wall tone was found: in control conditions, PO₂ gradients were 1.17 ± 0.06 mmHg/μm (n  = 40), while in conditions of arteriolar wall dilation the transmural PO₂ gradient decreased to 0.68 ± 0.04 mmHg/μm (p  <  0.001, n  = 38). These data provide the first measurements of transmural PO₂ gradients in pial arterioles of different calibers at different levels of vascular tone and have fundamental importance for assessing the role of arterial microvessels in tissue oxygen supply processes. The results obtained here provide evidence that oxygen consumption by the vessel wall is within the range characteristic of enveloping tissues and that oxygen consumption by the endothelial cell layer probably has no significant effect on the magnitude of the transmural PO₂ gradient. Translated from Rossiiskii Fiziologicheskii Zhurnal imeni I. M. Sechenova, Vol. 94, No. 4, pp. 394–405, April, 2008.     

Beeinflussung von Gasaustausch und Metabolismus durch unterschiedliche Hämodialyseverfahren

Summary We compared the effects of various dialysate composition on pulmonary and transdialyzer gas exchange in patients during hemodialysis. Under acetate hemodialysis there was a permanent loss of CO₂ (45–68 ml/min) into the dialysate resulting in a significant decrease of arterial pO₂, which can be explained by a reduced alveolar ventilation. The pulmonary oxygen uptake increased up to +20% during treatment, reflecting rising energy metabolism and possibly increased cardiopulmonary instability.Using different concentrates for bicarbonatehemodialysis we saw a moderate to clinical relevant uptake of CO₂ (40–60 ml/min) from the dialysate into the blood of the patients, cause the pCO₂ in the dialysate varied between 45 and 115 mmHg.Bicarbonate hemodialysis with high pCO₂-levels in the dialysate led to hyperventilation and markedly increased oxygen consumption. In critically ill hemodialysis patients the pathophysiologic effects on pulmonary gas exchange of either acetatehemodialysis and bicarbonatehemodialysis with high pCO₂ can explain the higher incidence of severe complications.

Herrn Professor Dr. F. Scheler zu seinem 65. Geburtstag gewidmet