The oxygen-carrying flask: a representational transform of the oxygen dissociation curve of hemoglobin.

The teaching of oxygen transport by hemoglobin is supported by a graphic depiction of the sigmoid O2 dissociation curve of hemoglobin. However, a reconstruction of the same curve into an alternate paradigm, the "O2-carrying flask," affords a visual demonstration of the significance of its sigmoid shape and the implications of its shifts, which should be useful in elucidating certain aspects of O2 transport to undergraduate students of physiology. This article provides a mathematical justification for the flask design.

Mechanism of reduction in alveolar-arterial PO2 difference by helium breathing in the exercising horse

Previous work has shown that replacing N2 in air with He at the same inspired O2 fraction reduces the exercise-induced alveolar-arterial PO2 difference (AaPO2) in horses but has provided no mechanism explaining this effect. We sought to distinguish among possible causes by using the multiple inert gas elimination technique. Six horses were studied on a high-speed treadmill while they breathed either ambient air or normoxic He-O2. O2 uptake reached 138.0 ml.min-1.kg-1 and was not affected by He-O2. Temperature-corrected arterial PO2 was 76.7 Torr (air) and 86.9 Torr (He-O2) (P < 0.01). Corresponding AaPO2 was 22.3 and 15.9 Torr, respectively (P < 0.01). Mean AaPO2 predicted from ventilation-perfusion inequality did not change with He-O2 (12.7 Torr with air and 11.9 Torr with He-O2). Mean arterial PCO2 was 50.1 Torr with air and 44.1 Torr with He-O2 (P < 0.01); minute ventilation and tidal volume were correspondingly higher by 140 l/min and 1.0 liter, respectively, with He-O2. Pulmonary O2 diffusing capacity, cardiac output, and all ventilation-perfusion dispersion indexes did not change with He-O2. Intrapulmonary shunt was insignificant. Higher ventilation with He-O2 explained only approximately 4 Torr of the 10-Torr rise observed in arterial PO2. The remainder (and the corresponding fall in AaPO2) was due to more complete diffusion equilibration as a consequence of the higher minute ventilation and thus alveolar PO2, which reduced the average slope of the O2 dissociation curve, thereby increasing the ratio of diffusive to perfusive conductance.

Enhanced oxygenation in vivo by allosteric inhibitors of hemoglobin saturation

The in vivo effects on hemoglobin (Hb)-O2 affinity and tissue PO2 were investigated after intraperitoneal administration of 2-[4-(((dichloroanilino)-carbonyl)methyl)phenoxyl]-2-methyl propionic acid (RSR4; 150 mg/kg) or its 3,5-dimethyl derivative (RSR13; 300 mg/kg) in C3Hf/Sed mice. The Hb-O2 dissociation curve was plotted from tail vein blood samples using an O2 dissociation analyzer before and up to 160 min after compound administration. Twenty to 40 min after injection, the PO2 at 50% saturation of hemoglobin (Hb P50) increased by a mean of 25% (range 18-31%) after RSR4 and 53% (range 36-76%) after RSR13. Tissue PO2 was continuously measured using an O2 microelectrode in thigh muscle before and up to 40 min after RSR4 or RSR13 injection. Twenty to 40 min after administration, tissue PO2 increased by a mean of 78% (range 30-127%) after RSR4 and 66% (range 39-97%) after RSR13 administration in anesthetized mice. No change in tissue PO2 was seen in anesthetized controls.

Muscle maximal O2 uptake at constant O2 delivery with and without CO in the blood

In the present study we investigated the effects of carboxyhemoglobinemia (HbCO) on muscle maximal O2 uptake (VO2max) during hypoxia. O2 uptake (VO2) was measured in isolated in situ canine gastrocnemius (n = 12) working maximally (isometric twitch contractions at 5 Hz for 3 min). The muscles were pump perfused at identical blood flow, arterial PO2 (PaO2) and total hemoglobin concentration [( Hb]) with blood containing either 1% (control) or 30% HbCO. In both conditions PaO2 was set at 30 Torr, which produced the same arterial O2 contents, and muscle blood flow was set at 120 ml.100 g-1.min-1, so that O2 delivery in both conditions was the same. To minimize CO diffusion into the tissues, perfusion with HbCO-containing blood was limited to the time of the contraction period. VO2max was 8.8 +/- 0.6 (SE) ml.min-1.100 g-1 (n = 12) with hypoxemia alone and was reduced by 26% to 6.5 +/- 0.4 ml.min-1.100 g-1 when HbCO was present (n = 12; P less than 0.01). In both cases, mean muscle effluent venous PO2 (PVO2) was the same (16 +/- 1 Torr). Because PaO2 and PVO2 were the same for both conditions, the mean capillary PO2 (estimate of mean O2 driving pressure) was probably not much different for the two conditions, even though the O2 dissociation curve was shifted to the left by HbCO. Consequently the blood-to-mitochondria O2 diffusive conductance was likely reduced by HbCO.(ABSTRACT TRUNCATED AT 250 WORDS)

Human whole-blood oxygen affinity: effect of temperature

phe effect of temperature changes on human whole-blood O2 affinity was measured in the blood of six healthy donors over almost the entire O2 saturation (SO2) range (1–99%). The results showed that temperature has no influence on the shape of the O2 dissociation curve, implying that the temperature coefficient (delta log PO2/delta T) is independent of SO2. Simultaneous measurements of the total (proton) Haldane factor (delta[HbH]/[delta HbO2]) at the five temperatures under study (22, 27, 32, 37, and 42 degrees C) revealed that this factor depends on temperature. The liberation of protons from hemoglobin appeared to be linear with respect to changes in SO2. We therefore conclude that the (proton) Bohr factor (H+ factor) is dependent on temperature over the entire SO2 range in the same way as previously described for SO2 = 50%. The exothermic oxygenation reaction in whole blood was accompanied by a heat evolution (delta HO2) of 42.7 kJ/mol (monomeric) hemoglobin.

Micromethod for dynamic determination of O2 dissociation curves using a PO2 electrode

A nonspectrophotometric method is described for measurement of the O2 dissociation curve and O2 capacity of a 50-microliter sample of fluid. PO2 is recorded by a microprocessor as the sample is oxygenated and then deoxygenated by exposure to isocapnic gas mixtures across a gas-permeable membrane. The time course of deoxygenation and the O2 conductance of the membrane are used in calculating the O2 capacity of the sample and the dissociation curve. The method is sensitive and is best suited to samples of low O2 capacity and affinity. Measurements on buffer-diluted human blood agree with standard values.

Effect of increased blood oxygen affinity on skeletal muscle surface oxygen pressure fields

A chronic left displacement of the blood O2 dissociation curve (ODC) was achieved in rats by administering cyanate over a period of 14 days. Control rats received NaCl. An acute left displacement of the ODC was achieved by exchange transfusion with bisulfite-treated erythrocytes. Control rats for this series received an exchange transfusion with fresh heparinized blood. In both series, skeletal muscle surface O2 pressure fields (expressed as PO2 histograms) were measured with the rats anesthetized, curarized, and artificially ventilated. The animals with chronically left-shifted ODC had normal PO2 histograms (for definition see DISCUSSION) when breathing air; during hypoxia (FIO2 0.12) four of the eight experimental and three of the seven control animals developed abnormal histograms, and all animals had normal histograms on return to air breathing. The majority, but not all, of the animals that were to receive exchange transfusions of left-shifted ODC blood had normal histograms before the transfusion, which caused some to become abnormal and others to become normal. Similar results were obtained in the control animals that received normal blood. The results do not provide evidence for an adverse effect of a left-shifted ODC on muscle tissue oxygenation.