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Binding of beta-naphthyl triphosphate to human adult hemoglobin accompanying deoxygenation. Investigated by simultaneous measurements of fluorescence, absorbance and partial pressure of oxygen.

Binding of a fluorescent allosteric effector, beta-naphthyl triphosphate (beta-NapP3), to human adult hemoglobin (HbA) at various levels of oxygen saturation were investigated by simultaneous measurements of fluorescence, absorbance and oxygen partial pressure. Amounts of beta-NapP3 bound to HbA were easily estimated from the fluorescence intensities of HbA solutions, because it was previously proved that the fluorescence of beta-NapP3 bound to HbA is completely quenched. Exchange reactions of the above fluorescent allosteric effector with 2,3-bisphosphoglycerate (DPG) were also examined at various levels of oxygen saturation. It was found that beta-NapP3 binds to deoxyHbA tetramer in the molar ratio of 2:1, and that one of the two beta-NapP3 competes with DPG. It was also found that beta-NapP3 binds to completely oxygenated HbA tetramer in the molar ratio of 1:1, and that the bound beta-NapP3 was not released by adding DPG. The binding affinity of beta-NapP3 for the noncompetitive site of completely oxygenated HbA, to which DPG does not bind, was smaller than that for the noncompetitive site of deoxyHbA, to which DPG also does not bind. Furthermore, the correlations between oxygen bindings by HbA and the bindings of beta-NapP3 to HbA in the intermediate stages of deoxygenation were investigated. It was revealed that HbA as a tetramer exists in three conformational states rather than simple two states as Monod, Wyman, and Changeux had proposed.

Binding Sites↗

Oxidative modification and antioxidant protection of human low density lipoprotein at high and low oxygen partial pressures.

Oxidative modification of low density lipoprotein (LDL) in the subendothelial space of the arterial wall has been implicated as an initial process in atherosclerosis. In vitro studies of LDL oxidation are usually done at ambient oxygen partial pressure (pO2; approximately 160 torr, or 21% O2), which is considerably higher than arterial tissue pO2 (30-70 torr, and as low as 20 torr, or 2.5% O2, in atherosclerotic lesions). In addition, beta-carotene acts as an efficient free radical scavenger only at low pO2. Therefore, we investigated the effects of high (20%) and low (2%) pO2 on the kinetics of LDL oxidation, and the effectiveness of beta-carotene compared to other physiological antioxidants in preventing LDL oxidation. At low pO2, the rate of Cu(2+)-induced oxidative modification of LDL was lower than at high pO2. Furthermore, at high pO2 there was a distinct lag phase preceding the propagation phase of lipid peroxidation in Cu(2+)-exposed LDL, as measured by cholesteryl ester hydroperoxide formation; in contrast, there appeared to be no distinct lipid peroxidation lag phase in LDL incubated with Cu2+ at low pO2. Elevating alpha-tocopherol levels in LDL about 5-fold resulted in significant antioxidant protection: the lipid peroxidation lag phase at high pO2 increased by 45% (from 58 +/- 11 to 84 +/- 3 min, P < 0.05), and the initial rate (0-1 h) of lipid hydroperoxide formation at low pO2 was reduced by 52% (from 11.6 +/- 1.9 to 5.6 +/- 1.0 nmol/mg LDL protein/h, P < 0.01). In contrast, increasing LDL beta-carotene levels about 6-fold did not inhibit LDL oxidation at either pO2. Most remarkably, low concentrations of ascorbic acid (30 microM) drastically reduced LDL oxidation, regardless of pO2: the lipid peroxidation lag phase at high pO2 increased more than 7-fold (from 46 +/- 11 min to > 360 min, P < 0.001), and at low pO2 no lipid hydroperoxides could be detected for at least 6 h of incubation. These results show that at low physiological pO2, Cu(2+)-induced LDL oxidation occurs at a significantly lower rate than at ambient pO2. At both high and low pO2, beta-carotene cannot inhibit LDL oxidation, whereas alpha-tocopherol has a moderate protective effect, and low physiological concentrations of ascorbic acid very strongly suppress LDL oxidation.

Antioxidants↗

Influence of arterial partial pressure of carbon dioxide on cerebral MRA in normal volunteers.

OBJECTIVE: Signal intensity of MR angiography (MRA) is influenced by the physiological factors of flowing blood in the vessels. We examined whether MRA can detect a cerebral hemodynamic change induced by reducing or elevating the arterial partial pressure of carbon dioxide (PaCO2). MATERIALS AND METHODS: Cerebral MRA was performed in six normal volunteers, each having three measurements during hyperventilation, normal breathing, and 7% CO2 inhalation. The MRA data were obtained by a 0.5 T wholebody scanner and a time-of-flight technique of three-dimensional GE imaging. In addition to the visual inspection, the signal intensity and the lengths of the middle cerebral artery (MCA) and posterior cerebral artery (PCA) were estimated in relation to PaCO2. RESULTS: The MRA appearances of major cerebral arteries were remarkably different depending on the breathing conditions. There was significant difference in the mean signal intensity (p < 0.01) and the mean length (p < 0.01) of the MCA and PCA between the hyperventilation and normal breathing trials. CONCLUSION: The MRA signal was sensitive to the changes in PaCO2 level of flowing blood. This phenomenon may result from changes in the velocity of blood flow in major cerebral arteries.

Administration, Inhalation↗

Partial pressure of oxygen in brain and peripheral nerve during damaging electrical stimulation.

The studies were performed to elucidate the mechanism underlying the neural damage which may occur during prolonged electrical stimulation of either brain tissue or peripheral nerve. The partial pressure of oxygen (pO2) was measured in the sciatic nerve and the cerebral cortex of adult cats before and during direct, local electrical stimulation of these neural tissues, using stimulus parameters capable of inducing neural injury. pO2 was monitored by the polarographic method, employing a platinum microelectrode inserted into the tissue adjacent to or beneath the stimulating electrode. In the sciatic nerve there was no marked change in intrafascicular pO2 in three cats upon initiation of the electrical stimulation. In a fourth animal intraneural pO2 increased briefly upon initiation of the stimulation. In no case did the intrafascicular compartment of nerves become significantly hypoxic. In the cerebral cortex, the start of stimulation was accompanied by a significant increase (approximately 12-15 Torr) in intracortical pO2 beneath the stimulating electrode, and pO2 remained at or above the pre-stimulus value for the duration of the stimulation. These results show that extracellular hypoxia is unlikely to be a significant factor in the neural injury induced in brain or peripheral nerve by prolonged electrical stimulation.

Animals↗

Changes in transcutaneous oxygen partial pressure as an index of response to inhaled methacholine in asthmatic patients.

Bronchoconstriction and hypoxemia have been reported to occur during airway challenges, but the correlation between changes in forced expiratory volume in 1 s (FEV1) and transcutaneous oxygen partial pressure (tcPO2) during methacholine provocation tests has not yet been established (to our knowledge). In 15 symptom-free atopic asthmatic patients and 5 normal subjects, variations in tcPO2 and FEV1 were simultaneously measured during inhalation of doubling methacholine concentrations; the drug concentrations causing a 20 percent decrease in control FEV1 and tcPO2 (PC20FEV1 and PC20tcPO2, respectively) were subsequently calculated. In patients, geometric mean PC20FEV1 and PC20TcPO2 were 1.31 (range, 0.16 to 5.19) and 1.26 (range, 0.29 to 5.82) mg/ml, respectively. In addition, in six patients, methacholine-induced fall in tcPO2 was accompanied by similar changes in arterial PO2. Methacholine inhalation caused no change in tcPO2 or FEV1 in normal subjects. The independent effects of deep breath tests and bronchoconstriction on PC20tcPO2 were studied in five patients challenged on two separate occasions, with and without FEV1 assessment; in these patients, PC20tcPO2 were similar on both the study days. The results indicate that, in asthmatic patients, methacholine-induced bronchoconstriction causes parallel decreases in FEV1 and tcPO2. The tcPO2 monitoring may serve as a tool in the assessment of airway hyperreactivity when active patient's cooperation is scarce.

Administration, Inhalation↗

Blood glucose reagent strip tests in the operating room: influence of hematocrit, partial pressure of oxygen, and blood glucose level--a comparison of the BM-test 1-44, BM-Accutest, and Satellite G reagent strip systems.

OBJECTIVE: The objective of our study was to assess the influence of hematocrit (HCT), partial pressure of oxygen (PO2), and blood glucose level upon results obtained with three different blood glucose reagent strip tests used in conjunction with the appropriate meter: BM-Test 1-44, BM-Accutest, and Satellite G. METHODS: Our study was designed as a consecutive sample study of patients undergoing coronary artery surgery. The setting was the hospital theater and intensive care unit. We conducted blood analysis for HCT, PO2 and blood glucose on 20 consecutive patients undergoing coronary artery surgery using three blood glucose reagent strip testing systems and a laboratory analysis of plasma glucose. RESULTS: All three blood glucose reagent strip tests showed a significant bias when compared with plasma glucose: BM-Test 1-44, 0.89 mmol/L; BM-Accutest, -1.27 mmol/L; Satellite G, 0.75 mmol/L (p < 0.05). The error found when using the Satellite G system was worse than that of either of the other two systems. Results obtained with the BM-Accutest strips were unaffected by PO2 (p = 0.745). Blood glucose value and HCT both had an influence on the results of all three blood glucose strip systems. CONCLUSIONS: Caution must be taken when using reagent strip systems in the operating room or intensive care setting because, of the three systems tested, all showed a significant bias, all were influenced by blood glucose level and HCT, and only the BM-Accutest reagent strips used with the Accutrend meter was unaffected by PO2.

Bias↗

Utility of capnography in predicting venous carbon dioxide partial pressure in sedated patients during outpatient oral surgery.

Twelve ASA class I patients scheduled for removal of third molars under intravenous sedation were included in the study. Samples for venous blood gas analysis were drawn every 5 minutes and the venous partial pressure of carbon dioxide was compared to the end-tidal CO2 recorded from a modified nasal cannula at the same time the samples were drawn. Correlation analysis was performed using the Pearson correlation coefficient. The overall correlation between end-tidal CO2 and PVCO2 was .54 (P = .0001). The results of the investigation indicate that through simple modifications of the end-tidal CO2 monitoring device, the correlation between end-tidal CO2 and serum PCO2 in a nonintubated patient can be improved.

Adolescent↗

Spinal epidural oxygen partial pressure and evoked spinal cord potential in relation to the severity of spinal ischemia during cross-clamping of the thoracic aorta.

Experiments were undertaken to determine the relationship between evoked spinal cord potential (ESP) and the partial pressure of oxygen in tissue in the epidural space (E-pO2) during aortic clamping. Eighteen adult mongrel dogs were studied as follows. In group I (n = 6), the descending thoracic aorta was clamped partially at the proximal site for 15 min to maintain the distal arterial pressure at 60, 40, and 20 mmHg consecutively at 15 min intervals. In group II (n = 6), the descending thoracic aorta was clamped proximally for 30 min. In group III (n = 6), the descending thoracic aorta was cross-clamped at proximal and distal sites for 30 min. Postoperative complete paraplegia was observed in 4 of 6 dogs in group III, but none in group II. The change in ESP with aorta cross-clamping was very mild in groups I and II. Transient increases and decreases in the ESP amplitude were observed in group III. The decrease of E-pO2 correlated well with the distal arterial pressure, and a rapid return to baseline of the E-pO2 was observed after declamping. The E-pO2 changed in response to spinal ischemia more rapidly than did ESP in all groups. The critical level of E-pO2 was 50 mmHg or a 40% decrease from baseline. Because the ESP reflects spinal function and the E-pO2 reflects spinal blood pressure, we propose that combined recording of ESP and E-pO2 would improve spinal monitoring during thoracic aortic surgery.

Animals↗

Oxygen partial pressure in outer layers of skin: simulation using three-dimensional multilayered models.

OBJECTIVE: Papillary loops in dermal papillae are believed to facilitate oxygen delivery to the germinal layer in the epidermis. The study aims to simulate the distribution of the oxygen partial pressure, pO2, in superficial layers of skin and to quantify oxygen supply from different sources. METHODS: A theoretical model that considered heterogeneity in tissue properties was developed based on the anatomical arrangement of the upper skin. Distribution of pO2 in tissues and in blood was solved numerically. Effects of the blood flow rate and the skin surface condition were investigated. RESULTS: Under normal blood flow rate and skin surface conditions, approximately one-quarter of the oxygen consumed in the upper skin came from papillary loops. Subpapillary plexus was the main supplier, which accounted for more than 60% of the total oxygen supply. Oxygen diffusion into the skin from the air was restricted to superficial regions of the germinal layer and accounted for approximately 10% of the total oxygen uptake. CONCLUSIONS: Papillary loops in dermal papillae facilitate oxygen delivery to the germinal layer from the circulation. The flow rate in papillary loops affects pO2 distribution in dermal papillae. In the epidermis, however, pO2 is strongly affected by skin surface conditions.

Biological Transport↗

Rate coefficients for the gas-phase reaction of OH radicals with dimethyl sulfide: temperature and O2 partial pressure dependence.

Rate coefficients for the gas-phase reaction of hydroxyl (OH) radicals with dimethyl sulfide (CH(3)SCH(3), DMS) have been determined using a relative rate technique. The experiments were performed under different conditions of temperature (250-299 K) and O(2) partial pressure (approximately 0 Torr O(2)-380 Torr O(2)), at a total pressure of 760 Torr bath gas (N(2) + O(2)), in a 336 l reaction chamber, using long path in situ Fourier transform (FTIR) absorption spectroscopy to monitor the disappearance rates of DMS and the reference compounds (ethene, propene and 2-methylpropene). OH was produced by the photolysis of H(2)O(2). The following Arrhenius expressions adequately describe the rate coefficients as a function of temperature (units are cm(3) molecule(-1) s(-1)): k = (1.56 +/- 0.20) x 10(-12) exp[(369 +/- 27)/T], for approximately 0 Torr O(2); (1.31 +/- 0.08) x 10(-14) exp[(1910 +/- 69)/T], for 155 Torr O(2); (5.18 +/- 0.71) x 10(-14) exp[(1587 +/- 24)/T], for 380 Torr O(2). The results are compared with previous investigations.

Chemical Phenomena↗

Exercise ventilation inefficiency and cardiovascular mortality in heart failure: the critical independent prognostic value of the arterial CO2 partial pressure.

AIMS: In chronic heart failure (CHF) patients, the ventilation (Ve) needed to eliminate metabolically produced CO(2) during exercise (i.e. the Ve/Vco(2) slope) is a strong prognosticator. Ve/Vco(2) slope determinants are the dead space-tidal volume (Vd/Vt) ratio and the arterial CO(2) partial pressure (Paco(2)). We aimed at defining the respective prognostic role of these two variables. METHODS AND RESULTS: One hundred and twenty-eight stable CHF patients (average left ventricular ejection fraction 34+/-10%) underwent cardiopulmonary exercise testing and blood gas analysis. The prognostic relevance of the Ve/Vco(2) slope, Vd/Vt, and Paco(2) at peak exercise was evaluated by the Kaplan-Meier approach with log-rank testing and by multivariate Cox regression analysis. During a mean period of 31.3+/-20 months, 24 patients died from cardiac causes. In univariate analysis, predictors of death included the use of anti-aldosterone drugs, low peak Vo(2), peak Ve/Vo(2), peak Paco(2) and high Ve/Vco(2) slope, and peak Vd/Vt. Multivariate analysis identified a low peak Paco(2) (<35 mmHg) as the strongest independent prognostic indicator [hazard ratio 4.65, 95% confidence interval (CI) (1.695-12.751), P=0.003] that primarily accounts for the Ve/Vco(2) slope prognostic power. CONCLUSION: These findings imply that regulatory mechanisms involved in the tight control of ventilatory command and blood gas tension, rather than lung function abnormalities, play a critical pathophysiological role in the exercise ventilation inefficiency of CHF patients.

Blood Gas Analysis↗

Relationship between the partial pressure of arterial oxygen and airflow limitation in children with cystic fibrosis.

To assess whether it would be possible to avoid repeated arterial blood sampling in children with cystic fibrosis, the relation between the forced expiratory flow at 25% to 75% of the vital capacity (FEF25%-75%) and the partial pressure of arterial oxygen (PaO2) was examined. The PaO2 and the logarithm of the FEF25%-75% (expressed as a percentage of that predicted) showed the strongest correlation (r = 0.89, p less than 0.001). Although this relation cannot be used when an accurate value for the PaO2 is required, it can sometimes be useful for determining the need for an arterial puncture.

Carbon Dioxide↗

The role of physiological oxygen partial pressures in lipid peroxidation. Theoretical considerations and experimental evidence.

The oxidative breakdown of membrane lipids, i.e. lipid peroxidation, is considered to be decisively involved in a number of toxicological and pathological processes including liver injury caused by iron overload and halogenated alkanes such as CCl4. Within the physiological oxygen partial pressure (PO2) range, i.e. at PO2 between 1 and 100 mmHg, lipid peroxidation depends on O2 in a complex manner. For instance, CCl4-induced lipid peroxidation exhibits a distinct maximum at PO2 of around 7 mmHg, and iron-induced lipid peroxidation shows marked differences in its O2 dependence between an early lag phase and a later phase of self-accelerating propagation. The O2 dependence of lipid peroxidation is either determined by the O2 dependence of initiation or the O2 dependence of propagation. Factors decisive for this are presented and the underlying alterations in the pattern of the peroxidation-related reactions delineated.

Animals↗

Measurement of oxygen partial pressure, its control during hypoxia and hyperoxia, and its effect upon light emission in a bioluminescent elaterid larva.

This study investigates the respiratory physiology of bioluminescent larvae of Pyrearinus termitilluminans in relation to their tolerance to hypoxia and hyperoxia and to the supply of oxygen for bioluminescence. The partial pressure of oxygen (P(O2)) was measured within the bioluminescent prothorax by in vivo electron paramagnetic resonance (EPR) oximetry following acclimation of larvae to hypoxic, normoxic and hyperoxic (normobaric) atmospheres and during periods of bioluminescence (during normoxia). The P(O2) in the prothorax during exposure to an external P(O2) of 15.2, 160 and 760 mmHg was 10.3+/-2.6, 134+/-0.9 and 725+/-73 mmHg respectively (mean +/- s.d., N=5; 1 mmHg=0.1333 kPa). Oxygen supply to the larvae via gas exchange through the spiracles, measured by determining the rate of water loss, was also studied in the above atmospheres and was found not to be dependent upon P(O2). The data indicated that there is little to no active control of extracellular tissue P(O2) within the prothorax of these larvae. The reduction in prothorax P(O2) observed during either attack-response-provoked bioluminescence or sustained feeding-related bioluminescence in a normoxic atmosphere was variable, but fell within the range 10-25 mmHg. The effect of hypoxic atmospheres on bioluminescence was measured to estimate the intracellular P(O2) within the photocytes of the prothorax. Above a threshold value of 50-80 mmHg, bioluminescence was unaffected by P(O2). Below this threshold, an approximately linear relationship between P(O2) and bioluminescence was observed. Taken together with the extracellular P(O2) measurements, this suggests that control of P(O2) within the photocyte may occur. This work establishes that EPR oximetry is a valuable technique for long-term measurement of tissue P(O2) in insects and can provide valuable insights into their respiratory physiology. It also raises questions regarding the hypothesis that bioluminescence can have a significant antioxidative effect by reduction of prothorax P(O2 )through oxygen consumption.

Animals↗

The effect of oxygen partial pressure on protein synthesis and collagen hydroxylation by mature periodontal tissues maintained in organ cultures.

Mature periodontal tissues from adult-mouse first mandibular molars were cultured in a continuous-flow organ-culture system which allowed the regulation of both ascorbic acid concentration and pO(2) (oxygen partial pressure). Protein synthesis was measured by analysing the incorporation of [(3)H]proline into collagenous and non-collagenous proteins during the last 24h of a 2-day culture. At low pO(2) [16.0kPa (approx. 120mmHg)] approx. 60% of protein-incorporated [(3)H]proline was found in collagenous proteins. However, it was evident that this collagen was considerably underhydroxylated. At high pO(2) [56.0kPa (approx. 420mmHg)], both the amount of collagen deposited in the tissues and the degree of hydroxylation were increased considerably. In contrast, no significant effect on non-collagenous protein was observed. Tissues cultured at low pO(2) for the first 48h were unable to respond to a subsequent increase in pO(2) during the last 24h. Analysis of pepsin-solubilized collagen alpha-chains labelled with [(14)C]glycine demonstrated the synthesis of both type-I and type-III collagens by explants cultured for 48h at high pO(2). Type-III collagen comprised 20-30% of the radioactivity in alpha-chains in both the periodontal ligament and the tissues of the alveolar process. The pattern of protein synthesis in the alveolar tissues at high pO(2) was similar to that observed in these tissues in vivo. However, in the cultured periodontal ligament the proportions of non-collagenous proteins and type-III collagens were increased in comparison with the tissue in vivo.

Alveolar Process↗

Biphasic changes in tissue partial pressure of oxygen closely related to localized neural activity in guinea pig auditory cortex.

An understanding of the local changes in cerebral oxygen content accompanying functional brain activation is critical for making a valid signal interpretation of hemodynamic-based functional brain imaging. However, spatiotemporal relations between changes in tissue partial pressure of oxygen (Po2) and induced neural activity remain incompletely understood. To characterize the local Po2 response to the given neural activity, the authors simultaneously measured tissue Po2 and neural activity in the identical region of guinea pig auditory cortex with an oxygen microelectrode (tip < 10 microm) and optical recording with voltage-sensitive dye (RH 795). In addition, a laser displacement gauge and a laser-Doppler flowmeter were used to monitor the spatial displacement and regional cerebral blood flow, respectively, in the Po2 measurement region. In the activated region, tissue Po2 initially decreased during the approximately 3-seconds after the onset of acoustic stimuli, and then increased during the next approximately 5 seconds. Such biphasic changes are consistently found in cortical layers I to IV. In addition, amplitude of the biphasic change was closely related to detected peak height of the optical signal changes. The results suggest that the initial decrease in tissue Po2 is coupled to the induced neural activity and depends on response time of local increase in cerebral blood flow.

Acoustic Stimulation↗

[The influence of arterial partial pressure of co2 and of the arterial value of ph on endogenous catecholamines during extracorporal circulation in regard to oxygen consumption of the whole body (author's transl)].

Ten patients with coronary heart diseases were studied during total hypothermic extracorporal circulation relating changes of the endogenous catecholamines epinephrine and nor-epinephrine to arterial partial pressure of CO2 and to the arterial value of pH. Both of the catecholamines increased significantly during respiratory or metabolic acidosis whereas respiratory or metabolic alkalosis was accompanied by significantly lower catecholamine levels in blood. The changes in total peripheral resistance due to the endogenous blood levels of catecholamines depended proprotionally. Total peripheral resistance increased significantly due to increasing arterial level of both of the catecholamines. The results are discussed in consideration of oxygen consumption of the whole body during extracorporal circulation. It is known that the decrease of oxygen consumption of the whole body due to acidosis and due to an increased total peripheral resistance is accompanied by high catecholamine levels in blood. Increased hypothermic sympatho-adrenal activity during extracorporal circulation should not in any case cause in increase of oxygen consumption of the whole body.

Acidosis↗

End-tidal partial pressure of carbon dioxide does not accurately reflect PaCO2 in rabbits treated with acetazolamide during anaesthesia.

Acetazolamide, a carbonic anhydrase inhibitor, may cause significant disturbances in carbon dioxide transport and elimination. In this study, end-tidal carbon dioxide monitoring has been used to study the correlation between arterial carbon dioxide (PaCO2) and end-tidal carbon dioxide partial pressure (PE'CO2) in rabbits treated with acetazolamide. A significant difference in (PaCO2-PE'CO2) developed immediately after administration of acetazolamide and persisted for more than 2 h. It is concluded that PE'CO2 did not reflect accurately PaCO2 and the ventilatory status of the rabbit which received acetazolamide within 2 h.

Acetazolamide↗