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Simultaneous determination of hemoglobin derivatives, oxygen content, oxygen capacity, and oxygen saturation in 10 microliters of whole blood.

We describe a new method for simultaneous determination of four hemoglobin derivatives (deoxyhemoglobin, Hb; oxyhemoglobin, HbO2; methemoglobin, Hb+; and carbon monoxide hemoglobin, HbCO) and total oxygen content in 10 microliters of whole blood. Percentage HbO2, HbCO, Hb+, total hemoglobin (Hbt), and oxygen capacity can also be obtained from the experimental data by simple calculations. Total analysis time is 1 min. Blood is diluted 100-fold with a buffer contained in a quasi-anaerobic cuvette, where simultaneous measurements of oxygen pressure (by a po2 electrode) and adsorbance (at 497, 565, and 620 nm) are made. The decrease of oxygen pressure, as recorded by the oxygen electrode, is proportional to the amount of deoxyhemoglobin. The concentrations of HbO2, HbCO, and Hb+ can be obtained from absorbance measurements at the specified wavelengths. The new method eliminates the use of short-path optical cells and, due to the low sample volume requirement, makes possible the automated measurement of hemoglobin derivatives and oxygen saturation in arterialized capillary blood.

Carboxyhemoglobin↗

Oxygen delivery, oxygen consumption and hemoglobin-oxygen affinity in acute myocardial infarction.

The interrelations of oxygen delivery (DO2), oxygen consumption (VO2) and hemoglobin-oxygen affinity assessed by P50 were investigated in 43 patients with acute myocardial infarction. As DO2 declined due to low cardiac output, a significant decrease in VO2 (r = 0.75, p less than 0.001) and a significant increase in P50 (r = -0.74, p less than 0.001) were observed. In the DO2 range between 300 and 450 ml/min/m2, in which the DO2 of 32 survivors and 11 nonsurvivors overlapped, the P50 of nonsurvivors was significantly higher than that of survivors (31.5 +/- 1.6 vs 27.9 +/- 1.5 torr, p less than 0.001), but there were no significant differences in any other oxygen transport variable. As a result of differences in P50, VO2 in this range was significantly higher in nonsurvivors compared to survivors (169 +/- 17 vs 148 +/- 13 ml/min/m2, p less than 0.001). These data suggest that a normal or increased VO2 alone does not ensure survival in patients with acute myocardial infarction, and increased P50 leads to an increase in VO2. Nevertheless, the interpretation of an increased P50 in patients with acute myocardial infarction must be made with caution, even with adequate DO2 and VO2, because it may imply a precarious oxygen transport/requirement balance in peripheral tissue and, hence, a fatal outcome.

Aged↗

Hyperbaric oxygenation for experimental bladder tumor. I. Tissue oxygen tension of the rabbit bladder during hyperbaric oxygenation.

Although considerable advances have been made in the application of hyperbaric oxygenation (HBO) on tumor treatment in the recent past, many difficulties persist due to conflicting results and the understanding of its mechanism. We tested whether HBO treatment in clinical use could really influence the tissue concentration of oxygen in bladder or circulatory condition in animals. Eleven rabbits were treated with 1-3 atmospheric absolute pressures under an environment of air saturating 30-35% of oxygen for 90 min. Ten control animals were placed in the same chamber without providing HBO treatment. The tissue oxygen pressure in trigone or dome of the in HBO-treated group was significantly higher than that of the control group. A similar tendency was also noted in the arterial oxygen concentration to a greater extent, while regional blood flow in the bladder, mean arterial blood pressure and plasma volume were not significantly changed following HBO treatment. The use of HBO appears to offer some possibilities for the treatment of bladder tumor in the future.

Animals↗

Postnatal follow-up of the oxygenation index, arterial to alveolar oxygen tension ratio and alveolar arterial oxygen tension difference values in neonates with the respiratory distress syndrome treated with conventional ventilatory support.

Recent development of sophisticated intensive care technique for use in newborn infants with the respiratory distress syndrome (RDS) has resulted in changes in the therapeutic strategies and moved the problem of neonatal survival into the realm of new therapeutic realities. At present, the mechanical ventilation methods form an integral part of the intensive care strategy of infants with RDS. They have come to the forefront of infant care because of their successful use in ventilatory support and children survival where other therapeutic modalities have failed. The present prospective observational longitudinal study was designed to assess the real-time convenience, reliability and accuracy of the changes in the oxygenation index (OI), arterial-to-alveolar oxygen tension ratio (a/A PO2) and alveolar-arterial oxygen gradient (A-a)DO2 in ventilator-dependent neonates with RDS, to analyze their feasibility and potential information yield in oxygen inhalation therapy as well as their prognostic implications and predictive value. Twenty neonates with RDS, heralded by respiratory failure which necessitated the initiation of oxygen inhalation therapy and ventilatory support within 24 hours of birth, were enrolled in the study. Ten of the infants survived and the remaining ten died. OI, (a/A PO2) and (A-a)DO2 were followed up sequentially and thoroughly analyzed as the primary outcome measures of the study. The indices were calculated on the basis of the complete monitoring of the ventilatory equipment parameters and acid-base status carried out on an hourly basis. Our results show that: 1. The combination of three indexes (OI, (a/A)PO2 and (A-a)DO2 we propose is a useful discriminating predictor of neonatal lung maturity reflecting arterial blood gas status in ventilator-dependent neonates with RDS. 2. The indices detect the efficacy of the modern conventional ventilatory support with real-time convenience and reliable accuracy forming the cornerstone of clinical decision-making in RDS neonatal intensive care and allowing timely corrections of the ventilatory equipment parameters. 3. The prospective follow-up of these indices improves the predictive value as compared to any single test of neonatal lung maturity and has important prognostic implications in the management of neonates with RDS.

Humans↗

Effects of 100% oxygen and a mixture of oxygen and air on oxygen saturation in the immediate postoperative period in children.

Arterial oxygen saturation during transportation of children from the operating room to the recovery room and in the recovery room was monitored in two groups of patients, one given 100% oxygen at the end of anesthesia, the other given a 50:50 mixture of oxygen and air. The oxygen-air group had a statistically significantly higher incidence of hypoxemic episodes. Preoxygenation with 100% oxygen before transfer from the operating room reduces the incidence of hypoxemia in children.

Adolescent↗

Database of normal human cerebral blood flow, cerebral blood volume, cerebral oxygen extraction fraction and cerebral metabolic rate of oxygen measured by positron emission tomography with 15O-labelled carbon dioxide or water, carbon monoxide and oxygen: a multicentre study in Japan.

Measurement of cerebral blood flow (CBF), cerebral blood volume (CBV), cerebral oxygen extraction fraction (OEF) and cerebral metabolic rate of oxygen (CMRO(2)) by positron emission tomography (PET) with oxygen-15 labelled carbon dioxide (C(15)O(2)) or (15)O-labelled water (H(2)(15)O), (15)O-labelled carbon monoxide (C(15)O) and (15)O-labelled oxygen ((15)O(2)) is useful for diagnosis and treatment planning in cases of cerebrovascular disease. The measured values theoretically depend on various factors, which may differ between PET centres. This study explored the applicability of a database of (15)O-PET by examining between-centre and within-centre variation in values. Eleven PET centres participated in this multicentre study; seven used the steady-state inhalation method, one used build-up inhalation and three used bolus administration of C(15)O(2) (or H(2)(15)O) and (15)O(2). All used C(15)O for measurement of CBV. Subjects comprised 70 healthy volunteers (43 men and 27 women; mean age 51.8+/-15.1 years). Overall mean+/-SD values for cerebral cortical regions were: CBF=44.4+/-6.5 ml 100 ml(-1) min(-1); CBV=3.8+/-0.7 ml 100 ml(-1); OEF=0.44+/-0.06; CMRO(2)=3.3+/-0.5 ml 100 ml(-1) min(-1). Significant between-centre variation was observed in CBV, OEF and CMRO(2) by one-way analysis of variance. However, the overall inter-individual variation in CBF, CBV, OEF and CMRO(2) was acceptably small. Building a database of normal cerebral haemodynamics obtained by the(15)O-PET methods may be practicable.

Blood Volume↗

Comparison of the effects of controlled ventilation with 100% oxygen, 50% oxygen in nitrogen, and 50% oxygen in nitrous oxide on responses to venous air embolism in pigs.

In this randomized, experimental study in 18 pigs, we have investigated the effects of inspiratory air in oxygen, 100% oxygen and 50% nitrous oxide in oxygen on the detection and consequences of venous air embolism. Each animal was tested with injections of 1.0 ml kg-1 and 2.0 ml kg-1 of air. All animals, except one in the nitrous oxide group, survived the air emboli. Systolic and diastolic arterial pressures decreased significantly in all groups after both injections of air. Pulmonary diastolic pressures increased most in the nitrous oxide group. End-tidal concentration of carbon dioxide decreased significantly in all groups after air injections. The difference in concentration of oxygen in the inspiratory and expiratory gas (O2 (I-E)) was lowest in the air group after both injections of air. On the basis of our studies we suggest that nitrous oxide should not be used during surgery associated with an increased risk of venous air embolism.

Anesthetics, Inhalation↗

Dependence of oxygen consumption on oxygen delivery in children with hyperdynamic septic shock and low oxygen extraction.

We studied the effect of increasing systemic oxygen delivery (DO2) by packed RBC (PRBC) transfusion on oxygen consumption (VO2) in children with hyperdynamic septic shock. After routine resuscitation with volume loading and pharmacologic support, patients were studied if they had significant derangements of oxygen transport variables defined as: baseline VO2 less than 180 ml/min.m2 and oxygen extraction (O2 extr) less than 24%. Eight studies were performed. PRBC transfusion increased DO2 from 636 +/- 167 to 828 +/- 266 ml/min.m2 (p less than .01) without increasing cardiac index (5.2 +/- 1.3 vs. 5.0 +/- 1.4 L/min.m2). VO2 increased from 112 +/- 36 to 157 +/- 60 ml/min.m2 (p less than .01) while O2 extr was unchanged (18 +/- 3% vs. 19 +/- 6%). Despite initial low O2 extr, VO2 can be increased in pediatric septic shock by a further increase in DO2. Since VO2 correlates with survival, one should consider enhancing DO2 further despite initial low O2 extr and high DO2. Effects on morbidity and mortality require further study.

Adolescent↗

Analysis of the interrelationships of non-nutrient blood flow, oxygen delivery, oxygen consumption, and the ratio of oxygen delivery/oxygen consumption based on a mathematical model of non-nutrient blood flow.

A mathematical model for total body non-nutrient blood flow has been presented. This is a gross model that will show effective non-nutrient blood flow. It shows how NNBF can occur in the setting of decreased oxygen delivery. The implications of this model on the interrelationships of oxygen delivery, oxygen consumption, the ratio of oxygen delivery/oxygen consumption, and NNBF are discussed.

Acidosis↗

Blood oxygen tension and oxyhemoglobin saturation in hypoxemia due to right to left shunt or low inspired oxygen concentration. An experimental study of the effects of changes in blood oxygen affinity.

Oxygen tension, oxyhemoglobin saturation, and pH were measured in arterial and in venous blood from heart, brain, kidney, liver, gut and pulmonary artery in anesthetized hypoxemic dogs during a reduction of blood oxygen affinity due to increasing acidosis caused by the administration of CO2 and NH4Cl (pH range 7.40-6.80). In dogs with hypoxemia due to right to left shunt (anastomosis between inferior vena cava and left atrium), a reduction in blood oxygen affinity was followed by increasing Pao2 and Pvo2 at unchanged Sao2. In dogs with hypoxemia caused by alveolar hypoxia, or a combination of alveolar hypoxia and right to left shunt, a reduction of blood oxygen affinity was followed by arterial and venous desaturation at unchanged Pao2 values. Infusions of sodium bicarbonate or blood transfusions with reduced 2,3-diphosphoglycerate (2,3-DPG)-concentrations, if given to patients suffering from hypoxemia due to right to left shunt, may reduce the Pao2. Such therapy should be prescribed with caution.

Acidosis↗

Tissue oxygenation in hemorrhagic shock measured as transcutaneous oxygen tension, subcutaneous oxygen tension, and gastrointestinal intramucosal pH in pigs.

BACKGROUND AND METHODS: Tissue oxygenation, measured in peripheral tissue as transcutaneous PO2 (PtCO2) and subcutaneous PO2, was compared with the oxygenation in GI mucosa, which was measured as intramucosal wall pH (pHi), during experimental hemorrhagic shock and resuscitation in pigs. The pigs were hemorrhaged stepwise to a BP of 80 and 45 mm Hg, followed by retransfusion. PtCO2 was measured in the groin and subcutaneous PO2 was measured in the hip region. Intraluminal PCO2 was measured in the stomach, in the small intestine, and the sigmoid colon using silicone catheters. A simultaneous determination of arterial blood HCO3 concentration allowed pHi to be calculated using Henderson-Hasselbalch equation. Cardiac output was determined by thermodilution, and oxygen delivery (DO2) was calculated. RESULTS: Early indications of shock were decreases in PtCO2 and intestinal pHi (p less than .01). All measured variables decreased at the second step of bleeding. PtCO2 and subcutaneous PO2 was correlated to DO2 through the entire experiment (r2 = .25 and .49, respectively). Also, the pHi of the small intestine and the sigmoid colon correlated with DO2 (r2 = .36 and .25, respectively). PtCO2 and subcutaneous PO2 correlated with pHi in the small intestine and sigmoid colon. CONCLUSIONS: PtCO2 and pHi in the small intestine and sigmoid colon were the variables that most rapidly indicated blood volume loss. Subcutaneous PO2 and PtCO2, and small intestine and sigmoid colon pHi were correlated to total body oxygen transport. Peripheral tissue perfusion followed intestinal perfusion to some extent.

Animals↗

Alternative oxygen-dependent and oxygen-independent ribonucleotide reductases in Streptomyces: cross-regulation and physiological role in response to oxygen limitation.

Ribonucleotide reductases (RNRs) catalyse the conversion of ribonucleotides to deoxyribonucleotides and are essential for de novo DNA synthesis and repair. Streptomyces spp. contain genes coding for two RNRs. We show here that the Streptomyces coelicolor M145 nrdAB genes encoding an oxygen-dependent class I RNR are co-transcribed with nrdS, which encodes an AraC-like regulatory protein. Likewise, the class II oxygen-independent RNR nrdJ gene forms an operon with a likely regulatory gene, nrdR, which encodes a protein possessing an ATP-cone domain like those present in the allosteric activity site of many class Ia RNRs. Deletions in nrdB and nrdJ had no discernible effect on growth individually, but abolition of both RNR systems, using hydroxyurea to inactivate the class Ia RNR (NrdAB) in the nrdJ deletion mutant, was lethal, establishing that S. coelicolor possesses just two functional RNR systems. The class II RNR (NrdJ) may function to provide a pool of deoxyribonucleotide precursors for DNA repair during oxygen limitation and/or for immediate growth after restoration of oxygen, as the nrdJ mutant was slower in growth recovery than the nrdB mutant or the parent strain. The class Ia and class II RNR genes show complex regulation. The nrdRJ genes were transcribed some five- to sixfold higher than the nrdABS genes in vegetative growth, but when nrdJ was deleted, nrdABS transcription was upregulated by 13-fold. In a reciprocal experiment, deletion of nrdB had little effect on nrdRJ transcription. Deletion of nrdR caused a dramatic increase in transcription of nrdJ and to a less extent nrdABS, whereas disruption of cobN, a gene required for synthesis of coenzyme B12 a cofactor for the class II RNR, caused similar upregulation of transcription of nrdRJ and nrdABS. In contrast, deletion of nrdS had no detectable effect on transcription of either set of RNR genes. These results establish the existence of control mechanisms that sense and regulate overall RNR gene expression.

Amino Acid Sequence↗

Compliance, alveolar-arterial oxygen difference, and oxygenation index changes in patients managed with extracorporeal membrane oxygenation.

Eighteen patients with meconium aspiration syndrome who failed conventional management were treated with extracorporeal membrane oxygenation (ECMO) for reversible respiratory failure. Dynamic lung compliance measurements were made prior to, during, and after ECMO support. P(A-a)O2 and oxygenation index (OI) measurements were calculated prior to and after ECMO support. Lung compliance decreased significantly comparing before-ECMO to during-ECMO, and increased significantly comparing during- to after-ECMO, but not comparing before- to after-ECMO measurements. P(A-a)O2 and OI decreased significantly from before to after ECMO. The improvement in oxygenation allowing removal from ECMO does not appear to be related to improved pulmonary mechanics, but may rather be secondary to increased effective pulmonary capillary blood flow.

Extracorporeal Membrane Oxygenation↗

[A comparison of the effects of 50 % oxygen combined with CPAP to the non-ventilated lung vs. 100 % oxygen on oxygenation during one-lung ventilation].

OBJECTIVE: In a prospective, randomised, double-blind study the effects of FiO (2) of 0,5 with CPAP and a FiO (2) of 1.0 without CPAP on oxygenation and pulmonary shunt during one-lung ventilation (OLV) were examined. METHODS: In 20 patients undergoing thoracotomy (ASA II/III) two sequential ventilation methods were used during OLV: a) FiO (2) of 1.0 (OLV-100) and b) a FiO (2) of 0.5 in N (2)O combined with CPAP of 5 cm H (2)O to the non-ventilated lung (OLV-CPAP), whereby the sequence in 10 patients was OLV-CPAP followed by OLV-100; and the opposite in the remaining 10 patients. Operating conditions were graded by the surgeon. RESULTS: OLV-CPAP was associated with a better oxygenation and a lower shunt compared to OLV-100 (paO (2) : 198 +/- 40 mmHg vs 181 +/- 38 mmHg; p < 0.05 and Qs/Qt: 30 +/- 6 % vs. 34 +/- 8 %; p < 0.01, respectively). The different sequence of the ventilation methods did not cause significant differences in the results. The surgical conditions were not impaired by the CPAP of 5 cm H (2)O. CONCLUSION: The application of low FiO (2) with CPAP provided a better oxygenation and a lower pulmonary shunt during the OLV compared to high FiO (2) without CPAP.

Aged↗

Tissue oxygen saturation measured by near infrared spectrophotometry correlates with arterial oxygen saturation during induced oxygenation changes in neonates.

The aim of this study was to compare quantitatively the changes in tissue oxygen saturation (TOS), determined by two algorithms (TOSc and TOSa) based on near-infrared spectrophotometry, to the changes in arterial oxygen saturation (SaO2) measured by pulse oximetry. TOSc is an algorithm derived by the manufacturer (Critikon) based on a modified Beer-Lambert law; TOSa, our own algorithm, uses the diffusion approximation of light transport for the semi-infinite boundary condition. Slow changes of more than 3% in SaO2 were carried out in 20 mechanically ventilated neonates by altering the inspired oxygen fraction. For each change the regression lines of TOSc versus SaO2, TOSa versus SaO2 and TOSc versus TOSa were calculatcd. For each infant the mcan slope, intercept and r2 of these lines were determined. In 18 preterm infants we obtained median 9.5 (range one to 13) measurements corresponding to a total of 166 measurements. The mean SaO2 was 91.6 (SD 2.3)%, TOSc was 64.7 (SD 7.2)% and TOSa was 71.4 (SD 11.0)%. Changes in TOSc and TOSa were strongly correlated to changes in SaO2 (r2 = 0.86 and r2 = 0.87). TOSc considerably but systematically underestimated the size of the change: delta TOSc = 0.49 delta SaO2. TOSa quantified changes reasonably correctly: delta TOSa = 0.90 delta SaO2. Changes in TOSc and TOSa were highly correlated (r2 = 0.98). These results are promising, but the large inter-individual variation requires further work.

Algorithms↗

Involvement of oxo-bridged binuclear iron centers in oxygen transport, oxygen reduction, and oxygenation.

The occurrence of an oxo-bridged binuclear iron site is well-established for the oxygen transport protein, hemerythrin, and strongly implicated in ribonucleotide reductase, purple acid phosphatase, ferritin, and methane monooxygenase. Key identifying characteristics are an antiferromagnetic interaction between the two iron atoms, an Fe-O-Fe vibrational mode in the resonance Raman spectrum, and an S = 1/2 EPR signal upon one-electron reduction. In hemerythrin the oxo bridge serves as a hydrogen bond acceptor which stabilizes the bound hydroperoxide. In ribonucleotide reductase both the binuclear iron center and a protein tyrosine undergo oxidation in the presence of molecular oxygen, whereas in methane monooxygenase a binuclear iron moiety may activate O2 for substrate oxygenation.

Iron↗