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Complexities in ETS-domain transcription factor function and regulation: lessons from the TCF (ternary complex factor) subfamily. The Colworth Medal Lecture.

The ETS-domain transcription factor family can be divided into a series of subfamilies. Elk-1 represents the founding member of the ternary complex factor (TCF) subfamily. By focusing on the TCF subfamily, we can demonstrate the complexities that exist in the function and regulation of ETS-domain transcription factors. This article focuses on Elk-1 in detail and summarizes the functions of other TCFs. The key themes covered include the domain structure of the TCFs, the mechanisms of complex formation with serum response factor, regulation of TCFs by mitogen-activated protein kinase cascades, and transcriptional regulatory properties of the TCFs. Finally, the emerging role of the TCFs in vivo is discussed. A picture is developing indicating that, while these proteins exhibit significant sequence and functional conservation, key differences in their structure and regulation are being identified which may relate to unique functions of these proteins in vivo.

Amino Acid Sequence↗

[Determination of heart time volume using the Fick principle in the early postoperative phase after correction of congenital heart defects. Comparison of the calculation of arterio-mixed venous oxygen differences and pulmonary oxygen uptake with the calculation of arterial-central venous oxygen differences and pulmonary oxygen uptake].

UNLABELLED: Comparison of the calculation by means of the arterio-mixed venous oxygen difference and the oxygen uptake with the calculation by means of the arterio-central venous oxygen difference and the oxygen uptake. OBJECTIVE: How reliable is the measurement of cardiac output on Fick's principle without a pulmonary artery catheter? SETTING: PICU in an University hospital. DESIGN: In the postoperative period following complete repair of congenital heart disease we carried out 91 simultaneous measurements of blood gases in 45 infants and children (mean age 18.6 months, mean body weight 8.9 kg) from a systemic artery, the A. pulmonalis, and the V. cava superior. We also determined the pulmonary oxygen uptake in 24 patients (48 measurements). Cardiac output was calculated on Fick's principle using the arterio-mixed venous oxygen difference and the pulmonary oxygen uptake (HZV a-pa) and compared to the cardiac output derived from the central venous values (HZV a-zv). We differentiated between patients with a left to right shunt of 10% or more postoperatively (group A, n = 18) and all others (group B, n = 27). RESULTS: In both groups the correlation coefficient between HZV a-zv and HZV a-pa was high (group A: r = 0.97, group B: r = 0.94). In group A HZV a-pa (mean: 1958 ml/min) was higher than HZV a-zv (mean: 1340 ml/min), group B showed the opposite situation (mean HZV a-pa: 1136 ml/min, mean HZV a-zv: 1373 ml/min). With the Wilcoxon signet-rank test we found significant differences between the partial pressure of oxygen and the saturation of central venous and mixed venous blood samples in both groups, but HZV a-zv and HZV a-pa were different significantly on a level of p < or = 0.01 only in group A. CONCLUSIONS: In both groups HZV a-pa and HZV a-zv correlated well. Therefore, if a pulmonary artery catheter is not inserted; the course of the cardiac output can be calculated with acceptable reliability from the central venous blood gases. By means of Fick's principle the pulmonary blood flow is determined, which is higher than the systemic blood flow in cases of left to right shunting, because of the recirculation in the pulmonary blood circuit. Interpreting the results this has to be taken into account.

Arteries↗

The relationships between arterial oxygen flow rate, oxygen binding by hemoglobin, and oxygen utilization after myocardial infarction.

The interrelationships of arterial oxygen flow rate index, oxygen binding by hemoglobin, and oxygen consumption have been examined in patients with acute myocardial infarction. Proportional extraction of oxygen increased in close association with decreasing oxygen flow rate, and hence, whole body oxygen consumption was constant over nearly a three-fold variation in arterial oxygen flow rate. A reduction in hemoglobin-oxygen affinity at in vivo conditions of pH. Pco(2) and temperature also occurred in proportion to the reduction in arterial oxygen flow rate. Therefore, the increased proportional removal of oxygen from arterial blood at low oxygen flow rates, required to maintain oxygen consumption, may have been facilitated by the reduced affinity of hemoglobin for oxygen at in vivo conditions. However, the decrease in affinity did not appear to explain more than 30-40% of the increased extraction. Respiratory alkalosis was a frequent occurrence in these patients and 2,3-diphosphoglycerate was positively associated with blood pH as well as with the time-averaged proportion of deoxyhemoglobin in arterial and venous blood.Hemoglobin-oxygen affinity measured at standard conditions and the mixed venous oxygen saturation were equally good indicators of reduced arterial oxygen flow rate in patients without shock. However, Svo(2) is more easily measured and is a more useful indicator of reduced oxygen flow rate, since its relationship to oxygen flow appears to be independent of affinity changes and time.

Adult↗

Plasma oxygen during cardiopulmonary bypass: a comparison of blood oxygen levels with oxygen present in plasma lipid.

1. Although not often appreciated, it is a fact that molecular oxygen is more soluble in lipids than in aqueous solution. We have recently developed a method to monitor oxygen within the lipid content of plasma. Monitoring plasma oxygen is one essential element during open heart surgery using a cardiopulmonary bypass pump and oxygenator. Currently oxygen is monitored electrochemically and is based upon monitoring the partial pressure of oxygen in a gas equilibrated with whole blood. 2. To determine the relative importance of lipid-associated oxygen in blood and assess the potential use of such a measurement we present comparisons of changes in oxygen associated with whole blood and lipid content of plasma before, during and after cardiac surgery. 3. In a limited number of patients studied (n = 28), aged between 34 and 86 years, oxygen in lipid increased with decreased extracorporeal blood temperature during cardiopulmonary bypass, increased in proportion to oxygen supplied and appeared to be a better monitor of oxygen than conventional electrochemical systems currently in use. Oxygen associated with whole blood and plasma lipid was markedly below normal on aortic declamping after cardiopulmonary bypass, suggesting an hypoxic episode at this point. Levels of oxygen in the lipid phase of plasma returned to normal presurgical values 6-8 h after surgery. 4. Calculation of the concentration of lipid-associated oxygen present in plasma suggests that plasma lipids contain up to 25% of that typically ascribed to haemoglobin. Thus, we suggest that monitoring lipid-associated oxygen may prove a better alternative to current methods of measuring oxygen status. Furthermore, we suggest that plasma lipid is a hitherto unsuspected pool of circulating oxygen which may play a significant role in tissue oxygen supply.

Adult↗

The oxygen status of the arterial blood revised: relevant oxygen parameters for monitoring the arterial oxygen availability.

The new generation of very accurate multi-wavelength oximeters, e.g. OSM3, for in vitro measurement of the hemoglobin oxygen saturation, total hemoglobin concentration, and carboxy- and methemoglobin fractions opens new aspects of oxygen monitoring. Combined with the data from the blood gas analyzer (e.g. ABL300) these very accurate measurements allow the calculation of several derived oxygen parameters on the basis of a set of newly developed calculation algorithms. The traditional parameters obtained from an arterial sample are the oxygen tension (pO2) and the hemoglobin oxygen saturation (sO2). Clinical examples illustrate that the pO2 and the sO2 even in combination may give misleading information. The new algorithm calculates three extra oxygen parameters. 1) The oxygen extraction tension, px, defined as the tension required to extract 2.3 mmol of oxygen per liter blood. It signals the mixed venous pO2 level on the assumption that the arterio-venous oxygen difference is normal (2.3 mmol/L). 2) The concentration of extractable oxygen, cx, defined as the concentration of oxygen extracted at a tension of 5.0 kPa. 3) The oxygen compensation factor, Qx, derived as (2.3 mmol/L)/cx. It may be interpreted as the increase in cardiac output necessary to maintain a normal mixed venous pO2 of 5 kPa. These three parameters indicate the oxygen availability of the blood and summarize important properties of the arterial blood in relation to oxygen supply of the tissues, including the arterial pO2, the 'active' hemoglobin concentration (equivalent to the oxygen capacity), and the hemoglobin oxygen affinity (p50). The set of data measured with the blood gas analyzer, e.g. the ABL300 combined with the data measured with the OSM3 contains much more information than is routinely utilized. This information is extracted and summarized by our calculation algorithm. Omitting the calculation of the extra oxygen parameters involves a risk of losing valuable information.

Arteries↗

[Oxygen status of arterial blood including uncompensated mixed venous oxygen tension and cardial oxygen compensation factor. Reevaluation on the basis of 250 arterial punctures].

In arterial blood from 250 patients we measured pH, pco2, and po2 (electrochemically) together with total-hemoglobin concentration, oxygen saturation, carboxy- and methemoglobin fractions (spectrometrically). With a previously published algorithm we calculated the effective hemoglobin concentration, total-oxygen concentration, half saturation tension, erythrocyte 2,3-diphosphoglycerate concentration, and two new oxygen parameters: uncompensated mixed venous oxygen tension and cardiac oxygen compensation factor. 11% of the patients have normal arterial oxygen tension, but nevertheless risk of tissue hypoxia judged from the two new oxygen parameters. This is due to a low hemoglobin concentration and/or low half saturation tension (increased hemoglobin oxygen affinity). Some patients have decreased arterial oxygen tension but normal uncompensated mixed venous oxygen tension (15%) or normal cardiac oxygen compensation factor (9%). This is due to a high hemoglobin concentration and/or increased half saturation tension. The latter varies from 2.6 to 5.2 kPa (ref.: 3.3-3.9 kPa); 36% have decreased, 27% increased values. The 2,3-diphospho-glycerate concentration varies from 2.0 to 7.9 mmol/l (ref.: 3.6-5.1 mmol/l); 14% have decreased, 30% increased values. Uncompensated mixed venous oxygen tension varies from 1.8 to 5.7 kPa (ref.: 4.5-5.5 kPaf). The cardiac oxygen compensation factor varies from 0.9 to infinity (ref.: 0.8-1.6). We conclude that the variation in the different oxygen parameters is so significant that it justifies routine calculation for all arterial blood samples where the measurement on a conventional blood gas analyzer is supplemented with measurement on one of the new multi-wavelength hemoximeters. The calculation algorithm permits calculation of all the oxygen parameters for the majority of arterial samples (84%) where the oxygen saturation is less than or equal to 0.970.

Adult↗

Oxygen transport and oxygen consumption during supplemental oxygen administration in patients with chronic obstructive pulmonary disease.

PURPOSE: Oxygen consumption (VO2) is independent of oxygen delivery (DO2) above a critical level of DO2. VO2 may become dependent on DO2 when oxygen demand exceeds oxygen supply. We studied DO2 VO2, and exercise capacity in 12 stable, ambulatory patients with chronic obstructive pulmonary disease (COPD) receiving ambient air and 26% oxygen to ascertain whether VO2 is dependent on DO2 in this patient sample. PATIENTS AND METHODS: An exercise protocol consisting of a symptom-limited, low-level treadmill test with progressive increments in workload was performed twice, once with patients breathing ambient air and once with patients breathing 26% oxygen. Expired gas, arterial and mixed venous blood values, and recordings of systemic and pulmonary artery pressures were obtained after a 10-minute period of rest (while standing) and during the last minute of each three-minute exercise level. RESULTS: Five patients had an increase in exercise capacity, defined as an increase in the maximal VO2 greater than 25%, using supplemental oxygen. In these patients, oxygen delivery increased from 10.9 +/- 3.4 to 13.8 +/- 4.7 mL/minute/kg (p = 0.008) at rest and from 16.2 +/- 5.0 to 24.7 +/- 2.7 mL/minute/kg (p = 0.046) during exercise with supplemental oxygen administration. VO2 increased from 0.329 +/- 0.065 to 0.436 +/- 0.109 L/minute (p = 0.029) at rest and from 0.776 +/- 0.275 to 1.119 +/- 0.482 L/minute (p = 0.048) during exercise. Three of these five patients had an arterial oxygen pressure greater than 55 mm Hg at rest. Seven patients had little or no increase in exercise capacity with supplemental oxygen. This patient group had no increase in VO2 at rest. The DO2 failed to increase at rest despite an increase in arterial oxygen content because of a reduction in cardiac output. CONCLUSION: These data demonstrate that DO2 may fail to increase in some patients with COPD and resting or exertional hypoxemia when supplemental oxygen is administered because of a reduction in cardiac output; that patients who fail to increase their DO2 are less likely to increase exercise capacity; and that some stable, ambulatory patients with COPD who do not qualify for supplemental oxygen at rest by current standards may have inadequate DO2 to meet physiologic needs.

Aged↗

Oxygen delivery during endobronchial anaesthesia: a comparison of halothane-oxygen and nitrous oxide-oxygen.

Total oxygen delivery (cardiac output X arterial oxygen content) and oxygen consumption were determined in 22 patients undergoing one-lung ventilation (OLV) during thoracotomy. In 11 patients, anaesthesia was maintained with halothane-oxygen and in another 11 patients with nitrous oxide-oxygen-analgesic combination (FIO2 0.5). During OLV, oxygen delivery was greater in the halothane group and these patients tended to show a decrease in oxygen consumption compared with the patients of the nitrous oxide group. Therefore, as far as total oxygen balance (oxygen delivery/oxygen consumption) during OLV is concerned, halothane-oxygen maintenance provides a greater margin of safety than nitrous oxide-oxygen-analgesic combination. However, in spite of occasional hypoxaemic episodes, none of our patients receiving 50% nitrous oxide in oxygen showed an oxygen delivery coefficient (oxygen delivery/oxygen consumption) significantly smaller than the predicted normal value for an unanaesthetized patient. This finding may explain why this anaesthetic technique has been used without apparent harm during OLV in patients with unimpaired cardiovascular function.

Anesthesia↗

Effect of the arterial oxygenation level on cardiac output, oxygen extraction, and oxygen consumption in low birth weight infants receiving mechanical ventilation.

OBJECTIVE: To investigate the effects on oxygenation of targeting the higher versus the lower end of the currently recommended range for pulse oximetry (Spo2). DESIGN: Nonrandomized crossover trial with the use of within-subject comparisons (two-tailed paired t test). SETTING: Level III neonatal intensive care unit of a university hospital. PATIENTS: Twenty infants whose lungs were mechanically ventilated (mean +/- SD: birth weight, 1192 +/- 396 gm; gestational age, 28.7 +/- 2.7 weeks; age at time of study, 42 +/- 26 hours). INTERVENTIONS: The inspired oxygen concentration was adjusted to achieve Spo2 readings of 93% to 96% versus 89% to 92% (Ohmeda pulse oximeter) or 95% to 98% versus 91% to 94% (Nellcor oximeter). MEASUREMENTS: Cardiac output was measured by echocardiography, oxygen content of arterial blood samples by cooximetry, and oxygen consumption by indirect calorimetry. RESULTS: The inspired oxygen concentrations required to achieve the Spo2 target ranges were 39.8% +/- 8.3% versus 28.7% +/- 6.1% (p < 0.001). The respective arterial oxygen contents were 18.0 +/- 2.6 ml/dl versus 16.9 +/- 2.5 ml/dl (p < 0.001). Oxygen consumption was unchanged. In the lower-oxygen condition no compensatory increase in cardiac output was detected; thus the estimated mixed venous oxygen tension decreased and the oxygen extraction ratio increased. Venous admixture increased from 15% +/- 6% to 31% +/- 9% in the lower-oxygen condition (p < 0.001). CONCLUSIONS: The "low normal" Spo2 target range allowed for less oxygen exposure. No signs of mismatch between systemic oxygen delivery and demand could be detected.

Blood Gas Analysis↗

Comparison of the efficacy of a demand oxygen delivery system with continuous low flow oxygen in subjects with stable COPD and severe oxygen desaturation on walking.

BACKGROUND: Provision of ambulatory oxygen using an intermittent pulsed flow regulated by a demand oxygen delivery system (DODS) greatly increases the limited supply time of standard portable gaseous cylinders. The efficacy of such a system has not previously been studied during submaximal exercise in subjects with severe chronic obstructive pulmonary disease (COPD) in whom desaturation is likely to be great and where usage is often most appropriate. METHODS: Fifteen subjects with severe COPD and oxygen desaturation underwent six minute walk tests performed in random order to compare the efficacy of a demand oxygen delivery system (DODS) with continuous flow oxygen. Walk distance, breathlessness, oxygen saturation, resting time, and recovery time (objective and subjective) were recorded and compared for each walk. RESULTS: Breathing continuous oxygen compared with baseline air breathing improved mean walk distance (295 m versus 271 m) and recovery time (47 seconds versus 112 seconds), whilst the lowest recorded saturation (81% versus 74%) and time desaturated below 90% (201 seconds versus 299 seconds) were reduced. When the DODS was compared with air breathing only the walk distance changed (283 m versus 271 m). A comparison of the DODS with continuous oxygen breathing showed the DODS to be less effective at oxygenating subjects with inferior lowest saturation (78% versus 81%), time spent below 90% (284 seconds versus 201 seconds), time to objective recovery (83 seconds versus 47 seconds), and walk distance (283 m versus 295 m). CONCLUSIONS: Neither of the delivery systems was able to prevent desaturation in these subjects. The use of continuous flow oxygen, however, was accompanied by improvements in oxygenation, walk distance, and recovery time compared with air breathing. The DODS produced only a small increase in walk distance without elevation of oxygen saturation, but was inferior to continuous flow oxygen in most of the measured variables when compared directly.

Administration, Inhalation↗

Arterial oxygenation and oxygen delivery after hemoglobin-based oxygen carrier infusion in canine hypovolemic shock: a dose-response study.

OBJECTIVE: To compare effects of 6% hetastarch (Hextend) and hemoglobin-based oxygen carrier hemoglobin glutamer-200 (Hb-200) (bovine; Oxyglobin) on hemodynamics, arterial oxygen content, and systemic oxygen delivery in a canine hemorrhagic shock model. DESIGN: Randomized laboratory investigation. SETTING: University surgical research facility. SUBJECTS: Twenty-four anesthetized healthy, adult, mongrel dogs (28 +/- 1 kg; 7 female, 17 male). INTERVENTIONS: Dogs were instrumented for determinations of heart rate, arterial, central venous, pulmonary arterial, and pulmonary arterial occlusion pressures, and cardiac index. Total solids, colloid oncotic pressure, arterial oxygen content, Hb, lactate, pH, and blood gases were analyzed in blood samples. Recordings were made before, after 1 hr of hemorrhagic shock, and immediately and 3 hrs after infusion of either 30 mL/kg hetastarch (group 1), 10 mL/kg Hb-200 + 20 mL/kg hetastarch (group 2), 20 mL/kg Hb-200 + 10 mL/kg hetastarch (group 3), or 30 mL/kg Hb-200 (group 4). MEASUREMENTS AND MAIN RESULTS: Hemorrhage (35 +/- 1 mL/kg) reduced mean arterial pressure to 50 mm Hg and caused significant decreases in total Hb, mean pulmonary arterial pressure, cardiac index and systemic oxygen delivery, increases in heart rate and systemic vascular resistance, and lactic acidosis. In group 1, hetastarch infusion was accompanied by increases of pulmonary arterial pressure, cardiac index, and blood oxygen extraction above baseline, and decreases of systemic vascular resistance, total Hb, total solids, arterial oxygen content, and systemic oxygen delivery below baseline (p <.05). Other data returned to baseline. In groups 2 to 4, hemodynamic functions (except pulmonary arterial pressure) recovered, yet neither total Hb (i.e., plasma and red blood cell Hb) nor arterial oxygen content increased despite increases in plasma Hb of 2 to 5 g/dL and proportionate increases in total solids. Systemic oxygen delivery improved dose-dependently with Hb-200 but did not return to baseline (p <.05), reaching values comparable to hetastarch group only at 30 mL/kg Hb-200. In all groups, oxygen extraction remained above baseline. Metabolic acidosis and lactatemia resolved significantly faster in groups 2 to 4, and colloid oncotic pressure after resuscitation was greater in groups 2 to 4 than in controls (p <.05). CONCLUSIONS: In hemorrhagic shock, Hb-200 infusion may not improve oxygen delivery more than hetastarch, likely due to hemodilution caused by its high colloid oncotic pressure, but may facilitate diffusive oxygen transport to tissues.

Analysis of Variance↗

Investigation of the human oxygen transport system during conditions of rest and increased oxygen consumption by means of fractionation. Effects of oxygen isotopes.

The aim of the study was to assess various pathways of the oxygen transport system at rest and ergometer work by the utility of information derivable from different behaviour of the isotopic oxygen molecules 16O2 and 16O18O during transport. 6 healthy humans were studied at rest and at different levels of ergometer work, ranging from 50 to 250 W. Isotope analysis was performed by applying a reference technique. Samples of inspiratory and expiratory gas, taken during steady state conditions, were analysed by a respiratory mass spectrometer on their 16O18O/16O2 ratios by comparing them with a reference gas of appropriate composition. Ventilatory minute volume, oxygen consumption and end-expiratory oxygen partial pressure were also measured. At rest, the delta IU-value quantifying the isotope effect of the overall oxygen transport amounted to 0.74 +/- 0.08%. During ergometer work, the fractionation factor steadily decreased with increasing oxygen consumption, yielding the regression line delta IU [%] = 0.74 -1.3.10(-4).VO2, where VO2 is oxygen consumption given in ml/min. With respect to oxygen transport from inspiratory gas to tissue, this result suggests: convective processes of oxygen transport become more limiting with increasing oxygen consumption, whereas diffusion does not become a major limiting step up to oxygen consumption rates of 3600 ml/min, otherwise a reverse relationship between fractionation factor and oxygen consumption should have been found.

Biological Transport, Active↗

Measuring brain tissue oxygenation compared with jugular venous oxygen saturation for monitoring cerebral oxygenation after traumatic brain injury.

UNLABELLED: Jugular bulb oximetry is the most widely used method of monitoring cerebral oxygenation. More recently, measurement of brain tissue oxygenation has been reported in head-injured patients. We compared the changes in brain tissue oxygen partial pressure (PbO2) with changes in jugular venous oxygen saturation (SjVO2) in response to hyperventilation in areas of brain with and without focal pathology. Thirteen patients with severe head injuries were studied. A multiparameter sensor was inserted into areas of brain with focal pathology in five patients and outside areas of focal pathology in eight patients. A fiberoptic catheter was inserted into the right jugular bulb. Patients were hyperventilated in a stepwise manner from a PaCO2 of approximately 35 mm Hg to a PaCO2 of 22 mm Hg. There was no significant change in cerebral perfusion pressure or arterial partial pressure of oxygen with hyperventilation. In areas without focal pathology, there was a good correlation between changes in SjVO2 and PbO2 (deltaSjVO2 and deltaPbO2; r2 = 0.69, P < 0.0001). In areas with focal pathology, there was no correlation between deltaSjVO, and APbO2 (r2 =0.07, P = 0.23). In this study, we demonstrated that measurement of local tissue oxygenation can highlight focal differences in regional cerebral oxygenation that are disguised when measuring SjVO2. Thus, monitoring of PbO2 is a useful addition to multimodal monitoring of patients with traumatic head injury. IMPLICATIONS: Brain oxygenation is currently monitored by using jugular bulb oximetry, which attracts a number of potential artifacts and may not reflect regional changes in oxygenation. We compared this method with measurement of brain tissue oxygenation using a multiparameter sensor inserted into brain tissue. The brain tissue monitor seemed to reflect regional brain oxygenation better than jugular bulb oximetry.

Adult↗

Oxygen carrying capacity and oxygen supply rate of artificial oxygen carrier, Neo Red Cell (NRC).

Neo Red Cell (NRC), which is the liposome encapsulated hemolysate, has been developed as an artificial oxygen carrier. Oxygen carrying capacity and oxygen supply rate of NRC were estimated by continuous measurement of dissolved oxygen concentration in a spinner vessel. Oxygen carrying capacity of the medium was risen by adding NRC. The oxygen supply rate of the NRC medium containing hepatocytes was determined by the oxygen consumption rate of hepatocytes. The addition of NRC gave no effect on the oxygen transfer rate from gas phase to liquid phase (or kL a value) of the solution in the spinner vessel. The rate of oxygen absorption to NRC was limited by the oxygen transfer rate from gas phase to liquid phase in the spinner vessel. These results indicate that the oxygen supply from NRC may sustain the high-density culture of mammalian cells.

Air↗

Intraoperative fetal oxygen saturation during Caesarean section: general anaesthesia using sevoflurane with either 100% oxygen or 50% nitrous oxide in oxygen.

BACKGROUND AND OBJECTIVE: The study was designed to evaluate whether the administration of sevoflurane in 100% oxygen for anaesthesia during Caesarean section would improve fetal and neonatal oxygenation compared with the administration of sevoflurane with 50% nitrous oxide in oxygen. METHODS: The randomized, single-blind controlled study examined 24 mothers, ASA I-II, at term undergoing Caesarean section who were allocated to receive sevoflurane in either 100% oxygen (n = 13) or 50% nitrous oxide in oxygen (n= 11). General anaesthesia was induced in both groups with thiopental 4-5 mg kg(-1) followed by succinylcholine 1.5 mg kg(-1) to facilitate tracheal intubation. Parturients received sevoflurane given either in 100% O2 or in a 50:50 nitrous oxide and oxygen mixture, using 0.5-1.0% progressive incremental dosing up to 1.5-2.0 MAC. Non-invasive fetal oxygen saturation was measured between induction to delivery, and umbilical artery and vein PaO2 were evaluated at birth. RESULTS: Intraoperative fetal oxygen saturation increased in all patients after maternal 100% oxygen administration (P < 0.01). Maternal hyperoxygenation significantly increased the umbilical vein and umbilical artery PaO2 and the umbilical artery SaO2 at birth (P < 0.0001). CONCLUSIONS: Maternal hyperoxygenation significantly improves fetal as well as neonatal oxygenation.

Adult↗

Biphasic oxygen kinetics of cellular respiration and linear oxygen dependence of antimycin A inhibited oxygen consumption.

Oxygen kinetics in fibroblasts was biphasic. This was quantitatively explained by a major mitochondrial hyperbolic component in the low-oxygen range and a linear increase of rotenone- and antimycin A-inhibited oxygen consumption in the high-oxygen range. This suggests an increased production of reactive oxygen species and oxidative stress at elevated, air-level oxygen concentrations. The high oxygen affinity of mitochondrial respiration provides the basis for the maintenance of a high aerobic scope at physiological low-oxygen levels, whereas further pronounced depression of oxygen pressure induces energetic stress under hypoxia.

Antimycin A↗

The derivation of the formyl-group oxygen of chlorophyll b in higher plants from molecular oxygen. Achievement of high enrichment of the 7-formyl-group oxygen from 18O2 in greening maize leaves.

The mechanism of formation of the formyl group of chlorophyll b has long been obscure but, in this paper, the origin of the 7-formyl-group oxygen of chlorophyll b in higher plants was determined by greening etiolated maize leaves, excised from dark-grown plants, by illumination under white light in the presence of either H2(18)O or 18O2 and examining the newly synthesized chlorophylls by mass spectroscopy. To minimize the possible loss of 18O label from the 7-formyl substituent by reversible formation of chlorophyll b-7(1)-gem-diol (hydrate) with unlabelled water in the cell, the formyl group was reduced to a hydroxymethyl group during extraction with methanol containing NaBH4: chlorophyll a remained unchanged during this rapid reductive extraction process. Mass spectra of chlorophyll a and [7-hydroxymethyl]-chlorophyll b extracted from leaves greened in the presence of either H2(18)O or 18O2 revealed that 18O was incorporated only from molecular oxygen but into both chlorophylls: the mass spectra were consistent with molecular oxygen providing an oxygen atom not only for incorporation into the 7-formyl group of chlorophyll b but also for the well-documented incorporation into the 13(1)-oxo group of both chlorophylls a and b [see Walker, C. J., Mansfield, K. E., Smith, K. M. & Castelfranco, P. A. (1989) Biochem. J. 257, 599-602]. The incorporation of isotope led to as much as 77% enrichment of the 13(1)-oxo group of chlorophyll a: assuming identical incorporation into the 13(1) oxygen of chlorophyll b, then enrichment of the 7-formyl oxygen was as much as 93%. Isotope dilution by re-incorporation of photosynthetically produced oxygen from unlabelled water was negligible as shown by a greening experiment in the presence of 3-(3,4-dichlorophenyl)-1,1-dimethylurea. The high enrichment using 18O2, and the absence of labelling by H2(18)O, unequivocally demonstrates that molecular oxygen is the sole precursor of the 7-formyl oxygen of chlorophyll b in higher plants and strongly suggests a single pathway for the formation of the chlorophyll b formyl group involving the participation of an oxygenase-type enzyme.

Chlorophyll↗

Molecular oxygen: friend and foe. The role of the oxygen free radical system in the calcium paradox, the oxygen paradox and ischemia/reperfusion injury.

We strongly support the original intriguing hypothesis of Hearse et al. that the oxygen paradox and the calcium paradox are facets of the same problem. We would propose that the major similarity is a final common pathway leading to intracellular calcium overload and the sequelae of the resultant increase in intracellular calcium. In addition, we would propose that the oxygen paradox and ischemic/reperfusion injury are also facets of the same problem with the major similarity being the reintroduction of molecular oxygen to a previously hypoxic myocardium. Finally, we would suggest that the common pathway leading to intracellular calcium overload in the oxygen paradox and ischemic/reperfusion injury and to a lesser extent the calcium paradox involves the generation of oxygen free radicals. The source of oxygen free radical generation in the calcium paradox is perhaps less obvious than in the oxygen paradox. It is proposed that during calcium-free perfusion, calcium is leached from the plasmalemma of the myocyte. There is a resulting increase in membrane fluidity. Within the plasmalemma are a number of calcium sensitive phospholipases. Upon reperfusion with a calcium replete medium, calcium could pool around these membrane bound phospholipases initiating a chain reaction of lipid peroxidation which actually is perpetuated by free radical generation (Equations 5A-5C). Lipid peroxidation opens channels within the plasmalemma rendering a 'leaky' sarcolemma. It is through these channels that calcium could flow down its concentration gradient into the cell. The increased calcium accumulation at the mitochondria would lead to an uncoupling of oxidative phosphorylation. With depleted energy stores, the mitochondria and sarcoplasmic reticulum no longer serve as calcium sinks. This would contribute to the calcium overload seen upon reperfusion. The role of oxygen free radical production would appear to occur during the hypoxic phase of the oxygen paradox and the ischemic phase of ischemic/reperfusion injury and during the reoxygenation/reperfusion phases. With the onset of hypoxia and/or myocardial ischemia there is an increase in reducing equivalents, disturbance and dissociation of intramitochondrial electron transport and release of ubisemiquinone, flavoproteins and superoxide radicals. The increase in reducing equivalents includes NADPH and, in ischemia, catecholamines, hypoxanthine and an increase on xanthine oxidase activity. All of these substrates are capable of participating in free radical production. This increase in free radical production in ischemic tissue is enhanced by acidosis which in the ischemic and hypoxic myocardium approaches pH 6.0-6.4.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗