Higher Oxygen Saturation Research Articles

Treatment of selected patients with an ununited fracture of the proximal part of the scaphoid by excision of the fragment and insertion of a carved silicone rubber spacer.

Management of cervical spine injuries in polytrauma patients involves a comprehensive assessment that consists of a physical examination and imaging studies to identify substantial injury. The management of diagnosed cervical spine injuries in polytrauma patients should be coordinated with the management of other injuries. Timely management is required in polytrauma patients with a spinal cord injury. A high oxygen saturation level must be maintained and a mean arterial blood pressure of 85 mm Hg is recommended. Reduction via traction or urgent surgical decompression, as indicated, should be considered. Reduction that is performed within a few hours postinjury may reverse neurologic deficits, and decompression that is performed within 24 hours postinjury increases the likelihood of substantial recovery. Neuroprotection with the use of methylprednisolone is not recommended in polytrauma patients with a cervical spine injury. Early surgical treatment is safe in polytrauma patients with a cervical spine injury who are adequately resuscitated. The surgical approach is directed by the fracture type and the requirements for decompression. Anterior surgical approaches are preferred in polytrauma patients with a cervical spine injury, and definitive surgical treatment may be delayed.

The Klippel-Trenaunay syndrome with acro-angiodermatitis (pseudo-Kaposi´s sarcoma)

A patient with the Klippel-Trenaunay syndrome and pseudo-Kaposi elements is reported. This combination of symptoms has only been published very occasionally. Selective quantitative measurements of the peripheral tissue blood flow revealed a significantly increased cutaneous blood flow in the hypertrophied leg. This finding supports the assumption that a high perfusion rate and a high oxygen saturation are involved in the etiopathogenesis of the pseudo-Kaposi elements.

Changes of hepatic function after hepatic artery ligation.

In our series of 12 patients with unresectable primary liver cancers, hepatic function changes after hepatic artery ligation (HAL) have been investigated. Significant elevation of SGPT, SGOT and LDH were observed on the one hand, and only slight or no derangement in AKP, γ-GT, 5’-NT and bilirubin was noted on the other hand. Factors influencing hepatic function changes after HAL are discussed. The importance of high postoperative oxygen saturation of portal vein blood in maintaining a stable oxygen consumption of hepatocytes is stressed.

Intracellular polymerization of sickle hemoglobin. Effects of cell heterogeneity.

To determine the extent to which the broad distribution in intracellular hemoglobin concentrations found in sickle erythrocytes affects the extent of intracellular polymerization of hemoglobin S, we have fractionated these cells by density using discontinuous Stractan gradients. The amount of polymer formed in the subpopulations was experimentally measured as a function of oxygen saturation using 13C nuclear magnetic resonance spectroscopy. The results for each subpopulation are in very good agreement with the theoretical predictions based on the current thermodynamic description for hemoglobin S gelation. We further demonstrate that the erythrocyte density profile for a single individual with sickle cell anemia can be used with the theory to predict the amount of polymer in unfractionated cells. We find that heterogeneity in intracellular hemoglobin concentration causes the critical oxygen saturation for formation of polymer to shift from 84 to greater than 90%; polymer is formed predominantly in the dense cells at the very high oxygen saturation values. The existence of polymer at arterial oxygen saturation values has significance for understanding the pathophysiology of sickle cell anemia. The utility of these techniques for assessing various therapeutic strategies is discussed.

8-Bromo cyclic GMP inhibits NADH and lactate accumulation in hypoxic rat atria.

The effects of 8-bromo-cGMP on tissue lactate and NADH levels were studied under conditions of high oxygen saturation (95-100%) and hypoxia (50%) in spontaneously beating rat atria. The induction of hypoxia caused a rapid decline in contractility with a simultaneous increase in tissue lactate and NADH. 8-bromo-cGMP (10(-4) mol/l) prevented the accumulation of lactate occurring during hypoxia. It also lowered the level of lactate during high oxygen saturation. Furthermore, 8-bromo-cGMP inhibited the hypoxia-induced increase in NADH and lowered the level of NADH in high oxygen saturation. 8-bromo-cGMP did not affect contractility or heart rate during hypoxia. It is concluded that cGMP may influence the redox-state and metabolism in a direction which is beneficial for the hypoxic myocyte. It is also suggested that antianginal nitro compounds which enhance the level of cGMP might exert an effect similar to that of 8-bromo-cGMP.

Sodium nitroprusside inhibits lactate formation in rat atria: is cyclic GMP involved?

Sodium nitroprusside (NP) was found to decrease the tissue lactate level under conditions of high (HiOxSa) and low (hypoxia) oxygen saturation in spontaneously beating rat atria. Nitroprusside also increased the level of cyclic GMP (cGMP) in a dose-dependent manner in both states. The time course and dose dependence of these effects suggest that cGMP might be responsible for the decreased tissue level of lactate demonstrated. The findings suggest that cGMP might inhibit lactate production in HiOxSa and antagonize the hypoxia-induced acceleration of anaerobic metabolism. It is proposed that a state of low-rate glycolysis results from this inhibitory effect of cGMP. Furthermore, the possible role of cGMP as a feed-back regulator of the redox state is discussed in the light of these findings.

Regulation of cardiac contractility and glycolysis by cyclic nucleotides during hypoxia.

It has been suggested that cyclic nucleotides (cAMP and cGMP) participate in the regulation of cardiac contractility and glycolysis. In the present study, this possible involvement was examined in spontaneously beating rat atria during hypoxia (50% oxygen saturation). Thirty seconds after reduction of high oxygen saturation (HiOxSa) in the incubation medium, the contraction amplitude declined to 50% of the initial level. The decline was partly antagonized by norepinephrine (NE) or hypercalcemia. The cAMP level remained unchanged during hypoxia, but the cGMP content gradually increased. Paradoxically, the production of lactate decreased after 30 sec of hypoxia but had increased by 2 min, when depletion of creatine phosphate and ATP stores was also initiated. Sodium nitroprusside (nitroprusside) and NE elevated the cGMP and cAMP, respectively, in both HiOxSa and hypoxia. Nitroprusside and NE also showed a positive inotropic effect in HiOxSa. Verapamil decreased contractility without changing the levels of cAMP or cGMP. In HiOxSa, both nitroprusside and verapamil decreased lactate production but were not able to resist the increase in atrial lactate level brought about by NE. In hypercalcemia the amplitude increased, but lactate production was slightly reduced in HiOxSa. Between 5 and 10 min of hypoxia, 45Ca uptake was reduced to about one-third of that in the control. It is suggested that lack of oxygen has direct and parallel effects on the sarcolemma and the mitochondria. The former induces deterioration of contractility, the latter termination of aerobic energy production. Cyclic nucleotides are not involved in either of these phenomena. However, at a low rate of anaerobic glycolysis, e.g., in HiOxSa or at the very early stage of hypoxia, cGMP could inhibit and cAMP accelerate lactate production.

The Intracellular Polymerization of Sickle Hemoglobin and Its Relevance to Sickle Cell Disease

In the last few years, the understanding of the molecular basis of sickle cell disease has progressed rapidly. It is now possible to describe the structure of the gel of polymerized deoxyhemoglobin S at molecular and atomic levels and to begin to understand the mechanism of formation of this gel from hemoglobin solutions. There are several current hypotheses for the pathophysiology of this disease based on molecular as well as cellular studies. Recently, it has become possible to measure the amounts of polymerized hemoglobin within erythrocyte populations and thereby demonstrate the existence of polymer in cells at very high oxygen saturation values. This unexpectedly low solubility of deoxyhemoglobin S in sickle erythrocytes can be largely accounted for by the theory of protein nonideality, with some contribution from cell heterogeneity. These results show that hemoglobin S in the erythrocyte behaves as it does in very concentrated hemoglobin solutions. There are strong indications, for both SS and AS cells, of the existence of cells with significant amounts of polymerized deoxyhemoglobin S but without morphological deformation (sickling). On the basis of these and other results, two models relating these biophysical findings to pathophysiology are discussed. First, it is likely that with deoxygenation there is a continuum of cellular changes. Initially, small amounts of polymer form; only with severe and prolonged deoxygenation do large domains of highly ordered, polymerized hemoglobin form in the erythrocyte and cause it to sickle. Second, we combine this model of cellular changes with information from rheologic studies to suggest an alternate model for the pathophysiology of the disease. We postulate that flexibility, governed by the amount and alignment of intracellular polymer, is the principal determinant of the flow of sickle erythrocytes. While cells that have large amounts of ordered polymer may be caught in the capillaries and venules, some cells at relatively high oxygen saturation, with polymer but no deformation, may have difficulty traversing the constriction of the precapillary arterioles. The implications of these recent molecular and cellular studies, as well as of the several models, for the therapy of sickle cell disease are discussed. In general, our analysis suggests that a therapeutically effective strategy is feasible and that certain approaches seem particularly propitious.

On the role of cyclic nucleotides in the regulation of cardiac contractility and glycolysis during hypoxia.

A possible involvement of cyclic nucleotides (cAMP and cGMP) in the regulation of cardiac contractility and glycolysis during hypoxia was examined in spontaneously beating rat atria. A reduction of the high oxygen saturation (HiOxSa) of the incubation medium from 95-100% to half produced a rapid decline of the amplitude. The deterioration of 50% was seen after 30 sec. of hypoxia. The decline was partly antagonized by noradrenaline (NA, 1 X 10(-6) M) or hypercalcaemia (5.7 X 10(-3) M instead of 1.9 X 10(-3) M). The cAMP level remained unchanged during the first 12 min. of hypoxia, but the cGMP content increased gradually and reached a significantly increased level in 4-8 min. Paradoxically, the production of lactate decreased, after 30 sec. of hypoxia, but accelerated then 2-4 min. after the onset of hypoxia. The depletion of creatine phosphate and ATP stores was initiated after 2 min. of hypoxia. The arterial content of the active forms of phosphofructokinase and lactate dehydrogenase gradually rose during hypoxia. Sodium nitroprusside (SNP, 1 X 10(-4) M) and NA produced increases in cGMP and cAMP levels, respectively, both in HiOxSa and hypoxia. SNP induced a slight and NA a marked increase in the amplitude in HiOxSa. Verapamil (1 X 10(-6) M) decreased the contractility, but did not affect the levels of cAMP and cGMP. Both SNP and verapamil decreased the lactate production, but they could not resist the NA-induced increase in the atrial lactate level. Hypercalcaemia increased the amplitude but slightly reduced the lactate production in HiOxSa. 45Ca-uptake was reduced to about 35 per cent of control as measured between 5 and 10 min. of hypoxia. It is concluded that the lack of oxygen could have direct and parallel effects on the sarcolemma and on the mitochondria. The former could result in the deterioration of contractility and the latter in the termination of aerobic energy production. Cyclic nucleotides are not involved in either of these phenomena. However, at the low rate of anaerobic glycolysis, e.g. in HiOxSa or at the very early stage of hypoxia, cGMP could inhibit and cAMP accelerate the lactate production.

A comparison of carbon dioxide production and oxygen uptake in sediment cores from four south Swedish lakes

Carbon dioxide production and oxygen uptake were measured in undisturbed sediment cores taken during winter from four lakes of different trophic state. Respiration was measured at 5, 10, 15 and 20°C at high oxygen saturation (75–100%). The respiratory quotient, calculated from the mean values of carbon dioxide production and oxygen uptake at each temperature for each lake, was 0.83–0.96 with a mean value for the four lakes of 0.90. At very low oxygen saturations (<10%) carbon dioxide production was 21–42% of the production at 20°C and high oxygen saturations. The results indicate that under aerobic conditions, oxygen uptake and carbon dioxide production are closely‐coupled processes in these lake sediments.

Kinetic control of co-operativity in the oxygen binding of Panulirus interruptus hemocyanin

The kinetics of the oxygen reaction of Panulirus interruptus hemocyanin have been studied at pH 9.6 under conditions where the protein exists in the undissociated, co-operative state and in the dissociated, non-co-operative state. Temperature-jump relaxation measurements of the undissociated protein at high oxygen saturation levels show one relaxation process which has been assigned to the high oxygen affinity (R) state, the on and off kinetic constants being 3.1 × 10 7 m −1 s −1 and 60 s −1, respectively. Stopped-flow measurements of the oxygen dissociation reaction show (1) an autocatalytic time-course of the reaction at pH 9.6 and (2) an increase in the overall oxygen dissociation rate constant, as the pH is decreased from 9.6 to 7.0. Temperature-jump relaxation measurements of the dissociated protein show one relaxation process characterized by a very high oxygen dissociation rate constant (1500 s −1) and a combination constant which is of the same order of magnitude as reported for undissociated protein ( k on = 4.6 × 10 7 m −1 s −1 ). The behaviour of dissociated protein can be considered as characteristic of the low oxygen affinity (T) state. The results presented in this paper, together with data available for other hemocyanins as well as hemoglobins, lead to the conclusion that respiratory proteins show a common feature in the kinetic control of co-operative oxygen binding: the stability of the oxygen-protein complex is largely determined by the value of the dissociation rate constant, the oxygen combination process very often appearing to be diffusion controlled.

Atresia of right pulmonary veins and anomalous left pulmonary venous drainage into portal circulation.

<b>Šamánek, M., Tůma, S., Benešová, D., Povýšilová, V., Pražský, F., and Čápová, E. (1974).</b><i>Thorax</i>, <b>29</b>, 446-450. <b>Atresia of right pulmonary veins and anomalous left pulmonary venous drainage into portal circulation.</b> An anomaly of pulmonary venous drainage in a male newborn infant is described whereby the left pulmonary veins entered the portal vein and the right pulmonary veins were atretic. A correct diagnosis was made by detecting high-oxygen saturation in the hepatic veins, right-to-left shunt at atrial level, and increased pulmonary artery wedge pressure in comparison with the left atrial pressure, and was confirmed by angiography.

Kinetics of Oxygen Binding to Human Hemoglobin: TEMPERATURE JUMP RELAXATION STUDIES

Abstract The kinetics of oxygen binding to human hemoglobin at pH 7, 0.1 m phosphate, 20°, 2.5 x 10-5 to 10-3 m heme has been investigated by chemical relaxation methods in order to obtain information about the elementary steps and the mechanism of the cooperative process of ligand binding. The temperature jump relaxation method allows the oxygen-binding reaction to be followed over its entire time range. The relaxation process is characterized by two phases which are well separated in time. Both the time constants and the relative amplitudes are dependent on protein and ligand concentration. The two relaxation phases can be understood qualitatively. The fast phase corresponds at low oxygen saturation mainly to the binding of the first ligand molecule and at high saturation mainly to the binding of the last ligand molecule. At intermediate oxygen saturation the fast phase is determined predominantly by the kinetics of both the first and the last step—the intermediate reaction steps do not contribute significantly. The slow relaxation phase involves all elementary binding reactions, but is determined mainly by the kinetics of the intermediate oxygen-binding steps. The relative amplitudes of the fast and the slow relaxation phases reflect strongly the population of the reaction species involved. It is concluded that hemoglobin species with one and three ligands bound must be populated measurably at equilibrium. Reaction models which assume negligible concentrations of these intermediates are therefore not valid. Three reactions have been characterized directly by their kinetic properties: (a) a fast reaction step at low oxygen saturation yielding an apparent off-rate constant of about 1000 s-1 and an apparent on-rate constant (per tetramer) of about 4 x 107 m-1 s-1; (b) a fast reaction step at high oxygen saturation, yielding an apparent on-rate constant of about 4 x 107 m-1 s-1; (c) a slow reaction, which at high oxygen concentration yields an apparent rate constant of 5 x 106 m-1 s-1. It thus appears that the binding of the first oxygen molecule to deoxyhemoglobin is a very rapid process which is characterized by an apparent rate constant as large as that found for the binding of the last oxygen molecule. The low oxygen affinity of deoxyhemoglobin arises mainly from the high dissociation rate constant, i.e. short lifetime, of Hb4O2. It cannot be decided if these kinetic properties apply equally to both the α and β chains or if only one type of chain is involved in the fast phase of the relaxation spectrum. A four-step binding model (Adair scheme) explains quantitatively the principal observations of the relaxation kinetics. Adair rate parameters have been obtained which describe the appearance of two relaxation phases only, the ligand concentration dependence (from 0 to 250 µm O2), the protein concentration dependence (from 2 x 10-5 to 10-3 m heme), and the relative and absolute relaxation amplitudes of both phases. The calculated stopped flow kinetic progress curve, using these values, is in agreement with the available data (which are in the saturation range greater than 50%) and predicts a biphasic time course, in contrast to the kinetics of CO-binding. A decision between mechanisms based upon the relaxation kinetics data can be made only with certain assumptions. The values of the Adair-recombination rate constants exclude a mechanism in which there are two very rapidly interconverting structure forms of the protein, each exhibiting equal or nearly equal intrinsic kinetic and equilibrium properties for the four subunits. A concerted mechanism might apply if structure changes are not very fast compared to ligand binding or, if the kinetic properties of the α and β chains are markedly different. However, no consistent fit of the relaxation spectrum has been obtained so far with these assumptions.

Water circulation and nutrients in the North-west Irish Sea

The results of hydrographic observations made in the Irish Sea to the west of the Isle of Man during 1954–1961 and 1965–1968 are presented and discussed. The picture that emerges suggests that an appreciable part of the main south-north flow through the Irish Sea passes to the west of the Isle of Man. The core of high salinity water (as defined by the isohalines) can be associated with the deep trough, especially in the early part of the year, but more often than not is biased towards the Isle of Man. The salinity pattern in June 1955 may be interpreted in support of Williamson's (1956) suggestion that the flow through the Irish Sea is irregular. There is evidence that Atlantic water, although considerably diluted by fresh water run-off, penetrates southwards off the Irish coast. In winter hydrographic conditions tend to exhibit vertical uniformity, but bottom water of higher salinity which is also distinguishable by small temperature differences may sometimes be present. Occasionally there may be a very marked vertical discontinuity (as in March 1966) which is not only distinguishable by temperature and salinity differences but also by an inverse concentration of nutrient salts. Such an inverse relationship becomes completely obscured as a result of phytoplanktonic activity in the spring. During summer, surface warming brings about marked temperature layering which persists and consolidates in the region characterized by weak tidal currents. In particular, the area to the south west of the Isle of Man becomes very stable, although perhaps not completely stagnant as suggested by Simpson (1971). It is still possible for the denser bottom water to flow gradually northwards and replacement to take place at intermediate depths, below the surface mixed layer. Associated with the temperature layering is a well defined pattern of nutrient, dissolved oxygen and chlorophyll a distribution. Nutrient depletion occurs in the upper 30 m of the water column and may occasionally extend to greater depths. In particular, nitrate virtually disappears during the summer and would thus seem to be the limiting nutrient. Coinciding with the fall in nutrients is a rise in oxygen saturation. The highest chlorophyll a concentrations, however, tended not to coincide with the highest oxygen saturations, and may thus be indicative of dead or dying phytoplankton accumulating beneath the surface mixed layer. In the deep bottom water of the trough nutrient concentrations remain high and low oxygen saturations suggest that this is due to regenerative processes. Nitrite differs from other nutrients in that once the surface mixed layer has become established, a well defined maximum tends to occur at some depth beneath it. Following the breakdown of temperature layering the autumnal overturn distributes nutrients evenly throughout the water column. Nitrite can be particularly high at this time but declines rapidly as nitrate and other nutrients increase.

The ventilatory response to hypoxia during exercise in cyanotic congenital heart disease.

1. In contrast to the diminished ventilatory response to hypoxia which has been found at rest in cyanotic congenital heart disease, hyperventilation was noted on exercise in children who were cyanosed. 2. Sixteen children had low arterial oxygen saturations on exercise and thirteen of these hyperventilated by an amount similar to that reported in normal adults breathing hypoxic gas mixtures. 3. The three children who had little ventilatory response in relation to the increase of hypoxia during exercise all had a triad of long-standing cyanosis starting early in life, high haemoglobin concentration and low arterial oxygen saturation at rest in air.

Hepatic blood flow in alcoholic liver disease measured by an indicator dilution technic

Indicator dilution curves recorded from hepatic venous blood after selective injection of I 131 albumin into the hepatic artery were used to calculate hepatic blood flow in four normal subjects and forty-five patients with alcoholic liver disease. In fourteen patients with acute alcoholic hepatitis, hepatic blood flow was significantly higher (average 1,170 ± 94 [SEM] ml/minute/M 2) than in normal subjects (average 669 ± 62 ml/minute/M 2) or in twenty-four patients with chronic alcoholic liver disease (average 870 ± 76 ml/minute/M 2). In seven patients with preterminal hepatic failure hepatic blood flow averaged 982 ± 202 ml/minute/M 2. The hepatic fraction of cardiac output averaged 24.6 per cent in normal subjects and 25.9 per cent in those with alcoholic hepatitis, but it was significantly reduced in patients with chronic liver disease (average 19.3 per cent) and hepatic failure (average 20.1 per cent). Hepatic plasma volume also was higher in patients with alcoholic hepatitis (average 436 ml) than in the normal subjects (average 364 ml), the patients with chronic alcoholic liver disease (average 365 ml) or the patients with hepatic failure (average 336 ml). Despite the normal or high hepatic blood flow in most patients with alcoholic liver disease, abnormally high hepatic venous oxygen saturation was indicative of reduced splanchnic oxygen consumption in patients with alcoholic hepatitis and in those with hepatic failure compared to the normal subjects. A significant correlation between arteriovenous oxygen difference and hepatic albumin mean transit time suggests that intrahepatic shunting of oxygen could be a factor contributing to impaired hepatic function.

Biochemical changes in the blood during hypothermic cardiac arrest and recovery of rats.

<h2>Abstract</h2> The inferior vena caval blood from anaesthetized rats which recovered from 30 min cardiac arrest was compared with blood from rats which would not recover. It was found that high oxygen saturation, low K⁺ and low phosphate concentrations favoured recovery. Hypocapnia, acidaemia, high lactic acid concentrations, high blood creatinine and high urea concentrations were found in rats which recovered spontaneous respiration, and thus these do not constitute bad prognostic signs. Recovered rats had high haematocrits.

CONGESTIVE HEART FAILURE FROM INTRACRANIAL ARTERIOVENOUS FISTULA IN INFANCY

The clinical recognition of an intracranial arteriovenous fistula in a newborn infant depends on finding good peripheral pulses, a hyperdynamic cardiac impulse, cardiomegaly, and a cranial bruit. Dilated scalp veins and visible vascular malformations over the head will point toward the diagnosis. Cardiac catheterization can be diagnostic through recognition of a wide pulse pressure in combination with high oxygen saturations in the jugular veins and the right heart chambers. Cerebral angiography provides required anatomic detail. Surgical clipping of the feeding arteries may be helpful and even curative.

The influence of hyperbaric oxygen toxicity on renal preservation

Summary Fifty baboon kidneys were subjected to isolated bloodless perfusion, either immediately on removal or after 24-hr renal preservation. During perfusion these kidneys were exposed to either high oxygen saturation, low oxygen saturation, or helium, for complete anoxia. In comparison, kidney function was better in kidneys exposed to helium than when exposed to the high oxygen saturation. The best kidney function of the three groups, however, was maintained in those exposed to low oxygen saturation. In the high oxygen-saturated groups, renal resistance figures were high and intrarenal circulation was worse than in the other groups, indicating possible vasoconstrictive effects due to the high oxygen exposure. In the kidneys preserved for 24 hrs prior to perfusion, renal function was generally lower than in the immediately perfused kidneys. Of those preserved, the helium-exposed kidneys showed better results than the oxygen-exposed kidneys.

Displaced Bronchus, Lung Abscess and Retrograde Perfusion

The bronchus to a portion of lung in the right apex, which contained a large abscess, was found to arise from the right mainstem bronchus just proximal to the right upper lobe bronchus. Because bronchographk studies showed only anterior and posterior segmental branches arising from the right upper lobe bronchus, the abnormally placed bronchus was interpreted as a displaced apical segmental bronchus. During routine pulmonary angiography, the artery to the segment containing the abscess was not visualized. However, it was possible to catheterize this vessel selectively. Retrograde blood flow through the diseased segment was indicated by the demonstration that blood withdrawn from the segmental artery had a high oxygen saturation and by showing reflux of contrast material injected into the vessel. This finding indicates that failure to fill a segmental pulmonary artery during angiography may be caused by retrograde flow in the vessel, as well as by obstruction.