Tissue Oxygen Supply Research Articles

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.

Detection of ventilatory threshold using near infrared spectroscopy in men and women.

The onset of anaerobic (lactate) metabolism during incremental exercise, which may be a result of an imbalance between tissue oxygen supply and demand, has been associated with the gas exchange ventilatory threshold (VT). This study was designed to examine whether near infrared spectroscopy (NIRS) could be used to detect the VT in healthy subjects. Twenty-one men and 19 women completed incremental cycle ergometry during which NIRS measurements were obtained from the right vastus lateralis and gas exchange measurements were monitored simultaneously using a metabolic cart. The VT was identified from the metabolic data by the V-slope method and from NIRS data as the intensity at which tissue absorbency crossed the resting baseline value observed immediately prior to the initiation of exercise. Pearson correlations for the relative oxygen uptake and power output observed for the two methods of detecting VT were 0.90 and 0.88, respectively, in men and 0.89 and 0.86, respectively, in women (P < 0.01). No significant differences were observed between the two methods of detecting VT for any of the physiological responses (P > 0.05). No significant (P > 0.05) gender differences were observed in muscle oxygenation values at the VT, 32% in men and 38% in women. These results validate the use of NIRS as an alternate noninvasive method for detecting VT during cycle exercise in healthy subjects.

Tumor oxygenation under normobaric and hyperbaric hyperoxia. Impact of various inspiratory CO2 concentrations.

Tumor hypoxia is an important factor limiting the efficiency of sparsely ionizing ra-diation and O2-dependent chemotherapy. Since the tumor pO2 is the result of a dynamic steady state between oxygen supply and O2 consumption of the tumor tissue, hypoxia could be reduced either by increasing the O2-supply or by reducing the O2 demand of the tumor cells. The O2 supply can be improved for instance by (i) increasing the arterial oxy-gen partial pressure, (ii) improving (and homogenizing) the tumor perfusion, or (iii) en-hancing the O2 release from blood into the tissue by right-shifting the HbO2 dissociation curve. Theoretically, it should also be possible to improve tumor oxygenation by a rela-tively small decrease in O2 consumption rate of the tumor cells. However, at present in-creasing the arterial pO2 by breathing hyperoxic gas mixtures seems to be the most effective method to improve tumor oxygenation and, thus, to enhance the efficiency of standard radio- and chemotherapy in experimental malignancies [1,7,10,11,15,24] as well as in human tumors [3,9,12,14,22,29,30]. However, since in some tumor entities oxygena-tion is inadequate and anisotropic [27], normobaric hyperoxia is often not sufficient to completely eradicate tumor hypoxia [6,16,18,26]. In these cases only breathing of hyper-oxic gases under hyperbaric conditions may be sufficient to lead to therapeutic results. On the other hand, studies on experimental tumors in animals as well as clinical trials in pa-tients showed non-uniform results concerning the therapeutic benefit of inspiratory hyper-oxia ranging from clear improvement of radiosensitivity [3,4,20,30] to no effect on therapeutic outcome [3,4]. Finally, enhancement of tumor growth by hyperbaric oxygenation has been discussed [13,23].

Brain metabolic and vascular adaptations to hypoxia in the rat. Review and update.

Prolonged exposure to low oxygen environments provokes systemic adaptations that result in maintained oxygen delivery to the brain, and central cerebrovascular and metabolic adaptations that preserve tissue oxygen and energy supply to support neuronal function. Recently, we have examined a number of aspects of the central nervous system adaptation to mild hypoxia, and though these studies provide a far from complete understanding of the phenomenon, some general conclusions can at least be drawn.KeywordsChronic HypoxiaHypobaric HypoxiaHypoxic ExposureCytochrome Oxidase ActivityMild HypoxiaThese keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Geometry of the capillary net in human hearts.

The geometry of the coronary capillary bed in human hearts was studied using samples obtained during cardiac surgery of children operated for tetralogy of Fallot and samples from fresh normal hearts used for valve harvesting. The results revealed a similar coronary capillary density and heterogeneity of capillary spacing in samples from both groups. A double-staining method was used to distinguish between capillary segments close to the feeding arteriole (proximal capillaries) and segments distant from the arteriole (distal capillaries). In both groups of hearts, capillary segment length was consistently shorter on the venular than the arteriolar portion of the capillary. Similarly, capillary domain areas were also smaller and the resulting capillary supply unit was smaller along venular portions compared to arteriolar regions of the capillary bed. This distinctive geometry would provide advantageous geometric conditions for tissue oxygen supply.

Catchment depths of surface electrodes for H2 and O2 in tissue.

Polarographic electrodes have been used for many years to measure oxygen partial pressure (pO2) in various organs and tissues, often in animal experiments, and have greatly contributed to the understanding of local mechanisms controlling tissue oxygen supply. Five years ago we reported the use of a hydrogen clearance technique using a multichannel electrode (Kessler & Lubbers, 1966, multiwire surface electrode, MDO) adapted to the detection of partial pressure of hydrogen (pH2) in order to measure capillary blood flow in skeletal muscle (Harrison & Kessler, 1989a). This development meant that measurements of both blood flow and pO2 could be made in similar volumes of tissue. Furthermore, methods were devised whereby local O2 uptake rate could be calculated (Harrison et al. 1989; Harrison et al. 1990).

Red Blood Cell Spacing in Rat Coronary Capillaries during the Cardiac Cycle

Theoretical studies have demonstrated a pronounced effect of red blood cell (RBC) spacing on tissue oxygen supply. Our objective was to collect data regarding RBC spacing and related linear capillary hematocrit (Hct) in rat coronary capillaries, from two distinct locations within the capillary bed (proximal and distal portions), in the subendo- and midmyocardium, during systole and diastole. Hearts were rapidly frozenin situ,and tissue sections were stained in order to distinguish capillaries in proximal and distal portions of the capillary bed, as well as the RBCs within them. Morphometric data were compared according to capillary type, cardiac region, and cardiac phase. Distal portions of the capillary bed had a significantly greater capillary Hct (P< 0.001) and significantly lower RBC spacing values (P< 0.01), compared to proximal portions, irrespective of cardiac phase or region. There was a greater frequency of RBC spacing values equal to 0 μm in systole compared to diastole (P< 0.001) and a greater frequency of RBC spacing values greater than 40 μm in proximal portions of the capillary bed compared to distal portions (P< 0.001). These results suggest that intracapillary resistance to O2transport is reduced, and O2carrying capacity of the blood increased, in distal portions of the capillary bed, where PO2in the blood is lower.

Identification of a putative microvascular oxygen sensor.

The vascular response to changes in oxygen levels in the blood and tissue is a highly adaptive physiological response that functions to match tissue oxygen supply to metabolic demand. Defining the cellular mechanisms that can sense physiologically relevant changes in PO2 and adjust vascular diameter are vital to our understanding of this process. A cytochrome P450 (P450) enzyme of the 4A family of omega-hydroxylases was localized in renal microvessels, renal cortex, and a striated muscle microvascular bed (cremaster) of the rat. In the presence of molecular oxygen, this P450 enzyme catalyzes formation of 20-HETE from arachidonic acid (AA). Prior studies have shown that 20-HETE potently contracts renal and cerebral arteries and arterioles. The present study demonstrates that 20-HETE constricts striated muscle arterioles as well. In both intact renal microvessels and enriched renal cortical microsomal enzyme preparations, the formation of 20-HETE was linearly dependent on PO2 between 20 and 140 mm Hg. Homogenates of cremaster tissue produced 20-oxygen HETE when incubated with AA. They also expressed message for P450 4A enzyme, as determined by Southern and Western blots. Administration of 17-octadecynoic acid (17-ODYA), which is a P450 4A inhibitor, attenuated the constriction of third-order cremasteric arterioles in response to elevation of superfusion solution PO2 from approximately equal to 3 to 5 mm Hg to approximately equal to 35 mm Hg. 17-ODYA had no effect on basal vascular tone or response of cremaster arterioles to vasoactive compounds. These results demonstrate the existence of P450 omega-hydroxylase activity and 20-HETE formation in the vasculature and parenchyma of at least two microvascular beds. Our data suggest that a P450 enzyme of the 4A family has the potential to function as an oxygen sensor in mammalian microcirculatory beds and to regulate arteriolar caliber by generating 20-HETE in an oxygen-dependent manner.

Critical Care Medicine

Shock and multiple organ system failure are 2 of the most common and important problems in the intensive care unit (ICU). When tissue oxygen supply decreases in certain forms of shock, increased oxygen extraction occurs to maintain oxygen consumption. If shock continues unabated, oxygen delivery becomes inadequate and anaerobic metabolism ensues, with lactic acidosis. After this critical point, oxygen consumption is said to be delivery-dependent. The blood lactate level correlates well with the degree of perfusion failure and reflects the oxygen debt. In shock due to trauma, hypovolemia, or hemorrhage, it has long been recognized that rapid and aggressive resuscitation results in quicker repayment of this oxygen debt and improved outcome. Some critically ill patients, notably those with trauma or sepsis, are hypermetabolic and may require higher levels of oxygen delivery to maintain oxidative metabolism. Accordingly, it has been hypothesized that increasing oxygen delivery to supranormal levels may be beneficial.

The Erlanger Microlightguide Photometer: a new concept for monitoring intracapillary oxygen supply of tissue--first results and a review of the physiological basis.

The local oxygen supply to the skin immediately before and after withdrawal of blood was appraised in 18 healthy test subjects by measuring the intracapillary hemoglobin oxygenation (HbO2). The investigation was carried out with the Erlanger Microlightguide Photometer (EMPHO). EMPHO measurements are based on the registration of tissue remission spectra from which the HbO2 values are calculated using the Kubelka-Munk theory. The results show that global parameters do not reflect the supply of oxygen to the tissue; for example, in hypovolemia, the physiological response to the pathophysiological stimulus is centralization. This is manifested at a very early stage in the skin, before the oxygen supply to other organs (e.g., liver, kidney, gut) is affected. The disturbance of the local cutaneous oxygen supply is reflected in a change in the intracapillary hemoglobin oxygenation of the skin. Hence, one might consider measurements of the local oxygen supply to the skin as an early indicator for centralization.

Anaemia and Haemoglobin Status: A New Concept and a New Method of Assessment

Traditionally, anaemia has been determined and interpreted by the magnitude and severity of iron deficiency and the impact of intervention strategies. Internationally, it is defined as a state in which the quality and/or quantity of circulating red cells are reduced below a normal level The body employs several mechanisms during the development of anaemia to maintain the oxygen supply to the tissues. Thus, applying any quantitative cut-off point as an indicator for anaemia may lead to misclassification, since haemoglobin concentration does not necessarily reflect the level of tissue oxygen supply. Ideally, an assessment strategy should be able to determine both the degree of haemoglobin oxygenation and the haemoglobin concentration at a tissue level. The Erlangen microlight-guide spectrophotometer is a non-invasive instrument that can assess both capillary blood oxygenation and relative haemoglobin concentration.

Increased antioxidant capacity, suppression of free radical damage and erythrocyte aggrerability after combined application of alpha-tocopherol and FC-43 perfluorocarbon emulsion in early postburn period in rats.

Certain rheological disorders such as enhanced aggregation and reduced deformability of erythrocytes are closely associated with microcirculatory disturbances, decreased tissue oxygen supply and represent a major problem in severely burnt patients [1-4]. Vitamin E (alpha-tocopherol) and vitamin A (retinol) exert an important plasma antioxidant properties against free radical-induced damage [11,12]. They possess chain-breaking properties and act as synergists [13]. Plasma antioxidant capacity may be decreased in severely burnt patients as a result of the enhanced consumption and inadequate restoration of antioxidants in the conditions of activated peroxidative process [14]. Treatment with alpha-tocopherol suppresses lipid peroxidation in blood and therefore improves erythrocyte rheology [15]. Perfluorocarbon emulsions improve microcirculation and rheological blood properties [16-18] and preserve the structure and function of endothelial cells [19]. The very small particle size, low viscosity and high oxygen carrying capacity ensure their penetration into the microvasculature even under conditions of ischemia and acidosis [20, 21]. Perfluorocarbons have been reported to inhibit leukocyte activation and superoxide radical production [22]. The aim of the present study was to examine the antioxidant capacity, free radical mediated damage and erythrocyte aggregation in plasma of rats with thermal skin injury in the early postburn period and to evaluate the effect of treatment with alpha-tocopherol and FC-43 perfluorocarbon emulsion alone and in combination. We might conclude that thermal skin injury in rats reduces the antioxidant capacity, enhances free radical mediated damage and erythrocyte aggregation on the third hour after injury. The combined application of alpha-tocopherol and FC-43 perfluorocarbon emulsion immediately after thermal skin injury in rats increases plasma antioxidant capacity, decreases free radical mediated damage of erythrocytes and suppresses their aggregation on the third hour after the injury.

Oxygen electrodes and optodes and their application in vivo.

In the 1940s it was well known that the transport of oxygen within the tissue occurs by diffusion. Since by diffusional transport oxygen pressure gradients develop, the state of tissue oxygen supply can be characterized by the distribution of local pO2. At that time, however, it was only possible to measure mean tissue pO2. This was done by introducing e.g. a small gas bubble into the tissue1. After equilibration the bubble was withdrawn and analyzed by gas analysis. It was tried to understand these measurements by applying the cylindrical tissue model of Krogh2,3, but these measurements did not help much to understand the physiological presuppositions of anoxia or hypoxia because local tissue measurements were missing. The situation was changed when in 1942 P.W. Davies and F. Brink published their paper on “Microelectrodes for Measuring Local Oxygen Tension in Animal Tissue”4. This work was done in the laboratory of D.W. Bronk at the Johnson Foundation in Philadelphia, USA. The authors describe in great detail manufacturing and application of polarographic pO2 electrodes with a sensor surface of only 25 μm. Such a small sensor surface was needed because their aims were to measure “variations of oxygen tensions over small distances in tissues” to locate “sites of oxygen consumption by mapping concentration gradients” or “to measure the oxygen tension in blood of superficial arterioles and venules of the cat cerebral cortex, in the cortical substance itself, at the surface of muscle cells and at various distances from the surface of single celled organs”. About the development of this sensor Roseman, Goodwin and McCulloch mention in a footnote of their paper,5 that qualitative and quantitative polarographie analysis “was first employed in Dr. Bronk’s laboratory. By this method Brink and Davies determined the metabolism of the excised nerve.

Pathophysiology of the microcirculatory bed in obesity

A total of 207 patients with alimentary constitutional and hypothalamic obesity were examined in order to assess the status of the microcirculatory bed, including the status of capillary walls, hemocirculation, transcapillary metabolism, oxygen delivery to tissues in patients with various forms of obesity. Bulbobiomicroscopy, assessment of capillary wall permeability by the hydrostatic test, polarographic study of oxygen tension in the skin using oxygen and ischemic test were employed. Obese patients were found to develop appreciable microcirculatory disorders (vascular, intravascular, extravascular); capillary walls became better penetrable for liquid and proteins and the adaptation reserve of these vessels decreased, with the substrate movement from blood to tissues predominating. A correlation has been traced between the status of the circulation and capillary walls, and extravascular shifts, on the one hand, and capillary permeability, on the other. Oxygen delivery to tissues was disordered in obese patients, this manifesting by deterioration of both oxygen delivery and consumption. The degree of impairment of various components of microcirculation and oxygen supply of tissues augmented with body mass increase.

Near infra-red spectroscopy: a non-invasive monitor of perfusion and oxygenation within the microcirculation of limbs and flaps

Reliable early detection of adverse circulatory changes within a flap following free tissue transfer and early re-exploration are vital to minimise flap failure. Most surgeons rely on clinical assessment to monitor these changes but techniques such as plethysmography and laser Doppler have their advocates. These methods are limited however to measuring changes close to the surface. Near infra-red spectroscopy (LAIRS) is a relatively new, non-invasive technique which allows continuous monitoring of concentration changes in oxy-, deoxy- and total haemoglobin (HbO 2, Hb and HbT), as well as oxidised cytochrome aa 3, through tissue up to 10 cm in depth. Information is provided on tissue oxygen supply, cellular oxygen utilisation, blood volume and perfusion status. A study ahs been performed in 10 rabbit hind limbs to assess the ability of NIRS to detect and distiguish between venous, arterial and total vascular occlusion. Clear patterns of change have been identified which allow rapid detection of vascular occlusion with accurate prediction of site. Arterial occlusions were characterised by an increase in Hb with a corresponding decrease in HbO 2 and HbT. Venous occlusions resulted in an increase in HbT with relatively minor fluctuations in Hb and HbO 2 Simultaneous occlusion of both artery and vein produced similar changes to those of arterial occlusion except that HbT decreased only minimally. These findings suggest that LAIRS has a potentially useful role in the monitoring of free flaps, with the great advantage that perfusion can be measured to a considerable depth and information provided on the oxygenation profiles both accurately and non-invasively.

Red Blood Cell Function in Hypoxia at Altitude and Exercise

Oxygen transport by red blood cells is regulated by erythropoiesis and Hb-O2-affinity. The O2 carrying capacity is characterized by changes in hematocrit, red blood count or the mass of circulating red blood cells. Erythropoiesis is controlled by the hormone erythropoietin, which induces slow changes of the O2-transport capacity. The Hb-O2-affinity is modified mainly by pH and 2,3-DPG. Despite their apparently diverse effects e.g. in hypoxia at high altitude, a compromise seems to be adopted optimizing both arterial O2-loading and peripheral O2-unloading. In contrast to erythropoiesis, adjustments of the Hb-O2-affinity occur fast and allow rapid adjustments of O2-binding and release. In the intact organism the significance of changes in Hb-O2-affinity for tissue oxygen supply relative to adjustments of cardiac output, microcirculation and O2-transport capacity is not completely understood yet, but beneficial effects were demonstrated in isolated organs. It is, however, the least energy-demanding way of optimizing tissue O2-supply, which might be of significance in extreme situations. In severe hypoxia adjustments of both, hematocrit and Hb-O2-affinity, are insufficient to maintain tissue O2-supply. Alterations of Hb-O2-affinity are also insufficient to compensate for severe anemia.

Acute normovolaemic haemodilution and idiopathic scoliosis surgery: effects on homologous blood requirements.

After the introduction of acute normovolaemic haemodilution(NVHD) in our hospital, we prospectively studied 19 patients managed with moderate NVHD (mean haematocrit 0.28, SD 0.02) during idiopathic scoliosis surgery (mean angle 53.2, SD 16.7 degrees) with the Cotrel-Dubousset instrumentation (CDI). Our standard scoliosis anaesthetic technique was used. Intraoperatively, one patient received one unit of homologous blood. Postoperatively, seven patients received ten units of homologous blood. Homologous blood used was reduced by about 83% for this procedure in our institution. In the assessment of fluid and blood requirements we found physical signs reflecting tissue perfusion and oxygen supply more reliable than the estimated blood loss using the suction bottle and swabs. The similar postoperative complications (nine fever, five atelectasis/pneumonia, one urinary infection, one phlebitis), anaesthetic duration (mean 5.21, SD 1.13) hours, hospitalisation (mean 6.67, SD 1.19) days and return to normal activity (mean 8, SD 7.68) weeks indicate that the NVHD patients did just as well as with our previous regimen when only homologous blood was used.

Effects of the correction of renal anaemia by erythropoietin on physiological changes during exercise

The effects of treating the anaemia of end-stage renal failure with erythropoietin were studied in nine dialysis patients. The increase in haemoglobin concentration (by 59% from 7.0 +/- 1.2 to 11.1 +/- 1.1 g dl-1) was associated with increases in exercise duration (by 41%) and maximum oxygen consumption (by 34%). Treatment reduced resting heart rate but did not significantly alter heart rate at maximum exercise, nor resting or exercise blood pressure. Resting arterial potassium concentrations were slightly increased after treatment, but they increased similarly in relation to minute ventilation during exercise. Lactic acidaemia developed during exercise at both levels of haemoglobin, and was accompanied by similar reductions in arterial pH and bicarbonate levels but constant PaO2 and PaCO2. Ventilation was coupled to the metabolic rate of carbon dioxide production, ventilatory dead-space and arterial PCO2 before and after treatment of anaemia, the ventilatory requirement for carbon dioxide elimination being unchanged. Treatment of anaemia did not alter resting arterial lactate concentration; the concentration of lactate at maximum exercise was increased slightly following treatment but this increase did not reach statistical significance. The rate of increase in arterial lactate concentration as a function of oxygen consumption, assessed both with respect to the 'lactate threshold' and 'lactate slope index', was significantly delayed by treatment. Treatment of anaemia also delayed the 'anaerobic threshold', and there was good correlation between lactate and anaerobic thresholds. Treatment of renal anaemia by erythropoietin thus results in improved tissue oxygen supply during exercise, reflected by delay in the onset of lactic acidaemia.

Spectrophotometric measurements of haemoglobin saturation and concentration in skin during the tuberculin reaction in normal human subjects.

A non-invasive technique employing light-guide spectrophotometry is described for the measurement of haemoglobin concentration and oxygenation in human skin. Measurements were carried out in the visible wavelength range (500-620 nm) and a series of experiments were carried out in vitro and in vivo in order to calibrate the system. Indices were derived for the measurement of relative haemoglobin concentration and absolute oxygen saturation. The technique was applied to measure the changes in these parameters occurring during the course of the tuberculin reaction in human skin. The results are compared with those from laser Doppler flowmetry and transcutaneous oxygen measurements which were carried out concurrently. Divergence between the intracapillary and tissue oxygenation during the course of the reaction provides evidence for the existence of increased diffusion resistance for oxygen; a model is proposed. The study demonstrates the potential clinical usefulness of light-guide spectrophotometry for the non-invasive investigation of tissue oxygen supply.

Abnormal blood rheology in idiopathic dilated cardiomyopathy

Thromboembolic events represent a frequent complication in dilated cardiomyopathy. 1 Intracardiac thrombi occur in a high proportion of patients 2,3 and are primarily ascribed to a reduction in cardiac output with low intracardiac blood flow velocity. 4 Hemorrheologic factors are known to play an important role in the coagulation process, particularly in presence of low flow states. 5 Hemorrheologic abnormalities in patients with dilated cardiomyopathy may therefore favor the generation of intracardiac thrombi. Such abnormalities in patients with low cardiac output might even further compromise peripheral blood flow and thus reduce tissue oxygen supply. Therefore, rheologic parameters were studied in patients with idiopathic dilated cardiomyopathy and compared with a healthty control group.