PO2 Gradient Research Articles

Direct estimation of intracellular PO2 gradients in a single cardiomyocyte of the rat.

In a previous study, we have demonstrated that microspectrophotometry coupled with a digital image processing is able to determine fractional binding of oxygen to myoglobin in an individual single cardiac myocyte isolated from the ventricles of the rat (Takahashi and Doi, 1995). Using this technique, we have determined the oxygen pressure (Po2) gradients from the extracellular space to cytosol in a quiescent cardiomyocyte (Takahashi and Doi, 1996). We also found that the Po2 gradients diminish as the cell becomes hypoxic (Takahashi and Doi, 1996). This reduction of Po2 gradients may partially restore the oxygenation of the intracellular space so that oxygen supply to mitochondria required for minimal electron flux through the respiratory chain is maintained even in severe hypoxia. We, however, were not able to quantitate the relative contributions of the extracellular (from extracellular medium to sarcolemma) and intracellular (from the sarcolemma to cytosol) Po2 gradients in the control of intracellular Po2. Thus, we undertook the present study to directly assess the magnitude of intracellular Po2 gradients with a subcellular spatial resolution in the single isolated cardiomyocyte.

Temporal fluctuations and spatial gradients of environmental PO2, temperature, H2O2 and H2S in its intertidal habitat trigger enzymatic antioxidant protection in the capitellid worm Heteromastus filiformis

MEPS Marine Ecology Progress Series Contact the journal Facebook Twitter RSS Mailing List Subscribe to our mailing list via Mailchimp HomeLatest VolumeAbout the JournalEditorsTheme Sections MEPS 163:179-191 (1998) - doi:10.3354/meps163179 Temporal fluctuations and spatial gradients of environmental PO2, temperature, H2O2 and H2S in its intertidal habitat trigger enzymatic antioxidant protection in the capitellid worm Heteromastus filiformis Doris Abele1,2,*, Heike Großpietsch1,2, Hans O. Pörtner2 1University of Bremen, Fachbereich 2, Marine Zoology, Leobener Str./NW2, D-28359 Bremen, Germany 2Alfred Wegener Institute for Polar and Marine Science, Bio 1, Box 120161, Columbusstr., D-27568 Bremerhaven, Germany *Please address correspondence to the Alfred Wegener Institute address. E-mail: abele@awi-bremerhaven.de Activity levels of 2 antioxidant enzymes, catalase (CAT) and superoxide dismutase (SOD), and the rate of oxygen consumption were investigated in body wall tissue of the capitellid polychaete Heteromastus filiformis in response to the variability of abiotic factors in the worm's intertidal habitat. A head-down deposit feeder, H. filiformis displayed oxyconformity between 1.3 and 13 kPa (10 to 100 torr) PO2 under laboratory conditions. An extremely low standard metabolic rate (SMR) equivalent to an oxygen consumption of 0.1 µmol O2 g-1 fw h-1 (fw = fresh weight) is consistent with the capacity of the worms to colonize anoxic and potentially sulphidic sedimentary environments. Maximal MO2 was 0.3 ± 0.09 µmol g-1 fw h-1 for small (<300 mg body fw) and 0.25 ± 0.09 µmol g-1 fw h-1 for large (>500 mg body fw) worms. CAT and SOD activities were higher in summer than in winter worms. Under laboratory conditions, SOD activity in winter worms was not inducible upon acclimation to elevated temperatures, while CAT activity was significantly higher at 20 than at 5°C. Summer worms were unaffected by temperature reduction with respect to CAT activities, while SOD activity was significantly reduced upon cooling. Under laboratory conditions, hypoxia as well as elevated PO2 led to a significant increase in CAT activity, while changes in SOD activity were marginal. Experimental hydrogen peroxide (H2O2) exposure resulted in an increase in CAT activity, whereas hydrogen sulphide (H2S) led to a decrease in CAT activity only if applied under anoxia. SOD activities of H. filiformis were insensitive to H2S in vivo. In situ exposure to elevated H2O2 concentrations confirmed that just 1 tidal emersion period was sufficient to cause the inducing effect of reactive oxygen species on CAT activities in the worms' natural habitat. It is concluded that short-term changes in CAT activity are triggered by specific environmental stress factors, like fluctuating PO2 and hydrogen peroxide concentrations in the upper sediment layer. In contrast, SOD did not respond spontaneously under experimental conditions, but under in situ conditions at the sediment surface of an intertidal sandflat a shift of SOD activity occurred towards the end of an ebb tide emersion period, which led to an increase of SOD activity in the tail compared to the head end of the worms. It is hypothesized that short-term variations in PO2 and temperature at the sediment surface, in combination with the vertical gradients of PO2, H2S, temperature, and pH, elicit the observed changes in SOD activity. Heteromastus filiformis · Antioxidant enzymes · PO2 · Temperature · Hydrogen peroxide · Hydrogen sulphide Full text in pdf format PreviousNextExport citation RSS - Facebook - Tweet - linkedIn Cited by Published in MEPS Vol. 163. Publication date: March 12, 1998 Print ISSN:0171-8630; Online ISSN:1616-1599 Copyright © 1998 Inter-Research.

Are there significant gradients of pO2 in cells?

It is widely recognized that the intracellular oxygen tension (pO2) plays an important role in cellular function and metabolism. In experimental and theoretical consideration involving the role of the pO2 the values that are used usually are those for the pO2 at the exterior of cells, because these values can be more readily measured. Such an approach is based on the assumption that the intracellular pO2 is very similar to the extracellular pO2 because oxygen freely diffuses across cell membranes and within cells, at a rate that is similar to that in the extracellular media. For the past several years we have been developing and applying electron paramagnetic resonance (EPR) techniques to test directly whether there are intracellular gradients of pO2 and if so, where they occur and what factors determine them. We previously reported significant gradients between the average pO2 in the intracellular and extracellular compartments in cell suspensions (Glockner 1989). More recently we developed techniques that enabled us to measure simultaneously the concentration of oxygen within a specific compartment, the phagosomes of activated macrophages, and the extracellular compartment and found gradients of up to 48 microM under some conditions (James 1995). The precise mechanism of the intracellular-extracellular oxygen gradient remains uncertain. The possibilities include that the diffusion of oxygen is not as free as assumed (e.g. that the cell membrane can act as a barrier) and the occurrence of active transport of O2 out of the cells. We report here on the use of a simple theoretical approach to evaluate the values of three key parameters which might account for the observed intracellular-extracellular oxygen measurements: (1) oxygen consumption; (2) the diffusion coefficient of oxygen in the cytosol; (3) the solubility of oxygen in the cytosol. We used two different models for the relationship between the oxygen consuming compartment (assumed to be primarily the mitochondria) and the intracellular compartment in which the measurements were made (especially phagosomes): uniform and non-uniform distribution of the mitochondria. Using these models and consensus values from the literature, we were unable to account for the experimentally observed differences in pO2 between the intracellular and extracellular compartments. Also we found that with the variation of any one parameter we could not plausibly account for the measurements made in the phagosomal and extracellular compartments. There are at least three logical possibilities to account for these results: 1) this methodology is erroneous and/or produces artifacts in the system resulting in invalid results; 2) the observation of a gradient in oxygen concentration between these two compartments arises from significant simultaneous variations of more than one of the critical parameters which are used conventionally to calculate potential gradients in pO2; 3) there is another factor not considered in the model which accounts for the observation (e.g. active transport; significantly higher than expected barriers to oxygen diffusion in the membrane).

A first estimate of the effect of catchment area on pO2 histograms derived from O2Mb saturation measurements.

When distribution of O2 in tissue is modelled in terms of diffusion, steep gradients in pO2 result locally. This is independent of the type of modelling and whether there is facilitated diffusion or not (Federspiel, 1986; Popel, 1989; Groebe, 1990; Hoofd, 1992; Bos et al., 1995). In particular around the capillaries, relatively large pO2 drops over a few urn are not rare. In tetanic dog gracilis muscle, these pO2 drops can be of the order of 5 kPa over less than 5 μm as nicely shown by Groebe (1990). Such predictions hitherto could not be confirmed experimentally, because of insufficient spatial resolution of the detection methods of measuring oxygen partial pressures directly.KeywordsGrid PointCatchment AreaOxygen TransportLarge CatchmentSaturation MeasurementThese 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.

Impact of diffusional oxygen transport on oxidative metabolism in the heart.

The resistance for the oxygen molecule to diffuse from the capillary blood to the cell surface produces remarkably large gradients of oxygen partial pressure (PO2) in the extracellular space. In addition, the intracellular radial gradients of PO2 may not be ignored particularly when the cellular oxygen consumption is increased. These PO2 gradients together result in a quite low intracellular PO2 in the cardiomyocyte in vivo. Thus, the cellular oxidative metabolism may be limited by diffusional transport of oxygen from the capillary blood to mitochondria. In this review, quantitative aspects and physiological relevances of the PO2 gradient in the myocardium are discussed.

Temporal fluctuations and spatial gradients of environmental PO2, temperature, H2O2 and H2S in its intertidal habitat trigger enzymatic antioxidant protection in the capitellid worm Heteromastus filiformis

Temporal fluctuations and spatial gradients of environmental PO2, temperature, H2O2 and H2S in its intertidal habitat trigger enzymatic antioxidant protection in the capitellid worm Heteromastus filiformis

Oxygen transport: air to muscle cell.

The series of drops in PO2 which comprise the oxygen cascade from the air to mammalian tissue can provide useful information about O2 transport during exercise in both health and disease, but the complete cascade has been challenging to study in vivo. This paper reviews a series of in vivo human knee-extensor studies which focus on the determinants of maximal O2 consumption (VO2max) in exercising muscle and concludes with a characterization of the complete O2 cascade in maximally exercising human muscle. Specifically, three issues have been addressed: 1) determinants of O2 extraction under conditions of very high muscle blood flow; 2) the role of O2 diffusivity in determining the maximum O2 flux rate (VO2max); and 3) myoglobin associated PO2 as a indicator of O2 transport and cellular respiration rate. In summary, these investigations demonstrate that in humans O2 extraction can be uncompromised despite high mass specific blood flows, perhaps in part because of an increased capillary density in exercise trained subjects. Exercise in hypoxia reduces VO2max, but as calculated diffusability of O2 from blood to muscle is constant. This suggests that a fixed O2 diffusivity plays a key role in limiting maximal O2 uptake. Supporting evidence of a substantial PO2 gradient from blood to myoglobin also suggests a resistance to the diffusion of O2 between red cell and sarcolemma, which may be present even at submaximal exercise. Finally, the proportionate relationship between myoglobin associated PO2 and VO2max in conditions of normoxia and hypoxia additionally supports the hypothesis that maximal respiratory rate of muscle cells is limited by O2 supply.

Physiological Strategies of Oxygen Transport in High Altitude Bird Embryos

Abstract Because of the relative simplicity of factors governing gas exchange between the embryo and the environment, the avian embryo has been extensively studied at sea level as a model for describing the physical principles that govern the physiology of gaseous diffusion. Two patterns of response have been observed in the oxygen pressure (PO2) cascade of high altitude avian embryos: (1) At a fixed O2 conductance, a decrease in metabolic rate below levels typical of conspecific species at sea level results in a reduction of ΔPO2 between ambient air and air cell. The decrease in metabolic rate also affects each step in the gradient until the mitochondria is reached. This is illustrated by a Fick's-type equation: P O 2 = V O 2 / G O 2 (GO2 = oxygen conductance); (2) Maintenance of metabolic rate at roughly sea level values and a large GO2 will also keep the ΔPO2 unmodified or even reduced. We have observed both patterns in mountain avian embryos in the Peruvian Andes. We measured VO2 and the ΔPO2 cascade of embryos of Peruvian coots (Fulica americana peruviana), which breed both at sea level and in the puna (Andean high altitude plateau), and those of Puna teal (Anas versicolor puna), a species that breeds solely in the puna, both at 4150 m. These two different strategies result in similar arterial PO2 values in both values in both embryos. Because the a-v PO2 gradient remains protected, the PVO2 values are also similar in the embryos of both high altitude birds.

Interstitial pH and pO2 gradients in solid tumors in vivo: high-resolution measurements reveal a lack of correlation.

The partial pressure of oxygen (pO2) and pH play critical roles in tumor biology and therapy. We report here the first combined, high-resolution (< or = 10 microns) measurements of interstitial pH and pO2 profiles between adjacent vessels in a human tumor xenograft, using fluorescence ratio imaging and phosphorescence quenching microscopy. We found (1) heterogeneity in shapes of pH and pO2 profiles; (2) a discordant relation between local pH profiles and corresponding pO2 profiles, yet a strong correlation between mean pH and pO2 profiles; (3) no correlation between perivascular pH/pO2 and nearest vessel blood flow; and (4) well-perfused tumor vessels that were hypoxic and, consequently, large hypoxic areas in the surrounding interstitium. Such multiparameter measurements of the in vivo microenvironment provide unique insights into biological processes in tumors and their response to treatment.

Oxygen transport to ischemic cardiac myocytes.

Po2 at mitochondrial innermembrane is determined by capillary blood Po2 and Po2 gradients between these two sites. The Po2 gradient of actively metabolizing tissue such as beating heart is considerably higher. Consequently, intracellular Po2 of the normal heart in situ may be as low as P50 of cytosolic myoglobin (2 ~ 5 Torr) (Coburn et al., 1973; Gayeski and Honig, 1991; Wittenberg, 1989). This cytosolic Po2 is still considerably higher than the apparent Km of cytochrome a,a3 and unlikely to interfere with the mitochondrial oxidative phosphorylation. In contrast to the normal state, the oxygen pressure gradient must be precisely regulated in the case of hypoxia, because, if oxygen pressure gradients remain constant, a decrease of capillary blood Po2 of a small magnitude (even 2 ~ 5 Torr) would deplete intracellular oxygen.

Stable High Conductivity Ceria/Bismuth Oxide Bilayered Electrolytes

We have developed a high conductivity bilayered ceria/bismuth oxide anolyte/electrolyte that uses the po2 gradient to obtain stability at the anolyte‐electrolyte interface and reduced electronic conduction due to the electrolyte region. Results in terms of solid oxide fuel cell (SOFC) performance and stability are presented. These results include a 90 to 160 m V increase in open‐circuit potential, depending on temperature, with the bilayered structure as compared to SOFCs fabricated from a single ceria layer. An open‐circuit potential of >1.0 V was obtained at 500°C with the bilayered structure. This increase in open‐circuit potential is obtained without any measurable increase in cell resistance and is stable for over 1400 h of testing, under both open‐circuit and maximum power conditions. Moreover, SOFCs fabricated from the bilayered structure result in a 33% greater power density as compared to cells with a single ceria electrolyte layer.

152 Identification of longitudinal tissue pO2 gradients as one cause for vascular hypoxia in window chamber tumors

152 Identification of longitudinal tissue pO2 gradients as one cause for vascular hypoxia in window chamber tumors

Regulation of oxygen diffusion in hypoxic isolated cardiac myocytes.

In the normal beating heart, oxygen pressure (PO2) gradients between capillary blood and intracellular space are so large that cytosolic PO2 may decline to around PO2 at half saturation of myoglobin (2-5 Torr). Hence, a decrease in capillary blood PO2 of a few Torr would easily deplete oxygen in mitochondria if PO2 gradients are unchanged. The aim of the present study was to demonstrate, in a single isolated cardiac myocyte of the rat, a mechanism that reduces PO2 gradients in hypoxia so that oxygenation of the intracellular space would be sustained. Using a newly developed microspectrophotometric device, we were able to follow changes in cytosolic PO2 of an individual ventricular myocyte in an hypoxic medium. For extracellular PO2 of 4.4 Torr, we found an elevation (2.1 Torr) of the cytosolic PO2 when oxygen consumption of the cell was abolished by 2 mM NaCN, thus demonstrating PO2 gradients from extracellular medium to cytosolic space in a single individual cardiomyocyte. The magnitude of these PO2 gradients was reduced as extracellular PO2 was further lowered, and they were no longer detectable for extracellular PO2 of 0.6 Torr. To further elucidate physiological effects of the PO2-dependent changes in PO2 gradients demonstrated above, we conducted a simulation of ischemia in a single cardiac myocyte. The stop-flow procedure (simulated ischemia) quickly decreased cytosolic PO2 from 7.3 to 1.8 Torr in 5 min, while the rate of fall of PO2 considerably decreased when the cytosolic PO2 decreased to < 2 Torr. Consequently, even 30 min after the onset of the stop flow, cytosolic PO2 was significantly higher than that of the anoxic perfusion. These results together suggest that in severe hypoxia oxygenation of the intracellular space might be partially maintained by relative elevation of cytosolic PO2, resulting from progressive decrease in PO2 gradients from extracellular space to cytosol.

Microvascular and tissue oxygen distribution

Understanding of oxygen delivery by the microcirculation has been dominated by the unitary component analysis of Krogh and Erlangen focussed on oxygen transport mediated by single capillaries, oxygenation of tissue as a whole being extrapolated from findings on oxygen exchange in these vessels. This analysis is under revision since capillaries are not sole sources of oxygen. It is increasingly apparent that arterioles are a significant equivalent source, while venules may serve as sinks for capillary and arteriolar oxygen. As a consequence detailed descriptions of the architecture of the microcirculation based on the tissue cylinder conceptualization does not yield new information given the non-exclusive role of capillaries as purveyors of oxygen to tissue. In the present study we investigate how tissue is oxygenated directly from the arteriolar supply on the basis of current results with newly developed optical techniques for the measurement of local intra- and extravascular pO2 by phosphorescence decay. This methodology shows that tissue regions between arterioles and venules have essentially uniform tissue pO2. The only experimentally detectable gradients in pO2 are those present in the immediate vicinity of arterioles. Findings on vascular longitudinal gradients are used to devise a model that links convective and diffusive processes, showing how blood viscosity, blood oxygen-carrying capacity and the slope of the oxygen dissociation curve are linked in determining intravascular and tissue pO2. The integrated approach provides a numerical basis for interpreting consequences of alterations in transport properties of blood applicable to the field of blood substitutes.

Determination of PO2 and its heterogeneity in single capillaries.

We have applied the phosphorescence lifetime technique (Vanderkooi, J. M., G. Maniara, T. J. Green, and D. F. Wilson. J. Biol. Chem. 262: 5476-5482, 1987) to determine oxygen tension in single capillaries of the hamster retractor muscle. Palladium meso-tetra(4-carboxyphenyl)porphine (10 mg/ml, pH 7.40, bound to bovine serum albumin) was used as the phosphorescent oxygen sensor. Our measurement system consisted of a microscope configured for epi-illumination, a strobe flash lamp, a 430-nm bandpass excitation filter, and a 630-nm cut-on emission filter. A rectangular diaphragm was used to limit the illumination field to 10 microns x 10 microns, and an end-window photomultiplier tube was used to detect the phosphorescence signal, which was then input to an analog-to-digital board in a personal computer. In vitro calibrations were carried out at 37 degrees C on samples flowing through a glass capillary tube (diameter, 300 microns) at four different O2 concentrations (0, 2.5, 5, and 7.5%). In vivo tests were carried out on arterioles, capillaries, and venules of the retractor muscle of anesthetized hamsters. The phosphorescent compound was administered by injection into a jugular vein (20 mg/kg). Phosphorescence decay curves were analyzed by a new model of heterogeneous oxygen distribution in the excitation/emission volume. Mean Po2 values and the local Po2 gradients within the excitation/ emission volume were calculated from phosphorescence life-times obtained from individual decay curves. The time course of Po2 obtained during 0.5-s measurement periods (5 decay curves at 0.1-s intervals) at a given site along a capillary indicated the presence of a gradient in Po2 within the plasma space between and near red blood cells. Similar Po2 gradients were also detected in arterioles and venules. Mean Po2 values for arterioles, capillaries, and venules over the 0.5-s observation period were 27 +/- 5, 14 +/- 2, and 11 +/- 3 (SD) mmHg, respectively. The magnitude of the Po2 gradient in the arterioles, capillaries, and venules was 6 +/- 1, 4 +/- 1, and 2 +/- 1 mmHg/micron, respectively.

The role of nitric oxide in subcutaneous and transmural gut tissue oxygenation.

The influence of inhibiting the nitric oxide (NO) synthetase on tissue perfusion as indicated by tissue oxygen tensions was determined. Tissue oxygen probes were placed subcutaneously and on serosal and mucosal surfaces of colon of anesthetized adult rats. After a control period, the inhibitor of NO formation, N(G)-nitro-L-arginine methyl ester (L-NMMA), was given intravenously and followed 20 min later by infusion of substrate for NO synthetase, L-arginine. Mean arterial blood pressure (MAP), subcutaneous tissue oxygen tension (P(SQ)O2), serosal tissue oxygen tension (P SO(2)), and mucosal tissue oxygen tension (P(M)O2) were simultaneously measured. Baseline values for the measured parameters were MAP = 95 + or - 9 mmHg, P(SQ)O2 = 61 + or - 7 mmHg, P(S)O2 65 + or - 7 mmHg, and P(M)02 = 9 + or - 2 mmHg. The infusion of L-NMMA induced a significant increase in MAP to 123 + or - 7 mmHg (p < .001) and P(SQ)O2 to 72 + or - 7 mmHg (p < .001). P(S)O2 did not change significantly from baseline after L-NMMA infusion. A significant decrease in P(M)O2 to 4 + or - 2 mmHg was noted after L-NMMA infusion (p < .001). The administration of L-arginine promptly returned all measured parameters to baseline levels within 10 min of infusion. A transmural P(O2) gradient exists across the colon with P(M)O2 far lower than P(S)O2. P(SQ)O2 approximates P(S)O2 at baseline and P(S)O2 is not altered by inhibition of the NO synthetase. The 45% reduction in mucosal PO2 after L-NMMA, which was reversed by L-arginine infusion, suggests that nitric oxide participates in splanchnic vasomotor control with a preferential effect in the mucosal vasculature. The observed decrease in mucosal PO2 observed after inhibition of NO production is similar to the worsened hypoxia previously measured during hemorrhagic shock. Further work clarifying the local control mechanisms of gut tissue P02 can direct therapies to increase gut tissue oxygenation.

Pulmonary function in rheumatoid arthritis treated with low-dose methotrexate: a longitudinal study.

Lung volumes and gas exchange were investigated prospectively in 96 patients with rheumatoid arthritis selected without regard to pulmonary disorders and treated with i.m. methotrexate (MTX) injections [mean weekly dose 13.0 mg (5th-95th percentile (5-95 PC) 7.6-20.8)]. Individual changes over time during MTX treatment [mean duration 2.9 yr (5-95 PC 0.4-5.3)] were assessed by regression analyses in each individual. Forced vital capacity (FVC) remained stable in the majority of patients [mean annual change +0.8% (5-95 PC -8.1 to +14.0) of calculated normal value]. In addition, transfer factor using the indicator gas CO (TL,CO) was unaltered in most patients [mean annual change -2.1% (5-95 PC -16.2 to +11.8) of predicted value]. However, there were significant decreases in the forced expiratory volume in 1 s (FEV1) before and after inhalation of 0.2 mg salbutamol [mean annual change -0.8% (5-95 PC -8.4 to +3.2) and -1.3% (5-95 PC -7.8 to +3.9) of the FVC measured, respectively]. In addition, there were significant increases in alveolar-arterial Po2 gradients (P(A-a),O2) at rest and after exercise [mean annual change +1.7 mmHg (5-95 PC -5.2 to +12.2) and +1.8 mmHg (5-95 PC -3.5 to 9.0), respectively]. Nevertheless, the amounts were small in view of the reliability of the methods applied and reflect, at least in part, the normal process of ageing. The annual change in FEV1/FVC was negatively correlated with FEV1/FVC at baseline (Rs = -0.46, P < 0.001). The annual change in TL,CO was also negatively correlated with TL,CO at baseline (Rs = -0.31, P = 0.028). No other risk factors for deterioration of lung volumes or gas exchange were found, including mean weekly MTX dose, age, gender, smoking, presence of rheumatoid factor and pulmonary function at baseline. We conclude that MTX has no major effect on pulmonary function in the majority of patients and that there is no evidence that patients with pre-existing pulmonary disease are at increased risk for further deterioration of lung function.

Systemic and subcutaneous microvascular oxygen tension in conscious Syrian golden hamsters.

Arteriolar and venular oxygen tension distribution was studied in the subcutaneous connective tissue of the chamber window preparation in conscious Syrian golden hamsters as a function of the systemic PO2, PCO2, pH, arterial pressure and hematocrit, microvascular red blood cell (RBC) velocity, vessel diameter, and blood flow in the same microvessels. PO2 was measured with the phosphorescence decay technique using Pd-meso-tetra(4-carboxyphenyl)porphyrin (30 mg/kg body wt iv). Systemic arterial and venous PO2s were 71.6 +/- 13.1 and 28.4 +/- 5.1 mmHg, while oxygen tension was 45.1 +/- 13.3 mmHg in arterioles and 30.1 +/- 10.7 mmHg in venules. The relatively low arteriolar PO2 and the small arteriolar-venular PO2 gradient indicate that some blood oxygen exits directly to the tissue or is shunted before reaching the capillaries. RBC velocity was the strongest correlate of microvascular PO2 (arterial correlation coefficient = 0.503 and venous correlation coefficient = 0.560, P < 0.001). Microvascular PO2 was also correlated with blood flow, vessel diameter, blood pH, and PCO2 but not with systemic PO2. Arterial oxygen tension was only significantly related to PCO2, pH, and hematocrit. These findings suggest that oxygen delivery to the tissue improves with increasing blood flow velocity and that microvascular PO2 is a locally regulated parameter in the absence of major systemic perturbations.

Transmural gut oxygen gradients in shocked rats resuscitated with heparan.

To develop a reproducible model to measure transmural gut tissue PO2, to determine the gradient from serosa to mucosa during normovolemia and hypovolemia, and to determine the effect of resuscitation with heparan sulfate (danaparoid sodium) on this gradient. Fluorescent tissue oxygen sensors were placed onto serosal and mucosal surfaces of rat colon. Hemorrhagic shock was induced using a fixed pressure (mean arterial pressure, 40 mm Hg) model and resuscitated with either saline solution or heparan. Control animals had stable mean (+/- SD) serosal and mucosal tissue oxygen tensions (PO2) of 64 +/- 4 and 10 +/- 2 mm Hg, respectively. In shocked animals, baseline serosal PO2 decreased to 37 +/- 2 mm Hg at a mean (+/- SD) of 19 +/- 7 minutes after the initiation of hemorrhage. Mucosal values decreased to a minimum of 4 +/- 2 mm Hg at 45 +/- 15 minutes after the initiation of hemorrhage. Serosal PO2 returned to baseline during resuscitation in both control and heparan-resuscitated animals. Mucosal PO2 did not return to baseline in the shock/no heparan group. In the heparan-resuscitated animals, however, mucosal PO2 increased above baseline (13 +/- 3 mm Hg at 3 hours after completion of hemorrhage). A transmural gradient of PO2 exists across the colon with mucosal PO2 far lower than serosal PO2. Both serosal and mucosal PO2 decrease during hypovolemia. During hypovolemia, the PO2 of the entire gut wall is in a range in which phagocytic killing is impaired by hypoxia. Heparan improved mucosal PO2 and it may restore and/or protect gut function by oxygen-related mechanisms.

Intraretinal oxygen distribution in rats as a function of systemic blood pressure

Differential responses to induced changes in systemic blood pressure (BP) at different layers of both the retinal and choroidal vasculature were observed, by monitoring localized PO2 as a function of depth, in the retina and choroid of the rat eye using oxygen-sensitive recessed microelectrodes. Visual and electrophysiological localization of the microelectrode tip allowed the oxygen distribution to be related to the positions of the vascular beds of the retina and choroid. Highly reproducible intraretinal PO2 profiles were achieved. The relationship between PO2 and systemic BP was linear in the deep capillary layer of the retina (PO2 = 0.17 x BP - 2.63) and in the choriocapillaris (PO2 = 0.21 x BP + 2.95), whereas it was nonlinear in the superficial retinal capillary layer [PO2 = 40.01/[1 + (BP/66.22)-1.22]] and deep choroid [PO2 = 83.82/[1 + (BP/124.61)-0.87]]. The minimum PO2 occurred between the two retinal capillary beds, and a PO2 gradient was evident in the choroid. The contrasting responses of different layers of the two circulations reflect different blood flow control mechanisms not evident when studying the circulations as a whole.