Tissue Oxygen Consumption Research Articles

The microcirculatory response to compensated hypovolemia in a lower body negative pressure model

The objective of the present study was to test the hypothesis that controlled, adequately compensated, central hypovolemia in subjects with intact autoregulation would be associated with decreased peripheral microcirculatory diffusion and convection properties and, consequently, decreased tissue oxygen carrying capacity and tissue oxygenation. Furthermore, we evaluated the impact of hypovolemia-induced microcirculatory alterations on resting tissue oxygen consumption. To this end, 24 subjects were subjected to a progressive lower body negative pressure (LBNP) protocol of which 14 reached the end of the protocol. At baseline and at LBNP=−60mmHg, sidestream dark field (SDF) images of the sublingual microcirculation were acquired to measure microvascular density and perfusion; thenar and forearm tissue hemoglobin content (THI) and tissue oxygenation (StO2) were recorded using near-infrared spectroscopy (NIRS); and a vascular occlusion test (VOT) was performed to assess resting tissue oxygen consumption rate. SDF images were analyzed for total vessel density (TVD), perfused vessel density (PVD), the microvascular flow index (MFI), and flow heterogeneity (MFIhetero). We found that application of LBNP resulted in: 1) a significantly decreased microvascular density (PVD) and perfusion (MFI and MFIhetero); 2) a significantly decreased THI and StO2; and 3) an unaltered resting tissue oxygen consumption rate. In conclusion, using SDF imaging in combination with NIRS we showed that controlled, adequately compensated, central hypovolemia in subjects with intact autoregulation is associated with decreased microcirculatory diffusion (PVD) and convection (MFI and MFIhetero) properties and, consequently, decreased tissue oxygen carrying capacity (THI) and tissue oxygenation (StO2). Furthermore, using a VOT we found that resting tissue oxygen consumption was maintained under conditions of adequately compensated central hypovolemia.

‘Multi-associations’: predisposed to misinterpretation of peripheral tissue oxygenation and circulation in neonates

Interpretation of peripheral circulation in ill neonates is crucial but difficult. The aim was to analyse parameters potentially influencing peripheral oxygenation and circulation. In a prospective observational cohort study in 116 cardio-circulatory stable neonates, peripheral muscle near-infrared spectroscopy (NIRS) with venous occlusion was performed. Tissue oxygenation index (TOI), mixed venous oxygenation (SvO2), fractional oxygen extraction (FOE), fractional tissue oxygen extraction (FTOE), haemoglobin flow (Hbflow), oxygen delivery (DO2), oxygen consumption (VO2), and vascular resistance (VR) were assessed. Correlation coefficients between NIRS parameters and demographic parameters (gestational age, birth weight, age, actual weight, diameter of calf, subcutaneous adipose tissue), monitoring parameters (heart rate, arterial oxygen saturation (SaO2), mean blood pressure (MAP), core/peripheral temperature, central/peripheral capillary refill time) and laboratory parameters (haemoglobin concentration (Hb-blood), pCO2) were calculated. All demographic parameters except for Hbflow and DO2 correlated with NIRS parameters. Heart rate correlated with TOI, SvO2, VO2 and VR. SaO2 correlated with FOE/FTOE. MAP correlated with Hbflow, DO2, VO2 and VR. Core temperature correlated with FTOE. Peripheral temperature correlated with all NIRS parameters except VO2. Hb-blood correlated with FOE and VR. pCO2 levels correlated with TOI and SvO2. The presence of multiple interdependent factors associated with peripheral oxygenation and circulation highlights the difficulty in interpreting NIRS data. Nevertheless, these findings have to be taken into account when analysing peripheral oxygenation and circulation data.

Oxidative stress status in elite female volleyball athletes with depleted iron stores

BackgroundOxidative stress has been defined as a disturbance in the equilibrium status of pro-oxidant and antioxidant systems in favour of pro-oxidation. The elevated metabolic rate associated with exercise leads to...

Effect of adrenergic substances on oxygen consumption of rat brain tissue.

Effect of adrenergic substances on oxygen consumption of rat brain tissue.

Monitoring the microcirculation in the critically ill patient: reflectance spectroscopy

Dear Editor, I read with great interest and pleasure the excellent overview of the most common methods currently used to monitor the microcirculation by De Backer and colleagues [1]. The expertise of this group of authors with most of the methods described in their review of innumerable original publications was clearly evident. However, the section on reflectance spectroscopy is rather short, suggesting that they may lack in-depth practical experience with that specific method. In particular, the last sentence on recent developments in the technique is incorrect and needs to be explained more specifically. The first device using reflectance spectroscopy (EMPHO) was limited to perpendicular probes for mucosa measurements and was based on spectrophotometry only. Nevertheless, it has been used in numerous experimental and clinical studies performed by our group for assessing the effects of various factors and agents, such as positive airway pressure, intraabdominal pressure, hypercapnia, cardiopulmonary bypass, vasoactive drugs and anaesthetics, on the splanchnic microcirculation [for references, see the Electronic Supplementary Material (ESM)]. The latest development using reflectance spectroscopy is incorporated in the O2C (oxygen to see) device (Lea, Giessen, Germany). The technology of the O2C device is based on two physical principles: reflection spectroscopy and the laser Doppler technique. Compared to the EMPHO device, the O2C instrument integrates both techniques in a much smaller device because the rotating filter wheel has been replaced by a CCD-spectrometer and the xenon high-pressure lamp by a small light source optimised for fibre optics. Specific probes are used to introduce white light (wavelengths 500–800 nm) and laser light (wavelength 830 nm) simultaneously into the tissue. A part of the light spectrum is absorbed when the white light interacts with the erythrocytes, and this absorbed portion assumes the colour of the haemoglobin as a measure of its oxygen saturation. The laser light experiences a frequency displacement due to the moving erythrocytes (the so-called Doppler Shift), and this displacement is a measure of their velocity. The sum of all erythrocytes and their velocity is a measure of blood flow (volume flow) in the complex network of capillaries. With this device the following parameters can be measured simultaneously in tissue: the oxygen saturation of haemoglobin (μHbO2) at the venous end of the capillaries (the so-called “last meadow”); the regional amount of haemoglobin (rHb) in the micro-blood vessels as a measure of its blood volume and for capillary density; the velocity of the blood in microcirculation; the flow of blood in the microcirculation. The main advantage of this technology when assessing microvascular blood flow is that this combination of parameters allows the determination of regional oxygen consumption (rVO2) in the tissue as a direct measure of tissue viability. The metabolism may be a more important parameter than the heterogeneity of perfusion, which is considered to be a key to monitor sepsis (for details, see ESM). The method has been used clinically to assess the microvascular response in patients with septic shock [2], to monitor the effects of extreme anaemia [3] or flap viability [4] and to predict wound healing in burn injury [5]. In conclusion, the combination of reflection spectroscopy and laser Doppler (O2C) may offer a useful enlargement of the diagnostic tools available to the clinician for assessing microvascular blood flow and tissue oxygen consumption.

AN IMPROVED MODEL FOR THE DIFFUSION OF OXYGEN INTO RESPIRING WOOD

Diffusion is an essential component of gas exchange at the cellular and tissue level, and a mathematical analysis of diffusion is therefore important to model biological processes in many systems. When several factors affect diffusion, finding an explicit non-steady-state equation can be difficult or impossible. In an earlier work (J Biol Systems15:63–72), we described such a function for a system where oxygen diffuses from the air into a body that consumes oxygen, assuming that the exchange surface is flat. Here, an explicit solution is limited to the case where tissue oxygen consumption decreases linearly with oxygen concentration and reaches 0 only when all oxygen has been consumed. The objective of this article is the analysis of gas diffusion into a respiring tissue that is cylindrical, which applies to tree stems and is a more realistic approximation for many other organs. This approach differs from diffusion along a flat surface, resulting in formally completely different explicit solutions, and is more flexible allowing for different relationships between oxygen concentration and tissue oxygen consumption.

Oxygen gradients in the microcirculation

Early in the last century August Krogh embarked on a series of seminal studies to understand the connection between tissue metabolism and mechanisms by which the cardiovascular system supplied oxygen to meet those needs. Krogh recognized that oxygen was supplied from blood to the tissues by passive diffusion and that the most likely site for oxygen exchange was the capillary network. Studies of tissue oxygen consumption and diffusion coefficient, coupled with anatomical studies of capillarity in various tissues, led him to formulate a model of oxygen diffusion from a single capillary. Fifty years after the publication of this work, new methods were developed which allowed the direct measurement of oxygen in and around microvessels. These direct measurements have confirmed the predictions by Krogh and have led to extensions of his ideas resulting in our current understanding of oxygenation within the microcirculation. Developments during the last 40 years are reviewed, including studies of oxygen gradients in arterioles, capillaries, venules, microvessel wall and surrounding tissue. These measurements were made possible by the development and use of new methods to investigate oxygen in the microcirculation, so mention is made of oxygen microelectrodes, microspectrophotometry of haemoglobin and phosphorescence quenching microscopy. Our understanding of oxygen transport from the perspective of the microcirculation has gone from a consideration of oxygen gradients in capillaries and tissue to the realization that oxygen has the ability to diffuse from any microvessel to another location under the conditions that there exists a large enough PO(2) gradient and that the permeability for oxygen along the intervening pathway is sufficient.

In vivo mapping of tumor oxygen consumption using 19F MRI relaxometry

Recently, we have developed a new electron paramagnetic resonance (EPR) protocol in order to estimate tissue oxygen consumption in vivo. Because it is crucial to probe the heterogeneity of response in tumors, the aim of this study was to apply our protocol, together with (19)F MRI relaxometry, to the mapping of the oxygen consumption in tumors. The protocol includes the continuous measurement of tumor po(2) during the following respiratory challenge: (i) basal values during air breathing; (ii) increasing po(2) values during carbogen breathing until saturation of tissue with oxygen; (iii) switching back to air breathing. We have demonstrated previously using EPR oximetry that the kinetics of return to the basal value after oxygen saturation are mainly governed by tissue oxygen consumption. This challenge was applied in hyperthyroid mice (generated by chronic treatment with L-thyroxine) and control mice, as hyperthyroidism is known to dramatically affect the oxygen consumption rate of tumor cells. Our recently developed snapshot inversion recovery MRI fluorocarbon oximetry technique allowed the po(2) return kinetics to be measured with a high temporal resolution. The kinetic constants (i.e. oxygen consumption rates) were higher for tumors from hyperthyroid mice than from control mice, data that are consistent with our previous EPR study. The corresponding histograms of the (19)F MRI data showed that the kinetic constants displayed a shift to the right for the hyperthyroid group, indicating a higher oxygen consumption in these tumors. The color maps showed a large heterogeneity in terms of oxygen consumption rate within a tumor. In conclusion, (19)F MRI relaxometry allows the noninvasive mapping of the oxygen consumption in tumors. The ability to assess the heterogeneity of tumor response is critical in order to identify potential tumor regions that might be resistant to treatment and therefore produce a poor response to therapy.

Oxygenation of the human retina

Abstract Purpose Partial pressure of oxygen in the optic nerve and retina is regulated by the intraocular pressure and systemic blood pressure, the resistance in the blood vessels and oxygen consumption of the tissue. The PO2 is autoregulated and moderate changes in intraocular pressure, blood pressure or tissue oxygen consumption do not affect the retinal and optic nerve oxygen tension. Methods If the intraocular pressure is increased above 40 mmHg or the ocular perfusion pressure decreased below 50 mmHg the autoregulation is overwhelmed and the optic nerve becomes hypoxic. The levels of perfusion pressure that lead to optic nerve hypoxia in the laboratory correspond remarkably well to the levels that increase the risk of glaucomatous optic nerve atrophy in human glaucoma patients. Medical intervention can affect optic nerve PO2. Lowering the intraocular pressure tends to increase the optic nerve PO2, even though this effect may be masked by the autoregulation when the optic nerve PO2 and perfusion pressure is in the normal range. Results Carbonic anhydrase inhibitors increase retinal PO2 through a mechanism of vasodilatation and lowering of the intraocular pressure. Carbonic anhydrase inhibition reduces the removal of CO2 from the tissue and the CO2 accumulation induces vasodilatation resulting in increased blood flow and improved oxygen supply. This effect is inhibited by indomethacin but not other cyclo‐oxygenase inhibitors. Conclusion Carbonic anhydrase inhibitors increase retinal blood flow and increase oxygen delivery. Glaucoma drugs and glaucoma surgery lower intraocular pressure, increase ocular perfusion pressure and blood flow. Demand of oxygen by retinal cells may be reduced through apoptosis and tissue atrophy, as well as active destruction of tissue by laser photocoagulation.

Retinal blood vessel phenotyping in mice

Abstract Purpose In the retina there is a compromise between optimal visual function and optimal oxygenation. Retinal blood vessels have a relative sparse distribution and their size is small in order to minimise optical interference with the light path. Hence, the blood flow volume in the retina is relatively low. This fact, together with the high oxygen consumption of the retinal tissue, could facilitate the development of retinal hypoxia and subsequent retinopathy when the vascular bed is altered. Thus, the analysis of retinal blood vessel must be a crucial step during retinal phenotyping in mutant mice. Methods Different technologies and methods have been used in order to analyze structure, distribution and function of retinal blood vessels, among others: retinal digest preparations, retinal whole mount immunohistochemistry, transmission and scanning electron microscopy, fluorescein and Mercox vascular injections and scanner laser ophthalmoscopy. Results In our laboratory, morphological and topographic alterations of retinal blood vessels in Bmi1 and Sirt1 knockout mice, as well as in IGF‐1 and IL‐10 transgenic mice, have been observed and documented Conclusion The mouse genome is fully sequenced. 99% of the coding genes present in man are also present in mouse. Moreover, the majority of disease‐related genes have been conserved since the emergence of the bony fishes about 400 million years ago. These facts and the development during the last two decades of an extensive toolbox to study the functional effects of genetic variation in mice, make them the ideal model organism for the study of human eye diseases. In this sense, morphological and functional analyses of retinal blood vessel in mutant mice could help to understand vascular gene‐based mechanisms that lead to retinopathy

Numerical study of oxygen transport in a carotid bifurcation

This study investigates the oxygen mass transport in the region around the human carotid bifurcation, particularly addressing the effects of bifurcation geometry and pulsatile blood flow on the oxygen transport between the blood flow and artery wall tissue, coupled with the metabolic oxygen consumption and oxygen diffusion in the artery wall tissue. The temporal variations and spatial distributions of the oxygen tension are predicted quantitatively using a geometric model of the human carotid bifurcation and realistic blood flow waveforms. Results reveal that the flow separation at the outside wall of the sinus of the internal carotid artery (ICA) can markedly alter the flow pattern, oxygen tension and the oxygen wall flux. Results also clarify that the flow unsteadiness has a secondary effect on the oxygen tension inside the wall. The non-dimensional oxygen flux, the Sherwood number Sh, at the outside wall of the ICA sinus, takes markedly lower values of about 45 than at other sites because the rates of oxygen transport by the convective flow are reduced at the outside wall of the ICA sinus. The transverse distributions of the oxygen tension inside the artery wall show parabolic profiles having minima in the middle of the wall thickness, with the lowest value of 35 mmHg. These predicted distributions of the oxygen tension inside the wall closely resemble those obtained from experiments. The results demonstrate that hypoxic zones appear inside the artery walls at locations where atherosclerotic lesions are prone to develop.

Mathematical analysis of corneal oxygenation

Purpose: To develop a quasi steady state model for the time course concentration profile describing the oxygen diffusion and consumption in a multilayered corneal tissue and investigate the effect of various model parameters on the oxygen concentration for open and closed eyes. Method: A simple mathematical model for the oxygen transport in multilayered corneal tissue was developed using Fick’s law of diffusion and Michaelis-Menten kinetics of metabolism. A Crank-Nicoloson finite difference scheme of the equation describing the oxygen diffusion and consumption was written, in which spatial diffusive terms were approximated by central differences while the temporal terms were approximated by average of forward and backward time differences. A system of linear equations obtained from the Crank-Nicholoson finite differences schemes was solved by the Thomos Algorithm. Result: The model predict that oxygen tension without contact lens for an open and closed eye increases along the distance from the aqueous side in each of the layers and the partial pressure gradient in the stroma is higher than that in the epithelium and endothelium layers. It is also observed that the oxygen tension with contact lens in the steady and transient stares, in case of low oxygen permeability of lens decreases along the distance from the aqueous side to the stroma, whereas, at higher oxygen permeability of the lens it increases along the distance for open and closed eyes. Conclusion: Oxygen tension as observed in the cornea of an open eye with or without contact lens is higher than that in closed eye. Also at a high oxygen permeability of contact lens enhance the oxygen tension significantly than that of low oxygen permeability. Keywords: Oxygen transport, finite difference, metabolism, oxygen consumption, pressure gradient.

Alterations in Gene Expression After Induction of Profound Hypothermia for the Treatment of Lethal Hemorrhage

We have previously demonstrated that induction of profound hypothermia improves long-term survival in animal models of complex injuries/lethal hemorrhage. However, the precise mechanisms have not been well defined. The aim of this high-throughput study was to investigate the impact of profound hypothermia on gene expression profiles. Wistar-Kyoto rats underwent 40% blood volume arterial hemorrhage over 10 minutes and were randomized into two groups based on core body temperatures (n = 7 per group): hypothermia (H, 15 degrees C) and normothermia (N, 37 degrees C). Hypothermia was induced by infusing cold isotonic solution using a cardiopulmonary bypass (CPB) setup. After reaching target body temperature, low-flow state (CPB flow rate of 20 mL x kg x min) was maintained for 60 minutes. Hypothermic rats were rewarmed to baseline temperature, and all rats were resuscitated on CPB and monitored for 3 hours. The N group underwent identical CPB management. Sham rats (no hemorrhage and no instrumentation) were used as controls. Blood samples were collected serially, and hepatic tissues were harvested after 3 hours. Affymatrix Rat Gene 1.0 ST Array (27,342 genes, >700,000 probes) was used to determine gene expression profiles (n = 3 per group), which were further analyzed using GeneSpring (Agilent Technologies, Santa Clara, CA) and GenePattern (Broad Institute, Cambridge, MA) programs. Data were further queried using network analysis tools including Gene Ontology, and Ingenuity Pathway Analysis (Ingenuity Systems). Key findings were verified using real-time polymerase chain reaction and Western blots. Induction of hypothermia significantly (p < 0.05) decreased the magnitude of lactic acidosis and increased the survival rates (100% vs. 0% in normothermia group). Five hundred seventy-one of 23,000 genes had altered expression in response to the induction of hypothermia: 382 were up-regulated and 187 were down-regulated. Twelve key pathways were specifically modulated by hypothermia. Interleukin-6, interleukin-10, p38 mitogen-activated protein kinase (MAPK), nuclear factor kappa-light-chain-enhancer of activated B cells, glucocorticoids, and other signaling pathways involved with acute phase reactants were up-regulated. Multiple metabolic pathways were down- regulated. The largest change was in the peroxisome proliferator-activated receptor gamma gene that codes for a transcriptional coactivator, which in turn controls mitochondrial biogenesis, glycerolipid, and other metabolic pathways in the liver. Apoptotic cell death cascades were activated in response to blood loss (H and N groups), but multiple specific anti-apoptotic genes (baculoviral Inhibitor of apoptosis protein repeat-containing 3, BCL3L1, NFKB2) displayed an increased expression specifically in the hypothermia treated animals, suggesting an overall pro-survival phenotype. Profound hypothermia increases survival in a rodent model of hemorrhagic shock. In addition to decreasing tissue oxygen consumption, induction of hypothermia directly alters the expression profiles of key genes, with an overall up-regulation of pro-survival pathways and a down- regulation of metabolic pathways.

Intra-arterial tert-Butyl-Hydroperoxide Infusion Induces an Exacerbated Sensory Response in the Rat Hind Limb and is Associated with an Impaired Tissue Oxygen Uptake

The objective of this study was to investigate oxidative stress and oxygen extraction mechanisms in an animal model of continuous intra-arterial infusion of a free radical donor and in an in vitro model using isolated mitochondria. tert-Butyl-hydroperoxide (tert-BuOOH, 25 mM) was infused for 24 h in the left hind limb of rats to induce soft tissue damage (n = 8). After 7 days, we assessed local sensory response, tissue oxygen consumption, oxygen radicals, and antioxidant levels. In vitro mitochondrial function was measured after stimulation of isolated mitochondria of skeletal muscle cells with increasing doses of tert-BuOOH. tert-BuOOH infusion resulted in an increased skin temperature (p = 0.04), impaired function, and a significantly increased pain sensation (p = 0.03). Venous oxygen saturation levels (p = 0.01) and the antioxidant ceruloplasmin (p = 0.04) were increased. tert-BuOOH inhibited mitochondrial function in vitro. Induction of free radical formation in the rat hind limb results in an exacerbated sensory response and is associated with impaired oxygen extraction, which likely results from mitochondrial dysfunction caused by free radicals.

Simulation of metabolism‐perfusion matching in a heterogeneous microvascular network

Microvascular blood flow regulation involves multiple mechanisms designed to maintain adequate perfusion under conditions of varying metabolic demand. The impact of various regulatory factors on metabolism‐perfusion matching was assessed using a heterogeneous microvascular network model that accounted for myogenic, shear, and metabolic flow regulation. Estimates of oxygen extraction under control conditions were compared to an increase in tissue oxygen consumption in combination with a reduction in perfusion. For the values of parameters used, overall oxygen extraction was increased by a factor of 7.19 with a tenfold increase in consumption and a factor of 1.47 when perfusion was reduced by 50%. Combining increased consumption with decreased flow resulted in an increase in extraction by a factor of 9.20 compared to control, suggesting that network regulatory capacity remained intact under these conditions. This has significant implications for the optimization of metabolism‐perfusion matching, since impairment of flow regulation under conditions of increased consumption and decreased perfusion can lead to microvascular perfusion heterogeneity and cause organ failure in critically ill patients.

Activity, abundance, distribution and expression of Na+/K+-ATPase in the salt glands ofCrocodylus porosusfollowing chronic saltwater acclimation

Saltwater crocodiles, Crocodylus porosus, possess lingual salt glands which function to remove excess Na(+) and Cl(-) accumulated as a consequence of living in salt water. Little is known about the nature of ion transport systems in C. porosus salt glands and how these systems respond to an osmotic challenge. In the present study, we examined the distribution and regulation of the Na(+)/K(+)-ATPase (NKA) pump, specifically the alpha-(catalytic) subunit in the salt glands of C. porosus chronically acclimated (6 months) to freshwater (FW) or 70% seawater (SW). We hypothesised that in the SW-acclimated C. porosus there would be an up-regulation of the abundance, activity and gene expression of the NKA transporter. NKA was immunolocalised to the lateral and basal membrane of secretory cells. As predicted, the NKA alpha-subunit was 2-fold more abundant in SW-acclimated C. porosus salt glands. NKA gene expression was also elevated in the salt glands of SW- vs FW-acclimated crocodiles. There was no increase in the specific activity of NKA in SW-acclimated animals and the in vitro rate of oxygen consumption by salt gland slices from SW-acclimated animals was not significantly different from that of FW-acclimated animals. The proportion of tissue oxygen consumption rate attributable to NKA activity was not different between SW- and FW-acclimated animals (approximately 50%). These data suggest that either chronic SW acclimation does not affect NKA in crocodile salt glands in the same manner as seen in other models or crocodiles possess the capacity to moderate NKA activity following prolonged exposure to SW.

Quantification of the effects of vasomotion on mass transport to tissue from axisymmetric blood vessels

The process known as vasomotion, rhythmic oscillations in vessel diameter, has been proposed to act as a protective mechanism for tissue under conditions of reduced perfusion, since it is frequently only observed experimentally when perfusion levels are reduced. This could be due to a resultant increase in oxygen transport from the vasculature to the surrounding tissue, either directly or indirectly. It is thus potentially of significant clinical interest as a warning signal for ischemia. However, there has been little analysis performed to quantify the effects of vessel wall movement on time-averaged mass transport. We thus present a detailed analysis of such mass transport for an axisymmetric vessel with a periodically oscillating wall, by solving the non-linear mass transport equation, and quantify the differences between the time-averaged mass transport under conditions of no oscillation (i.e. the steady-state) and varying wall oscillation amplitude. The results show that if the vessel wall alone is oscillated, with an invariant wall concentration, the time-averaged mass transport is reduced relative to the steady-state, but if the vessel wall concentration is also oscillated, then mass transport is increased, although this is generally only true when these oscillate in phase with each other. The influence of Péclet number and the non-dimensional rate of consumption of oxygen in tissue, as well as the amplitude of oscillations, are fully characterised. We conclude by considering the likely implications of these results in the context of oxygen transport to tissue.

Effects of the Oral Administration of a β3-Adrenergic Agonist on Lipid Metabolism in Alloxan-Diabetic Rats

Previous studies have reported that beta3-adrenergic agonists regulate plasma glucose, triglycerides and free fatty acids in situations of hyperglycaemia and dyslipidaemia in rodents. In this study Trecadrine, a novel compound with affinity for beta3-adrenergic receptors, has been tested in an alloxan-induced model of hyperglycaemia in rats. Alloxan-induced hyperglycaemic rats were orally treated with Trecadrine (1 mg/kg/day for 4 days), resulting in an improvement of hyperglycaemia (from 16.6 to 8.3 mmol L(-1), P < 0.001). This effect was not associated with statistical differences in plasma insulin levels, which may be explained by changes in insulin resistance and carbohydrate oxidation in peripheral tissues. Furthermore, a reduction in internal white fat weight (-39%), which was not statistically significant, as well as in plasma triglycerides (from 1.89 to 0.33 mmol L(-1), P < 0.001) and free fatty acids (from 0.70 to 0.39 mmol L(-1), P < 0.001), was found after Trecadrine administration. Trecadrine apparently induced lipolytic activity in adipocytes, as suggested by the increase of oxygen consumption in white adipose tissue (+282%, P < 0.001), while free fatty acids decreased apparently through their utilisation in other tissues. Furthermore, the increase in brown adipose tissue oxygen consumption (+50%, P < 0.01) and in rectal temperature (P < 0.05) suggests that both glucose and fatty acid oxidation may be enhanced in this tissue. These results give support to the possible therapeutic use of beta3-adrenergic compounds in situations of hyperglycaemia, particularly when this is accompanied by hypertriglyceridaemia.

Effect of phenol on oxygen consumption and bioaccumulation in different tissues of freshwater fish Cyprinus carpio

The influence of phenol exposure history on the rates of phenol accumulation, elimination, and oxygen consumption was examined in the fresh water fish species Cyprinus carpio. Bioaccumulation and elimination of phenol from the kidney and biochemical parameters of liver gill and muscle were determined at intervals of 10, 20, and 30 days. A significant increase in phenol concentration was noted in all treated groups. The acute toxicity of phenol was 30.0 mg/L. Changes were dose and duration dependant when fish were exposed for 30 days to two sublethal concentrations of phenol (1.5 and 3.0 mg/L). Recovery post exposure was observed after transfer to normal tap water for 30 days. Elimination of phenol was noted, although the concentration remained significantly higher than the control. The longer the phenol exposure time, the greater was the percentage reduction of organic matter of the fish. Total protein, total carbohydrate, and total lipids in the tissues of liver, gill, and muscle decreased significantly. On the other hand, these parameters were higher at the end of the experiment than at the start (ANOVA P < or = .01).

Local maximum oxygen disappearance rate has limited utility as a measure of local renal tissue oxygen consumption

Introduction: Methods for measurement of local oxygen consumption (VO 2) are required to allow development of treatments for kidney disease that target kidney oxygen dysregulation. In anaesthetized rabbits, we determined whether local oxygen disappearance rate (ODR) during complete renal ischaemia reflects tissue VO 2 in the kidney and in hindlimb skeletal muscle (biceps femoris). Methods: Whole kidney VO 2 was determined under conditions employed to alter oxygen consumption. The ureter was ligated to reduce VO 2 ( n = 6) or the mitochondrial uncoupler 2,4-dinitrophenol was administered to increase VO 2 ( n = 6). An additional 10 rabbits were studied which received neither treatment. Immediately following VO 2 measurements, oxygen partial pressure (PO 2) was measured, over the first 60 s after abrupt cardiac arrest, using fluorescence optodes and in a subset of experiments ( n = 6), Clark electrodes. Parallel experiments were performed in hindlimb skeletal muscle (biceps femoris). Results: ODR in the renal cortex and medulla, and in biceps femoris, was linear during the first ∼ 15 s after cardiac arrest ( r 2 ≈ 0.98). Using fluorescence optodes, maximum ODR averaged across all 22 rabbits in which the kidney was studied was − 0.75 ± 0.09 and − 0.60 ± 0.06 mm Hg/s respectively in the renal cortex and medulla. Maximum ODR averaged across all 10 rabbits in which the biceps femoris was studied was − 0.30 ± 0.06 mm Hg/s. ODR increased at greater initial PO 2 only in the renal cortex. ODR in neither the renal medulla nor biceps femoris varied with whole organ VO 2, although renal cortical ODR normalized for initial PO 2 was significantly correlated with whole organ VO 2 ( r 2 = 0.19). Maximum ODR obtained by Clark electrode was approximately four-fold greater than that obtained by fluorescence optode. Discussion: Because ODR correlates poorly with whole organ VO 2, it likely has limited utility as a measure of local VO 2.