Changes In Oxygen Utilization Research Articles

Visualization of the consequences of Succinate Dehydrogenase Inhibition on Oxygen utilization During Hemorrhagic Shock using Hyperspectral Imaging

IntroductionHemorrhagic shock (HS) results in reduced pressure, limited blood flow, and inadequate oxygen delivery to maintain cellular function. Reduced microcirculatory blood flow results in ischemia, as the tissue is no longer properly perfused or oxygenated. During resuscitation from HS, reperfusion promotes the formation of reactive oxygen species (ROS) as a byproduct of the Krebs cycle. Itaconate limits formation of ROS generated during reperfusion by inhibiting succinate dehydrogenase (SDH) activity, thus limiting tissue and organ damage. Hyperspectral Imaging (HSI) can be used to interrogate hemoglobin oxygen (HbO2) saturation in microvessels. Thus, the objective of this study was to use HSI to monitor changes in oxygen utilization within the microcirculation during resuscitation from HS with itaconate pretreatment.Materials and MethodsGolden Syrian hamsters were instrumented with a dorsal window chamber. A Resonon Pika‐L (Resonon, Bozeman, MT, USA) bench top HSI system was used. Each image was fitted with a Spatial mean filter and Savitzky‐Golay filter to decrease scatter noise, and a vessel mask was applied based on an intensity threshold to remove tissue from blood vessels. Spectral rescaling and a linear least squares fit were used to provide abundance of Hb and HbO2. Hemorrhage was induced by withdrawing 50% of the animal’s blood volume (BV, estimated as 7% of body weight) over 10 minutes. During hemorrhage and shock, images were taken continuously using a custom Python algorithm controlling the camera and illumination with a custom build relay. Before fluid resuscitation, itaconate was administered. Fluid resuscitation was accomplished by infusion of 25% of the animal’s BV of HEXTEND® (6% Hetastarch in Lactated Electrolyte Injection. Hospira Inc, Lake Forest, IL). The animal was resuscitated over 10 minutes and images taken every minute. Recovery was monitored over a period of 1 hour with images taken every 5 minutes.Results and DiscussionIncreasing doses of itaconate restored HbO2 saturation in venules, which confirms the inhibition of SDH by itaconate. Itaconate limits oxygen consumption of the tissues, preventing the formation of ROS in tissue during reperfusion, as indicated by higher levels of venular O2 saturation. However, these effects are only temporary as the HbO2 saturation levels taper off over time.ConclusionsIn conclusion, the inhibition of SDH with itaconate lead to the accumulation of succinate, limited tissue oxygen utilization, and prevented the formation of ROS during reperfusion. With further research, itaconate could potentially help to reduce reperfusion sequalae post treatment of trauma injuries, surgery, and combat casualties. In future studies, we aim to administer itaconate as an additive to the resuscitation fluid with the goal of evaluating the long‐term implications of preventing reperfusion injury.Support or Funding InformationThis study was supported by NIH NHLBI R01HL126945 and R01HL138116.

The Effect of Short and Long Term Endurance Training on Systemic, and Muscle and Prefrontal Cortex Tissue Oxygen Utilisation in 40 - 60 Year Old Women.

PurposeAerobic endurance training (ET) increases systemic and peripheral oxygen utilisation over time, the adaptation pattern not being linear. However, the timing and mechanisms of changes in oxygen utilisation, associated with training beyond one year are not known. This study tested the hypothesis that in women aged 40–60 years performing the same current training load; systemic O2 utilisation (VO2) and tissue deoxyhaemoglobin (HHb) in the Vastus Lateralis (VL) and Gastrocnemius (GAST) would be higher in long term trained (LTT; > 5 yr) compared to a short term trained (STT; 6–24 months) participants during ramp incremental (RI) cycling, but similar during square-wave constant load (SWCL) cycling performed at the same relative intensity (below ventilatory turn point [VTP]); and that pre-frontal cortex (PFC) HHb would be similar between participant groups in both exercise conditions.MethodsThirteen STT and 13 LTT participants performed RI and SWCL conditions on separate days. VO2, and VL, GAST, and PFC HHb were measured simultaneously.ResultsVO2peak was higher in LTT compared to STT, and VO2 was higher in LTT at each relative intensities of 25%, 80% and 90% of VTP in SWCL. HHb in the VL was significantly higher in LTT compared to STT at peak exercise (4.54 ± 3.82 vs 1.55 ± 2.33 μM), and at 25% (0.99 ± 1.43 vs 0.04 ± 0.96 μM), 80% (3.19 ± 2.93 vs 1.14 ± 1.82 μM) and 90% (4.62 ± 3.12 vs 2.07 ± 2.49 μM) of VTP in SWCL.ConclusionsThe additional (12.9 ± 9.3) years of ET in LTT, resulted in higher VO2, and HHb in the VL at peak exercise, and sub—VTP exercise. These results indicate that in women 40–60 years old, systemic and muscle O2 utilisation continues to improve with ET beyond two years.

The Effect of Active versus Passive Recovery Periods during High Intensity Intermittent Exercise on Local Tissue Oxygenation in 18 - 30 Year Old Sedentary Men.

PurposeHigh intensity interval training (HIIT) has been proposed as a time-efficient format of exercise to reduce the chronic disease burden associated with sedentary behaviour. Changes in oxygen utilisation at the local tissue level during an acute session of HIIT could be the primary stimulus for the health benefits associated with this format of exercise. The recovery periods of HIIT effect the physiological responses that occur during the session. It was hypothesised that in sedentary individuals, local and systemic oxygen utilisation would be higher during HIIT interspersed with active recovery periods, when compared to passive recovery periods.MethodsTwelve sedentary males (mean ± SD; age 23 ± 3 yr) completed three conditions on a cycle ergometer: 1) HIIT with passive recovery periods between four bouts (HIITPASS) 2) HIIT with active recovery periods between four bouts (HIITACT) 3) HIITACT with four HIIT bouts replaced with passive periods (REC). Deoxygenated haemoglobin (HHb) in the vastus lateralis (VL) and gastrocnemius (GN) muscles and the pre-frontal cortex (FH), oxygen consumption (VO2), power output and heart rate (HR) were measured continuously during the three conditions.ResultsThere was a significant increase in HHb at VL during bouts 2 (p = 0.017), 3 (p = 0.035) and 4 (p = 0.035) in HIITACT, compared to HIITPASS. Mean power output was significantly lower in HIITACT, compared to HIITPASS (p < 0.001). There was a significant main effect for site in both HIITPASS (p = 0.029) and HIITACT (p = 0.005). There were no significant differences in VO2 and HR between HIITPASS and HIITACT.ConclusionsThe increase in HHb at VL and the lower mean power output during HIITACT could indicate that a higher level of deoxygenation contributes to decreased mechanical power in sedentary participants. The significant differences in HHb between sites indicates the specificity of oxygen utilisation.

Adaptation of local muscle blood flow and surface electromyography to repeated bouts of eccentric exercise.

The aim of this randomized controlled crossover study was to investigate the effect of a bout of unaccustomed eccentric exercise (ECC) followed by a consecutive bout of the same intensity on local muscle blood flow, amplitude, and frequency of the electromyographic (EMG) signal from the exercised tibialis anterior muscle. Sixteen healthy male participants (age, 25.7 (0.6) years; body mass index 24.8 (1) kg·m(-2) participated in this study. Two identical bouts of high-intensity ECC were performed on the tibialis anterior muscle 7 days apart. Control sessions involving no exercise were performed 4 weeks either before or after the exercise sessions. Changes in local total blood flow [ΔtHb], EMG root mean square, and median power frequency were recorded during isometric maximum voluntary contraction of ankle dorsiflexion. Measurements were performed before, immediately after, and the day after both ECCs (ECC1 and ECC2). The participants rested quietly in a chair in the control session. Eccentric exercise 1 led to a significant decrease in [ΔtHb] on the day after (p ≤ 0.05), whereas ECC2 did not. Median power frequency decreased significantly in ECC2 compared with ECC1 (p < 0.01). Root mean square was unchanged in all the instants. The present study showed that adaptation is depicted in the local muscle blood flow and the frequency contents of the EMG after an unaccustomed ECC inducing muscle soreness. These alterations provide a potential mechanism for a rapid adaptation, which decreases susceptibility of the muscle to develop further soreness in the subsequent ECC bout.

Organ Failure in the ICU: Cellular Alterations

The physiological and biochemical abnormalities that constitute multiple organ failure represent cellular perturbations that, importantly, need to be reconciled with a lack of significant cell death together with availability but impaired utilization of oxygen. In conjunction with the relatively rapid ability of the organ to recover in surviving patients, a paradigm of metabolic shutdown triggered by a decrease in mitochondrial energy production appears increasingly valid. This review discusses data demonstrating temporal changes in oxygen utilization through the septic process, evidence for mitochondrial derangements, and recovery of mitochondrial function preceding clinical recovery.

Measurement of cerebral perfusion with arterial spin labeling: Part 1. Methods

Arterial spin labeling (ASL) is a magnetic resonance imaging (MRI) method that provides a highly repeatable quantitative measure of cerebral blood flow (CBF). As compared to the more commonly used blood oxygenation level dependent (BOLD) contrast-based methods, ASL techniques measure a more biologically specific correlate of neural activity, with the potential for more accurate estimation of the location and magnitude of neural function. Recent advances in acquisition and analysis methods have improved the somewhat limited sensitivity of ASL to perfusion changes associated with neural activity. In addition, ASL perfusion measures are insensitive to the low-frequency fluctuations commonly observed in BOLD experiments and can make use of imaging sequences that are less sensitive than BOLD contrast to signal loss caused by magnetic susceptibility effects. ASL measures of perfusion can aid in the interpretation of the BOLD signal change and, when combined with BOLD, can measure the change in oxygen utilization accompanying changes in behavioral state. Whether used alone to probe neural activity or in combination with BOLD techniques, ASL methods are contributing to the field's understanding of healthy and disordered brain function.

Human brain glucose metabolism may evolve during activation: Findings from a modified FDG PET paradigm

In human brain, short-term physiological stimulation results in dramatic and proportional increase in blood flow and metabolic rate of glucose but minimal change in oxygen utilization, however, with continuing stimulation, we have observed that blood flow response diminishes and oxygen utilization increases. Given the temporal limitation of conventional methods to measure glucose metabolism in the human brain, we modified [18F]fluorodeoxyglucose (FDG) PET paradigm to evaluate the short-term and long-term effects of visual stimulation on human brain glucose metabolism. In the present study, seven healthy volunteers each underwent three dynamic FDG PET studies: at rest and after 1 min and 15 min of visual stimulation (using reversing black–white checkerboard) which continued for only 5 min after FDG injection. We found that increase in FDG uptake in the visual cortex was attenuated by 28% when preceded by 15 min of continuous visual stimulation (p<0.001). This decline in metabolism occurred in the absence of any behavior changes in task performance. The similarity in behavior of blood flow and glucose metabolism over time supports the hypothesis that, in activated brain, blood flow is modulated by changes in cytosolic free NADH/NAD+ ratio related to increased glycolysis. Furthermore, the observed decline in glucose metabolism may reflect a shift from glycolytic to oxidative glucose metabolism with continued activation.

Complement C5 and Early Oxygen Kinetics during Murine Sepsis

Changes in oxygen consumption (VO(2)) and carbon dioxide production (VCO(2)) are common but poorly understood features of sepsis. The authors studied the role of complement C5 in the development of abnormal oxygen kinetics during sepsis in mice, arguing that as a pro-inflammatory event, complement activation might exacerbate disturbances in oxygen use during abdominal sepsis. An open-circuit indirect calorimeter was used to measure VO(2), VCO(2), and respiratory exchange ratio during a seven-day median lethal dose (LD(50)) murine cecal ligation and puncture (CLP) model. CLP produced significant changes in oxygen kinetics within three hours of onset, although when the animals were stratified by seven-day survival, no difference in these abnormalities was seen between the survivors and the nonsurvivors. Genetic deficiency of C5 did not ameliorate the changes in oxygen utilization. Rather, the C5-deficient mice experienced more severe abnormalities in oxygen kinetics and greater mortality. Treating animals with anti-C5a antibodies at the time of injury had little effect on oxygen kinetics, indicating that C5b, rather than C5a, was predominantly acting to protect the mice during the first 24 hours of illness. These findings indicate that the primary contribution of C5 to oxygen kinetics during sepsis is salutary through the host defense conveyed by generation of C5b, rather than detrimental by worsening oxygen utilization via pro-inflammatory mechanisms.

A Comparison of Accelerometers for Predicting Energy Expenditure and Vertical Ground Reaction Force in School-Age Children

In this pilot study of 16 children, we evaluated the reliability and validity of three accelerometers (Mini-Motionlogger [MML], Computer Science Applications, Inc. Actigraph [CSA], and BioTrainer) as indicators of energy expenditure and vertical ground reaction force. The children wore 2 of each type of monitor while they walked, ran, and performed 2 jumping tasks on a force plate and walked, jogged, and ran on a treadmill. Intrainstrument reliability of the monitors ranged from .64 to .98 across the treadmill tasks and from .69 to .98 across the force plate tasks, with the MML and CSA appearing more consistent than the BioTrainer. Analyses of variance were conducted to compare activity counts with criterion measures (oxygen utilization and force plate scores). All of the monitors generally differentiated among the treadmill tasks, mirroring the change in oxygen utilization. The CSA monitors corresponded more closely to the changes in force plate scores than the BioTrainer or the MML. Simple regression analyses indicated that count scores from all of the monitors were associated with oxygen utilization, with the MML and CSA exhibiting stronger relations (R values = .81 and .83, respectively) than the BioTrainer (R= .60). Similar analyses between the activity monitors and the force plate scores were also significant but the relations were not as strong as for oxygen utilization (R values = .46, .51, and .52, respectively). Based on backward elimination regression analyses, caloric expenditure on the treadmill tasks was predicted significantly with each of the MML (37 and 38% of variance) and CSA (39 and 42% of variance) units when body mass was included in the model. For the BioTrainer counts to provide the best prediction of caloric expenditure, both body mass and height were retained in the model, resulting in 20 and 25% explained variance. Future research to evaluate the utility of accelerometers should employ tasks that prevent the confounding of force and caloric expenditure.

Investigation of the initial dip in fMRI at 7 Tesla.

In agreement with optical imaging studies, previous fMRI studies have reported an initial decrease (i.e. the initial dip) in the BOLD response, which is believed to arise from an increase in oxygen consumption and to be mostly microvascular. To date, experimental studies of the initial dip in humans have been performed at fields up to 4 T, with relatively low spatial resolution. Because the sensitivity to microvascular contribution is increased at high magnetic fields, the present study investigated the initial dip at 7 T. In addition, to reduce the partial volume effect, the study is conducted at a high spatial resolution. The initial dip was detected in all subjects studied and was found to reside mostly in the gray matter. The relative amplitude of the early response was found to be 0.6, higher than that at 4 T (0.3) and 1.5 T (0.11). In addition, based on the assumption that the initial dip is a result of increased oxygen utilization, the fractional change in oxygen utilization was estimated to be 40% of that of the fractional change in cerebral blood flow. These results are in agreement with the notion that the initial dip arises from an increase in oxygen consumption.

Differential alterations in systemic and regional oxygen delivery and consumption during the early and late stages of sepsis.

Studies have indicated that regional changes in oxygen utilization during sepsis cannot be predicted from the changes in the whole body oxygen delivery (DO2) and consumption (VO2). The aim of this study, therefore, was to determine whether differential alterations in systemic and regional DO2 and VO2 occur during the early and late stages of sepsis. Adult male Sprague-Dawley rats were subjected to sepsis by cecal ligation and puncture (CLP). At 5 hours (i.e., the early, hyperdynamic phase of sepsis) or 20 hours (i.e., the late, hypodynamic phase) after CLP, cardiac output, and organ blood flow were measured by radioactive microspheres. Systemic and regional DO2 and VO2 were determined and plasma levels of lactate were measured. Cardiac output and blood flow to the liver, small intestine, and kidneys increased at 5 hours and decreased at 20 hours after CLP. Although both systemic DO2 and VO2 increased at 5 hours after CLP, systemic DO2 but not VO2 decreased at 20 hours. At 5 hours after CLP, intestinal and renal DO2 increased. However, DO2 in all the tested organs decreased at 20 hours after CLP. VO2 increased in the liver, small intestine, and kidneys at 5 hours after CLP but decreased only in the liver and small intestine at 20 hours after the onset of sepsis. Moreover, plasma lactate levels increased at the late stage of sepsis. Because hepatic and intestinal VO2 but not systemic and renal VO2 decreased at 20 hours after CLP, the liver and small intestine seem to be more vulnerable to the hypoxic insult during the hypodynamic stage of polymicrobial sepsis.

Reflex sympathetic activation induces acute insulin resistance in the human forearm.

Inferences about the association between sympathetic overactivity and insulin resistance have been drawn from the infusion of sympathomimetic amines in supraphysiological doses. We used the isolated perfused human forearm to investigate the effect of reflex-induced sympathetic nervous system activation on the peripheral utilization of glucose in the skeletal muscles of 14 healthy men. Local hyperinsulinemia in the forearm (132 +/- 25 microunits/mL for 90 minutes) induced a significant increase in the utilization of glucose from baseline (16.4 +/- 3.1 mg.dL-1.min-1 per 100 mL forearm volume) to a plateau (85.7 +/- 15.1 mg.dL-1.min-1 per 100 mL forearm volume) between 40 and 60 minutes of insulin infusion but did not alter the utilization of oxygen. Reflex sympathetic nervous system activation was elicited by unloading of cardiopulmonary receptors with bilateral thigh cuff inflation to 40 mm Hg between 60 and 90 minutes of insulin infusion. Blood flow in the forearm was significantly decreased with inflation of thigh cuffs (average decrease of 19%, p < 0.0001). As a result of thigh cuff inflation, there was a reduction in the utilization of glucose (a decrease of 23%, p < 0.02), whereas oxygen utilization was unchanged. We find that an increase in sympathetic nervous system activation (within the normal range of physiological responses) can cause acute insulin resistance in the forearm of healthy volunteers. The reflex caused no change in oxygen utilization, but the same stimulus elicited a decrease in the utilization of glucose.(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of nicardipine on rest and exercise hemodynamics in chronic congestive heart failure

The hemodynamic response to vasodilation induced by the new calcium channel antagonist nicardipine was studied in 10 patients with severe, chronic congestive heart failure. Rest and exercise hemodynamics were evaluated in the baseline state and after 1 week of oral nicardipine therapy (30 mg 3 times daily). In addition, respiratory gas exchange and arteriovenous oxygen difference were measured to assess changes in oxygen utilization. The responses of the sympathetic nervous system were evaluated by measuring plasma norepinephrine concentrations at rest and during maximal exercise. At rest, nicardipine administration was associated with significant reductions in mean systemic arterial pressure, systemic vascular resistance, pulmonary artery wedge pressure and pulmonary arterial pressure, and significant increases in cardiac index and stroke volume index. These effects were maintained during exercise. In contrast to findings with other calcium channel antagonists, no negative inotropic effect of nicardipine was identified. Nicardipine administration was associated with reduction of arteriovenous oxygen difference. Nicardipine had no effect on plasma norepinephrine concentrations, suggesting absence of reflex sympathetic nervous activation. Thus, nicardipine-mediated vasodilation leads to significant improvements in both rest and exercise cardiac performance.

Hepatic mitochondrial and microsomal recovery of rats intoxicated with CCl4.

The hepatic mitochondrial and microsomal recovery of rats intoxicated with CCl4 was investigated with specific reference to the oxygen utilization of liver slices. In control rats, the major oxygen utilization of the liver slices was at-tributed to mitochondrial particles. Since the mitochondrial oxygen utilization was inhibited by cyanide, the microsomal oxygen utilization was induced by NADPH and phenobarbital (a substrate for microsomal mixed function oxidase). Changes in oxygen utilization were observed in the recovery course of rats intoxicated with CCl4, and the recovery of mitochondria was found to be faster than that of micro-somes. A sex difference was present in the recovery mechanism of the microsomes.

Age-related changes in oxygen consumption by guinea pig paramedian cortex

Oxygen consumption by the paramedian cortex was measured in guinea pigs between 2 days of age and adulthood (i.e. > 50 days old) in an oxygen metabolic chamber in order to asses the age-related changes in oxygen metabolism in the developing brain. Brain slices of 2–10-day-old neonates exhibited the highest rate of oxygen utilization, with aging cortex exhibiting a linear decrease in oxygen metabolism. A plateau in oxygen utilization occurred between 40 and 50 days of age which was maintained throughout adulthood. These data indicate that the cortex of the guinea pig neonate demands a greater oxygen supply than that of the adult animal, which suggests that metabolic changes in oxygen utilization are developmentally related in the brain of the guinea pig.

Blunt Cardiac Trauma

Cardiac mitochondria showed significant uncoupling of oxidative phosphorylation after rats were given intraperitoneal alcohol. The rate of oxygen utilization in the absence of ADP was increased while there was no significant change in oxygen utilization in the presence of ADP. These in vivo results were confirmed with in vitro experiments. Also, intraperitoneal alcohol increased the mortality of blunt cardiac trauma. The alterations in cardiac energy metabolism demonstrated may explain the increased mortality in alcohol-pretreated animals subjected to cardiac contusion.

A comparative study of the respiratory responses of the bivalves Arctica islandica (L.) and Mytilus edulis L. to declining oxygen tension

The bivalves Arctica islandica and Mytilus edulis generally maintain respiratory independence during hypoxia, but the mechanisms by which this is achieved are very different. In declining oxygen tension, Arctica increases the rate of ventilation down to a low P O 2 of about 7 kPa, while oxygen utilization is gradually reduced. In contrast, Mytilus shows only a slight initial increase in ventilation rate, which then falls steadily as the P O 2 of the medium declines, while the oxygen utilization increases sharply. Mytilus which have lost the ability to maintain respiratory independence show little change in oxygen utilization. The increase in ventilation rate of the subtidal Arctica is brought about principally by increasing the duration of the pumping periods, a mechanism not available to Mytilus which, like other intertidal species studied, normally pumps more or less continuously whenever it is immersed. The cardiac responses to hypoxia are very similar in both Arctica and Mytilus ; heart rate and amplitude increase down to a P O 2 of about 2-4 kPa, below which both decrease rapidly. In Arctica the ventilation/perfusion ratio remains approximately constant over the range of oxygen tension that respiratory independence is maintained. In Mytilus this ratio gradually declines as the ambient P O 2 is reduced. It is suggested that the different respiratory responses to hypoxia of these two species may be due to the different patterns of pumping behaviour related to their different habitats, and to the relative energy costs of pumping blood and water.

Evaluation of Opercular Catheterization as a Method for Sampling Water Expired by Fish

Experiments were carried out on rainbow trout to see if cannulae implanted at different positions on the operculum yield accurate estimates of mean expired oxygen tension. This value is frequently used to calculate utilization or ventilation volume in fish and should therefore be accurately determined.Opercular oxygen tension [Formula: see text] recorded from seven quiescent fish (383–426 g, 10–12 C) in aquaria was highly variable with respect to time and cannula placement. Expired [Formula: see text] recorded from cannulae placed in the middle, upper, or lower part of the posterior margin of the operculum ranged from 54 to 157 mm Hg and was sometimes identical with inspired [Formula: see text]. When the fish were chased, expired oxygen tension usually rose but the magnitude of the rise and its duration were not uniform from cannula placement to placement. Other studies, on 21 trout (217–388 g, 10–12.5 C) whose gills were perfused with water at different flow rates with a mouth tube, indicated that the [Formula: see text] variability existed over a wide range of perfusion rates. In addition, [Formula: see text] levels from all three placements at perfusion rates approximating those of normal ventilation were frequently below the mean expired oxygen tension calculated from oxygen uptake and gill water-flow rate data.It is concluded that opercular cannulae provide poor estimates of mean expired oxygen tension in trout. The use of this technique to determine mean [Formula: see text] could lead to serious errors. It appears that large changes in oxygen utilization can be detected with opercular cannulae but any utilization values determined in this way would likely be erroneous.

Flow-through polarographic respirometry for aquatic animals

A polarographic method of measuring oxygen consumption of aquatic animals, which is based upon expanding the input signal to a potentiometric recorder, has been described. This gives a magnified visual tracing that can be measured with the polar planimeter and related proportionately to the oxygen concentration to accurately measure the metabolism of aquatic animals with wet body weights of 5 mg or more. Changes in oxygen utilization of 0.04 per cent concentration of oxygen are readily visible, and results are reproducible.

Oxygen tension of peripheral tissue

Changes in oxygen tension of living tissues in situ can be estimated by means of a small platinum electrode in a suitable electrical circuit. Many such studies have been made in normal human extremities, in which during cutaneous vasodilatation the cutaneous oxygen tension closely approaches that of arterial blood. In cutaneous vasoconstriction and with arterial occlusion the oxygen tension of the skin is reduced, sometimes to a small fraction of that in normal vasodilated skin. In ischemic extremities cutaneous oxygen tension can be increased by environmental oxygen, by inhaled oxygen and by various physical measures and drugs that increase the cutaneous circulation. There is some evidence that cutaneous oxygen tension can be made to change without concomitant changes in blood flow, perhaps because of changes in oxygen utilization or in the rate of delivery of oxygen through the capillary wall. Fewer studies have been made on oxygen tension of muscle: these have been of resting skeletal muscle. In normal man oxygen tension of muscle rises when oxygen is inhaled and decreases with arterial arrest by a pressure cuff. Changes in oxygen tension of muscle with positional changes have also been demonstrated. The several drugs studied produced no measurable change in oxygen tension of human muscle. In the dog epinephrine appears to increase the oxygen tension of muscle. Oxygen tension tends to reflect blood flow but the method measures the resultant of oxygen delivered through capillaries and utilized by the tissue rather than the total blood flow alone. More measurements, perhaps especially those of muscle, are needed in studies of the complex disorders incident to peripheral vascular disease.