Cardio-respiratory effects of chloramine-T exposure in rainbow trout

In order to establish whether the blood gas respiratory disturbances noted with exposure to chloramine-T are due to differences in the rates of uptake of O₂ and excretion of CO₂ or gill blood flow, adult rainbow trout (Oncorhynchus mykiss) were fitted with dorsal aorta and bulbus arteriosus catheters to facilitate blood pressure recordings, an ultrasonic blood flow probe and opercular impedance electrodes. Fish received either a 45-min static exposure to 9 mg l⁻¹ chloramine-T or tap water (control) and continuous recordings of blood pressure, and ventilation frequency and amplitude were made. Pre- and post-exposure arterial and venous blood samples were taken and analyzed for O₂ and CO₂ content, hemoglobin concentration and hematocrit. Chloramine-T exposure had no effect on any of the continuously recorded parameters. However, individual measurements (made immediately prior to and following exposure) of cardiac output and O₂ uptake rates increased significantly following exposure to chloramine-T compared to before exposure. CO₂ excretion rates were unaffected by chloramine-T exposure. Calculation of the perfusion convection requirement showed a significant increase for CO₂ but not for O₂. It was concluded that increases in O₂ uptake resulted from increased cardiac output but that CO₂ excretion, a diffusion-limited process, was not increased due to additional diffusive limitations caused by the irritant effect of chloramine-T.     

Detection of hydrogen peroxide production in the isolated rat lung using Amplex red

Abstract

The objectives of this study were to develop a robust protocol to measure the rate of hydrogen peroxide (H₂O₂) production in isolated perfused rat lungs, as an index of oxidative stress, and to determine the cellular sources of the measured H₂O₂ using the extracellular probe Amplex red (AR). AR was added to the recirculating perfusate in an isolated perfused rat lung. AR’s highly fluorescent oxidation product resorufin was measured in the perfusate. Experiments were carried out without and with rotenone (complex I inhibitor), thenoyltrifluoroacetone (complex II inhibitor), antimycin A (complex III inhibitor), potassium cyanide (complex IV inhibitor), or diohenylene iodonium (inhibitor of flavin-containing enzymes, e.g. NAD(P)H oxidase or NOX) added to the perfusate. We also evaluated the effect of acute changes in oxygen (O₂) concentration of ventilation gas on lung rate of H₂O₂ release into the perfusate. Baseline lung rate of H₂O₂ release was 8.45?±?0.31 (SEM) nmol/min/g dry wt. Inhibiting mitochondrial complex II reduced this rate by 76%, and inhibiting flavin-containing enzymes reduced it by another 23%. Inhibiting complex I had a small (13%) effect on the rate, whereas inhibiting complex III had no effect. Inhibiting complex IV increased this rate by 310%. Increasing %O₂ in the ventilation gas mixture from 15 to 95% had a small (27%) effect on this rate, and this O₂-dependent increase was mostly nonmitochondrial. Results suggest complex II as a potentially important source and/or regulator of mitochondrial H₂O₂, and that most of acute hyperoxia-enhanced lung rate of H₂O₂ release is from nonmitochondrial rather than mitochondrial sources.     

The movement of sulfate and thiosulfate into in vivo choroid plexus

The accumulation of sulfate (SO₄?) and thiosulfate (S₂O₃?) in the choroid plexus, brain, and cerebrospinal fluid (CSF) of the rat was measured at various plasma levels of these anions. Increasing the plasma SO₄ ? or S₂O₃ ? concentration levels 40- and 580-fold, respectively, resulted in a linear increase in CSF, brain and choroid plexus concentration of these ions. The relationship between the concentration of these ions in CSF and choroid plexus was also approximately linear over a wide CSF concentration range. In addition, S₂O₃? did not appear to influence the relation between the concentration of SO₄? in choroid plexus and CSF. The results seem to indicate that there is no saturation of the mechanism responsible for maintaining the low SO₄? or S₂O₃? concentration in CSF nor does there appear to be competition between these anions for clearance from the CSF. These findings are in conflict with data supporting the active transport of SO₄? and S₂O₃? from the CSF across the CSF-blood barrier (choroid plexus).     

Effects of inhalational anesthesia on blood gases and pH in California sea lions

Despite the widespread use of inhalational anesthesia with spontaneous ventilation in many studies of otariid pinnipeds, the effects and risks of anesthetic‐induced respiratory depression on blood gas and pH regulation are unknown in these animals. During such anesthesia in California sea lions (Zalophus californianus), blood gas and pH analyses of opportunistic blood samples revealed routine hypercarbia (highest P_CO2 = 128 mm Hg [17.1 kPa]), but adequate arterial oxygenation (P_O2 > 100 mm Hg [13.3 kPa] on 100% inspiratory oxygen). Respiratory acidosis (lowest pH = 7.05) was limited by the increased buffering capacity of sea lion blood. A markedly widened alveolar‐to‐arterial P_O2 difference was indicative of atelectasis and ventilation‐perfusion mismatch in the lung secondary to hypoventilation during anesthesia. Despite the generally safe track record of this anesthetic regimen in the past, these findings demonstrate the value of high inspiratory O₂ concentrations and the necessity of constant vigilance and caution. In order to avoid hypoxemia, we emphasize the importance of late extubation or at least maintenance of mask ventilation on O₂ until anesthetic‐induced respiratory depression is resolved. In this regard, whether for planned or emergency application, we also describe a simple, easily employed intubation technique with the Casper “zalophoscope” for sea lions.     

How do elevated CO2 and O3 affect the interception and utilization of radiation by a soybean canopy?

Net productivity of vegetation is determined by the product of the efficiencies with which it intercepts light (?_i) and converts that intercepted energy into biomass (?_c). Elevated carbon dioxide (CO₂) increases photosynthesis and leaf area index (LAI) of soybeans and thus may increase ?_i and ?_c; elevated O₃ may have the opposite effect. Knowing if elevated CO₂ and O₃ differentially affect physiological more than structural components of the ecosystem may reveal how these elements of global change will ultimately alter productivity. The effects of elevated CO₂ and O₃ on an intact soybean ecosystem were examined with Soybean Free Air Concentration Enrichment (SoyFACE) technology where large field plots (20‐m diameter) were exposed to elevated CO₂ (～550 μmol mol^?1) and elevated O₃ (1.2 × ambient) in a factorial design. Aboveground biomass, LAI and light interception were measured during the growing seasons of 2002, 2003 and 2004 to calculate ?_i and ?_c. A 15% increase in yield (averaged over 3 years) under elevated CO₂ was caused primarily by a 12% stimulation in ?_c , as ?_i increased by only 3%. Though accelerated canopy senescence under elevated O₃ caused a 3% decrease in ?_i, the primary effect of O₃ on biomass was through an 11% reduction in ?_c. When CO₂ and O₃ were elevated in combination, CO₂ partially reduced the negative effects of elevated O₃. Knowing that changes in productivity in elevated CO₂ and O₃ were influenced strongly by the efficiency of conversion of light energy into energy in plant biomass will aid in optimizing soybean yields in the future. Future modeling efforts that rely on ?_c for calculating regional and global plant productivity will need to accommodate the effects of global change on this important ecosystem attribute.     

Human Lung Homotransplantation

Left lung homotransplantation was performed in a 31-year-old man in terminal irreversible respiratory failure due to advanced silicosis. Within 10 minutes of completion of transplantation, arterial pO₂ rose from 52 to 211 mm. Hg, pCO₂ dropped from 90 to 43 mm. Hg, and pH rose from 7.15 to 7.42. On assisted ventilation, arterial O₂ tension was maintained within normal limits for the first four days. Thereafter, arterio-alveolar difference for O₂ increased to 300 mm. and that for CO₂ to 25 mm. Xenon-133 ventilation perfusion ratios confirmed differences between the two lungs. Terminally, bronchopneumonia and hypoxemia were present. Surfactant content of the lung was within normal limits. Postmortem examination revealed bronchopneumonia, bronchial infarction, lymphatic engorgement and mild rejection. Future efforts should emphasize selection of non-infected donors, minimal reliance on steroids for immunosuppression, cardiopulmonary bypass during transplantation, and more definite criteria for rejection.     

Heterogeneous Catalytic Oxidation of Phenanthrene by Hydrogen Peroxide in Soil Slurry: Kinetics,Mechanism, and Implication

The degradation of phenanthrene sorbed on soil has been carried out using a H₂O₂/goethite heterogeneous catalytic oxidation process. The effect of operating variables, such as the goethite concentration, pH, H₂O₂ concentration, soil organic matter, and bicarbonate ions has been investigated. The reaction followed pseudo-first order kinetics. The rate constants were evaluated and varied between 2.0×10^?4 and 1.1×10^?3?min^?1 depending on the H₂O₂ concentration. The highest rate of degradation of phenanthrene was observed at a H₂O₂ concentration of 5?M and 134.0?g/kg goethite. The intermediate product formed during the degradation of phenanthrene was identified to be salicylic acid that finally degraded to CO₂ and H₂O. H₂O₂ consumption continued as the OH radical attacked the salicylic acid. More than 80% consumption of the 5?M H₂O₂ took place within 30?min, and the degradation was almost complete after 3?h of reaction. Neutral pH was found to be effective in the removal of phenanthrene. Both soil organic matter (SOM) and bicarbonate ions in the soil inhibited the oxidation rate of phenanthrene.     

Detecting Deoxyhemoglobin in Spinal Cord Vasculature of the Experimental Autoimmune Encephalomyelitis Mouse Model of Multiple Sclerosis Using Susceptibility MRI and Hyperoxygenation

Susceptibility-weighted imaging (SWI) detects hypointensities due to iron deposition and deoxyhemoglobin. Previously it was shown that SWI detects hypointensities in the experimental autoimmune encephalomyelitis (EAE) model of multiple sclerosis (MS), most of which are due to intravascular deoxyhemoglobin, with a small proportion being due to iron deposition in the central nervous system parenchyma and demyelination. However, animals had to be sacrificed to differentiate these two types of lesions which is impractical for time course studies or for human application. Here, we proposed altering the inspired oxygen concentration during imaging to identify deoxyhemoglobin-based hypointensities in vivo. SWI was performed on lumbar spinal cords of naive control and EAE mice using 30% O₂ then 100% O2. Some mice were imaged using 30% O₂, 100% O₂ and after perfusion. Most SWI-visible hypointensities seen with 30% O₂ changed in appearance upon administration of 100% O₂, and were not visible after perfusion. That hypointensities changed with hyperoxygenation indicates that they were caused by deoxyhemoglobin. We show that increasing the inspired oxygen concentration identifies deoxyhemoglobin-based hypointensities in vivo. This could be applied in future studies to investigate the contribution of vascular-based hypointensities with SWI in EAE and MS over time.     

Dynamics of Nitric Oxide and Peroxynitrite During Global Brain Ischemia/Reperfusion in Rat Hippocampus: NO-sensor Measurement and Modeling Study

The dynamics of nitric oxide (NO) and peroxynitrite concentration changes during brain ischemia/reperfusion are poorly understood. In this paper, a NO-selective sensor was used to measure NO concentration changes in the rat brain hippocampus during global brain ischemia/reperfusion. Four-vessel occlusion model of transient global brain ischemia was used. Global cerebral ischemia was induced by occluding both common carotid arteries with artery nips (for 20 min) and reperfusion was induced by loosening the artery nips. Results showed that the changes of NO concentration during global brain ischemia/reperfusion could be divided into different stages. Together with the effects of O₂ tension changes and NO synthase (NOS) on nitric oxide levels, we determined five stages in the NO concentration profile: (1) acute O₂-limited decrease stage; (2) O₂-limited steady stage; (3) neuronal NOS activation stage; (4) acute O₂-recovery elevation stage; and (5) O₂-recovery steady stage. In addition, a chemical reaction network model was constructed to simulate the dynamics of peroxynitrite during the reperfusion stage, and the effects of a change in the NO formation rate on the dynamics of peroxynitrite were investigated specifically. Results show the rate of NO formation has a great influence on peroxynitrite dynamics.     

Analysis of relative contributions to the alveolar-arterial oxygen gradient

A fundamental analysis has been undertaken of O₂ transmission across a static inert gas with simultaneous diffusion of CO₂ in the reverse direction. The overall alveolar-arterial, (A-a) DO₂, gradient has then been derived as the simple sum of four terms representing shunt, ventilation/perfusion inequalities, membrane diffusion and airway diffusion with due allowance for any variation of each process throughout the lung. The expression provides a mathematical framework from which to isolate the net contribution of each process to the overall gradient—each value being a mean weighted according to the ventilation distribution of the gas exchange units. Airway diffusion resistance can be isolated with change of pressure and, from such data, has been estimated as about 6–7% of total (A-a) DO₂ in a healthy man breathing air at normal pressure. The same O₂ data has enabled the effective diameter of the functional gas exchange unit to be estimated as 14.2 mm.—well within the morphological limits for the secondary lobule.     

Noninvasive estimation of human tissue respiration with wavelet-analysis of oxygen saturation and blood flow oscillations in skin microvessels

Laser Doppler flowmetry, laser spectrophotometry of oxygen saturation, and the fluorescence determination of the NADH/FAD ratio were carried out in 30 subjects in the upper limb skin zones with and without arteriolovenular anastomoses (AVAs). It was demonstrated that the wavelet-analysis of oxygen saturation and blood flow oscillations in microvessels was an efficient approach to noninvasive estimation of the skin oxygen extraction (OE) and oxygen consumption (OC) rates. OE = (SaO₂ ? SvO₂)/SaO₂, where SaO₂ (%) and SvO₂ (%) are the oxygen saturations of arterial and venular blood, respectively. If the cardiac (A_c, perfusion units, p.u.) to respiratory rhythm amplitude (A_r, p.u.) ratio A_c/A_r ?? 1, SvO₂ = SO₂. If A_c/A_r > 1, SvO₂ = SO₂/(A_c/A_r). OC = M _nutr (SaO₂ ?? SvO₂) in p.u. · %O₂, where M _nutr is the nutritive blood flow value in p.u. M _nutr = M/SI, where SI is the shunting index of blood flow in microvessels. The perfusion, OE, and OC values were higher in the skin with AVAs than in the skin without AVAs. The perfusion and oxygen saturation values were more variable in the skin with AVAs. The oxygen diffusing from the tiniest arterioles and capillaries is the most important for tissue metabolism. The contribution of the total perfusion and the oxygen diffusion from arterioles to tissue metabolism increased under the tissue ischemia conditions.     

Hypoxic avoidance behaviour in cod (Gadus morhua L.): The effect of temperature and haemoglobin genotype

Hypoxia can influence fish growth, survival and on larger scales, population structure. These effects may be influenced by water temperature, and may vary intra-specifically with genotype. In Atlantic cod (Gadus morhua L.), the two haemoglobin homozygotes (Hb-I?11 and Hb-I?22) vary in oxygen affinity at different temperatures, which is thought to correspond to variation in hypoxia tolerance. We therefore tested if hypoxic avoidance behaviour in cod 1) depends on ambient temperature and 2) is modified by haemoglobin genotype. In a laminar flow choice box, we subjected juvenile cod to an initial phase of non-escapable hypoxia, and a subsequent recovery phase, where one habitat was kept at 20% O₂ saturation while the other was raised in steps to full saturation. The experiment was performed at 5 and 15 °C with Hb-I?11 and Hb-I?22 cod. Cod responded to inescapable hypoxia by reducing their overall swimming speed and then, at the initial levels of the recovery phase, avoiding the most hypoxic habitat, irrespective of temperature or genotype. Fish recovered quickly as O₂ levels increased, as evidenced by increased swimming speed and time spent in the most hypoxic habitat. The avoidance response depended strongly on temperature: the relative reduction in speed and avoidance of the most hypoxic habitat was more pronounced at 15 than at 5 °C. During the recovery phase, stressed fish initially maintained a higher swimming speed in the most hypoxic habitat. However, as O₂ increased, swimming speed in both habitats converged. This point of convergence occurred at a lower O₂ saturation at 5 °C. Fish ventilation rate in inescapable hypoxia was also higher at 15 °C. Haemoglobin genotype did not influence either ventilation rates or the nature of the hypoxic avoidance response at either temperature, but Hb-I?11 cod swam faster than Hb-I?22 cod in normoxia at 15 °C. Our results indicate that increased temperature limits the ability of cod of both haemoglobin genotypes to exploit hypoxic habitats. This may have negative future consequences for coastal cod stocks in light of increasing global temperatures and eutrophication in coastal waters.     

Temperature and respiratory function in ectothermic vertebrates

Pulmonary ventilation is adjusted to maintain balance between O₂ demands and CO₂ elimination, which is essential for acid–base status in land ectothermic vertebrates. Rising temperatures cause increases in O₂ consumption (Q₁₀ effect) and decreases in the O₂ affinity of hemoglobin (a rightward shift in the oxygen–hemoglobin dissociation curve). These changes in air-breathing ectotherms are not proportional, i.e., the increased ventilation is relatively smaller than the change in metabolic rate. Therefore, the ratio between ventilation and metabolic rate is reduced, and consequently blood pH changes inversely with temperature. The combination of high temperatures and hypoxia exposure results in an amplified increase of ventilation, which may be explained by the balance between increased O₂-demand and decreased O₂-supply as well as increased O₂-chemoreceptors sensitivity. High temperature also increases pulmonary diffusing capacity. Global warming is expected to have significant impacts on the world’s climate, with temperature changes affecting living organisms, in relation to their physiology and distribution. These physiological mechanisms and their capacity to respond appropriately to temperature illustrate the complexity of the relationship between ambient temperature and the respiratory function in ectothermic vertebrates, which are particularly susceptible to change in their environment.     

A Mathematical Model of the Controlled Plant of the Réspiratory System

Ability to predict the dynamic response of oxygen, carbon dioxide tensions, and pH in blood and tissues to abrupt changes in ventilation is important in the mathematical modeling of the respiratory system. In this study, the controlled plant (the amount and distribution of O₂ and CO₂) of the respiratory system is modeled. Although the body tissues are divided into a finite number of “compartments” (three tissue groups), in contrast to earlier models, the blood and tissue gas tensions within each compartment are considered to be continuously distributed in time and in one spatial coordinate. The mass conservation equations for oxygen and carbon dioxide involved in the blood-tissue gas exchange are described by a set of partial differential equations which take into account convection of O₂ and CO₂ caused by the flow of blood as well as diffusion due to local tension gradients. Nonlinear algebraic equations for the dissociation curves, which take into account the Haldane and Bohr effects in blood, are used to obtain the relationships between concentrations and partial pressures. Time-variable delays caused by the arterial and venous transport of the respiratory gases are also included. The model so constructed successfully reproduced actual O₂ and CO₂ tensions in arterial blood, and in muscle venous and mixed venous blood when ventilation was abruptly changed.     

Ventilatory response of the diamondback water snake,Natrix rhombifera to hypoxia, hypercapnia and increased oxygen demand

Summary Simultaneous measurements of ventilatory frequency, tidal volume, O₂ uptake, CO₂ output and cardiac frequency were made in the diamondback water snake,Natrix rhombifera while breathing hypoxic (15% to 5% O₂ in N₂) or hypercarbic (2% to 10% CO₂ and 21% O₂ in N₂) gases. The snakes responded to hypoxia by increasing tidal volume and decreasing ventilatory frequency resulting in little change in ventilation (50% increase at 5% inspired O₂), or O₂ uptake and only a light increase in CO₂ output. Hypercarbia to 4.2% inspired CO₂ resulted in a slight hyperventilation but ventilation was depressed at 6.3% inspired CO₂ and became erratic at higher concentrations. The resting rate of O₂ uptake was maintained throughout hypercapnia. Heart rate increased during hypoxia and decreased during hypercapnia. Cutaneous O₂ uptake increased during extreme hypoxia (5% inspired O₂) and cutaneous CO₂ output increased during hypercapnia, probably due to changes in the body-to-ambient gas gradients (Crawford and Schultetus, 1970). Both pulmonary oxygen uptake and ventilation were dramatically increased immediately following 10–15 min experimental dives. The increased ventilation was achieved primarily through an increased tidal volume.     

Mechanisms of stimulation of pulmonary prostacyclin synthesis at birth

In order to investigate the mechanism behind ventilation-induced pulmonary prostacyclin production at birth, chloralose anesthetized, exteriorized, fetal lambs were ventilated with a gas mixture that did not change blood gases (fetal gas) and unventilated fetal lungs were perfused with blood containing increased O₂ and decreased CO₂. Ventilation with fetal gas (3%O₂, 5%CO₂) increased net pulmonary prostacyclin (as 6-keto-PGF_1α production from −5.1 ± 4.4 to +12.6 ± 7.6 ng/kg·min. When ventilation was stopped, net pulmonary prostacyclin production returned to nondetectable levels. Ventilation with gas mixtures which increased pulmonary venous P_O2 and decreased P_O2 also stimulated pulmonary prostacyclin production, but did not have greater effects than did ventilation with fetal gas. In order to determine if increasing P_O2 or decreasing P_CO2 could stimulate pulmonary prostacyclin production independently from ventilation, unventilated fetal lamb lungs were perfused with blood that had P_O2 and P_CO2 similar to fetal blood, blood with elevated O₂, and blood that had P_O2 and P_CO2 values similar to arterial blood of newborn animals. Neither increased O₂ nor decreased CO₂ in the blood perfusing the lungs stimulated pulmonary prostacyclin synthesis. We conclude that the mechanism responsible for the stimulation of pulmonary prostacyclin with the onset of ventilation at birth is tissue stress during establishment of gaseous ventilation and rhythmic ventilation.     

Gill ventilation and O2 extraction during graded hypoxia in two ecologically distinct species of flatfish,the flounder (Platichthys flesus) and the plaice (Pleuronectes platessa)

Synopsis Gill ventilation, breathing frequency, breath volume, oxygen extraction from the ventilatory water current and oxygen uptake through the gills were measured in flounder, Platichthys flesus, and plaice, Pleuronectes platessa, at water O₂ tensions ranging from 35 to 155 mm Hg at 10° C. Ventilation volumes were similar in the two species at high water O₂ tension. Exposure to hypoxic water elicited a larger increase in ventilation in the flounder. The per cent extraction of O₂ from water decreased slightly in both species as water O₂ tension was lowered. At comparable levels of ventilation O₂ extraction was higher in flounder. At the higher levels of water O₂ tension, O₂ uptake across the gills of flounder was stable, the critical O₂ tension being between 60 and 100 mm Hg. The plaice behaved as an oxygen conformer over the entire range of O₂ tensions investigated. The superior ability of the flounder in maintaining OZ uptake across the gills during a reduction in water O₂ tension may in part explain why the species, unlike plaice, inhabits very shallow waters with large fluctuations in dissolved oxygen.     

PO2 of the metathoracic ganglion in response to progressive hypoxia in an insect

Mammals regulate their brain tissue P_O2 tightly, and only small changes in brain P_O2 are required to elicit compensatory ventilation. However, unlike the flow-through cardiovascular system of vertebrates, insect tissues exchange gases through blind-ended tracheoles, which may involve a more prominent role for diffusive gas exchange. We tested the effect of progressive hypoxia on ventilation and the P_O2 of the metathoracic ganglion (neural site of control of ventilation) using microelectrodes in the American locust, Schistocerca americana. In normal air (21 kPa), P_O2 of the metathoracic ganglion was 12 kPa. The P_O2 of the ganglion dropped as air P_O2 dropped, with ventilatory responses occurring when ganglion P_O2 reached 3 kPa. Unlike vertebrates, insects tolerate relatively high resting tissue P_O2 levels and allow tissue P_O2 to drop during hypoxia, activity and discontinuous gas exchange before activating convective or spiracular gas exchange. Tracheated animals, and possibly pancrustaceans in general, seem likely to generally experience wide spatial and temporal variation in tissue P_O2 compared with vertebrates, with important implications for physiological function and the evolution of oxygen-using proteins.     

Dependence of oxygen uptake on ambient PO 2 in isolated perfused frog skin

Summary Rates of O₂ uptake across isolated perfused skin of bullfrogs (Rana catesbeiana) were measured in relation to blood flow at three levels of ambient O₂ tension: normoxia (O₂ tension=152 torr), hypoxia (12% O₂, 87 torr) and hyperoxia (42% O₂, 306 torr). At bulk perfusion rates ranging from 3.4 to 10.1 l·cm^-2·min^-1, O₂ uptake was positively correlated with hemoglobin delivery rate in both normoxia and hyperoxia, but was independent of delivery rate in hypoxia. Mean O₂ uptake in normoxia was 3.8 nmol O₂·cm^-2·min^-1 at a delivery rate of 9.8 nmol·cm^-2·min^-1 and 6.5 nmol O₂·cm^-2·min^-1 at a delivery rate of 28.3 nmol·cm^-2·min^-1. At any given bulk perfusion rate, oxygen uptake averaged about 49% lower in hypoxia than in normoxia, decreasing in proportion to the reduction of O₂ tension difference between medium and blood. In hyperoxia, O₂ uptake did not increase proportionally with the difference in O₂ tension between blood and medium, averaging only 50% higher at a 2.4-fold greater O₂ tension difference. Cutaneous diffusing capacity for O₂ averaged 0.041 nmol O₂·cm^-2·torr^-1·min^-1 during the first hour of perfusion in normoxia, and was not affected by reduction of ambient O₂ tension. The results indicate that cutaneous O₂ uptake in hypoxia is highly diffusion limited, and consequently, increases in cutaneous perfusion can not effectively compensate for reduction of ambient O₂ tension. In hyperoxia, O₂ uptake may be substantially perfusion limited because of reduced blood O₂ capacitance at high O₂ saturations.Abbreviations O₂ capacitance - C _Hb hemoglobin concentration - D diffusing capacity - PO₂ medium-blood PO₂ difference - Hb flow, hemoglobin delivery rate - Hepes N-[2-Hydroxyethyl]piperacine-N-[2 ethanesulfonic acid] - L _diff extent of diffusion limitation - MO₂ oxygen uptake rate - PO₂ oxygen tension - S O₂ saturation