PO2 Profiles Research Articles

Distribution of Oxygen Tension on Microvessels and in Tissue of Rat Brain Cortex at Severe Arterial Hypocapnia

Arterial hypocapnia (AH), induced by voluntary or forced hyperventilation of the lungs, is accompanied by a decrease in cerebral blood flow (due to an increase in the arteriole tone) and an increase in the affinity of hemoglobin for oxygen. As a result, an insufficient oxygen supply to cortical tissue take place and zones with a critically low oxygen tension (pO2) are formed in brain tissue. The distribution of pO2 to cerebral cortex during AH has not been studied enough. The aim of the work was to evaluate the effectiveness of oxygen supply to brain tissue at the level of arterial and venous microvessels at AH. To do this, the following tasks were set: 1) to study the distribution of the pO2 on the arterial and venous microvessels of the rat cerebral cortex; 2) to analyze tissue pO2 profiles near the walls of these microvessels. On anesthetized Wistar rats under conditions of forced hyperventilation (PaCO2 = 17.1 ± 0.7 mm Hg), the distribution of oxygen tension on the wall of pial and radial arterioles with a lumen diameter of 7–70 μm and on the wall of pial and ascending venules with a lumen diameter of 7–300 µm was studied. In tissue, near the wall of cortical arterioles and venules with a lumen diameter of 10–20 μm, tissue pO2 profiles were measured. Measurements of pO2 during spontaneous breathing of the animal with air served as a control. All pO2 measurements were made using platinum polarographic microelectrodes with a tip diameter of 3–5 μm. Visualization of the electrode tip and microvessels was carried out using a LUMAM-K1 microscope with epiobjectives of the contact type. This work presents for the first-time direct measurements of pO2 on the walls of arterioles and venules of the rat cerebral cortex and in tissues at different distances from the walls of these microvessels at AH. It has been shown that AH results in significant decrease in the oxygen supply to cerebral cortex, that is manifested by a significant drop of the pO2’s on venous microvessels and in tissue in the immediate vicinity of the studied microvessels. It has been shown, that the role of arterioles as a direct source of oxygen to brain tissue, is significantly reduced during arterial hypocapnia. Forced hyperventilation results in significant deterioration of oxygen supply to cerebral cortex, despite elevated pO2 values in the systemic arterial blood and in blood of systemic cerebral veins (sagittal sinus).

Tissue oxygen partial pressure as a viability metric for ex vivo brain tissue slices

BackgroundDespite the prevalent use of the ex vivo brain slice preparation in neurophysiology research, a reliable method for judging tissue viability ― and thus suitability of a slice for inclusion in an experiment ― is lacking. The utility of indirect electrophysiological measures of tissue health is model-specific and needs to be used cautiously. In this study, we verify a more direct test of slice viability, based on tissue oxygen consumption rate. New methodWe hypothesised that the minimum intra-slice partial pressure of oxygen (pO2min) would correlate with tissue oxygen consumption rate, providing an accessible method for reliably assessing tissue viability status. Using mouse brain cortex slices, we measured tissue oxygen consumption rate using a Fick’s law diffusion–consumption model applied to full intra-tissue pO2 profiles and compared this to pO2min and 2,3,5-triphenol tetrazolium chloride (TTC) viability staining. ResultsTissue pO2min correlated strongly with oxygen consumption rate in both neurophysiological active and quiescent tissue (in “no-magnesium” and “normal” artificial cerebrospinal fluid, respectively) (R2 =49.7% and 42.1%, respectively). Both correlated with TTC viability stain. Oxygen consumption rate was positively related to the frequency of seizure-like event activity in no-magnesium artificial cerebrospinal fluid (R2 = 44.8%). Comparison with existing methodsWhile measurement of tissue oxygen levels and oxygen consumption is not new, intra-tissue pO2min is a novel approach to assess brain slice viability. ConclusionThe results confirm that tissue oxygen minimum pO2min is a robust metric for estimating tissue viability status — the lower the pO2min, the healthier the tissue.

Determination of Krogh Coefficient for Oxygen Consumption Measurement from Thin Slices of Rodent Cortical Tissue Using a Fick's Law Model of Diffusion.

To investigate the impact of experimental interventions on living biological tissue, ex vivo rodent brain slices are often used as a more controllable alternative to a live animal model. However, for meaningful results, the biological sample must be known to be healthy and viable. One of the gold-standard approaches to identifying tissue viability status is to measure the rate of tissue oxygen consumption under specific controlled conditions. Here, we work with thin (400 μm) slices of mouse cortical brain tissue which are sustained by a steady flow of oxygenated artificial cerebralspinal fluid (aCSF) at room temperature. To quantify tissue oxygen consumption (Q), we measure oxygen partial pressure (pO2) as a function of probe depth. The curvature of the obtained parabolic (or parabola-like) pO2 profiles can be used to extract Q, providing one knows the Krogh coefficient Kt, for the tissue. The oxygen trends are well described by a Fick's law diffusion-consumption model developed by Ivanova and Simeonov, and expressed in terms of ratio (Q/K), being the rate of oxygen consumption in tissue divided by the Krogh coefficient (oxygen diffusivity × oxygen solubility) for tissue. If the fluid immediately adjacent to the tissue can be assumed to be stationary (i.e., nonflowing), one may invoke conservation of oxygen flux K·(∂P/∂x) across the interface to deduce (Kt/Kf), the ratio of Krogh coefficients for tissue and fluid. Using published interpolation formulas for the effect of salt content and temperature on oxygen diffusivity and solubility for pure water, we estimate Kf, the Krogh coefficient for aCSF, and hence deduce the Kt coefficient for tissue. We distinguish experimental uncertainty from natural biological variability by using pairs of repeated profiles at the same tissue location. We report a dimensionless Krogh ratio (Kt/Kf)=0.562±0.088 (mean ± SD), corresponding to a Krogh coefficient Kt=(1.29±0.21)×10-14 mol/(m·s·Pa) for mouse cortical tissue at room temperature, but acknowledge the experimental limitation of being unable to verify that the fluid boundary layer is truly stationary. We compare our results with those reported in the literature, and comment on the challenges and ambiguities caused by the extensive use of 'biologically convenient' non-SI units for tissue Krogh coefficient.

Modeling the impact of tissue oxygen profiles and oxygen depletion parameter uncertainties on biological response and therapeutic benefit of FLASH.

Ultra-high dose rate (FLASH) radiation has been reported to efficiently suppress tumor growth while sparing normal tissue; however, the mechanism of the differential tissue sparing effect is still not known. Oxygen has long been known to profoundly impact radiobiological responses, and radiolytic oxygen depletion has been considered to be a possible cause or contributor to the FLASH phenomenon. This work investigates the impact of tissue pO2 profiles, oxygen depletion per unit dose (g), and the oxygen concentration yielding half-maximum radiosensitization (the average of its maximum value and one) (k) in tumor and normal tissue. We developed a model that considers the dependent relationship between oxygen depletion and change of radiosensitivity by FLASH irradiation. The model assumed that FLASH irradiation depletes intracellular oxygen more rapidly than it diffuses into the cell from the extracellular environment. Cell survival was calculated based on the linear quadratic-linear model and the radiosensitivity related parameters were adjusted in 1Gy increments of the administered dose. The model reproduced published experimental data that were obtained with different cell lines and oxygen concentrations, and was used to analyze the impact of parameter uncertainties on the radiobiological responses. This study expands the oxygen depletion analysis of FLASH to normal human tissue and tumor based on clinically determined aggregate and individual patient pO2 profiles. The results show that the pO2 profile is the most essential factor that affects biological response and analyses based on the median pO2 rather than the full pO2 profile can be unreliable and misleading. Additionally, the presence of a small fraction of cells on the threshold of radiobiologic hypoxia substantially alters biological response due to FLASH oxygen depletion. We found that an increment in the k value is generally more protective of tumor than normal tissue due to a higher frequency of lower pO2 values in tumors. Variation in the g value affects the dose at which oxygen depletion impacts response, but does not alter the dose-dependent response trends, if the g value is identical in both tumor and normal tissue. The therapeutic efficacy of FLASH oxygen depletion is likely patient and tissue-dependent. For breast cancer, FLASH is beneficial in a minority of cases; however, in a subset of well oxygenated tumors, a therapeutic gain may be realized due to induced normal tissue hypoxia.

The fallacy of the Pcrit - are there more useful alternatives?

Pcrit - generally defined as the PO2 below which the animal can no longer maintain a stable rate of O2 consumption (ṀO2 ), such that ṀO2 becomes dependent upon PO2 - provides a single number into which a vast amount of experimental effort has been invested. Here, with specific reference to water-breathers, I argue that this focus on the Pcrit is not useful for six reasons: (1) calculation of Pcrit usually involves selective data editing; (2) the value of Pcrit depends greatly on the way it is determined; (3) there is no good theoretical justification for the concept; (4) Pcrit is not the transition point from aerobic to anaerobic metabolism, and it disguises what is really going on; (5) Pcrit is not a reliable index of hypoxia tolerance; and (6) Pcrit carries minimal information content. Preferable alternatives are loss of equilibrium (LOE) tests for hypoxia tolerance, and experimental description of full ṀO2 versus PO2 profiles accompanied by measurements of ventilation, lactate appearance and metabolic rate by calorimetry. If the goal is to assess the ability of the animal to regulate ṀO2 from this profile in a mathematical fashion, promising, more informative alternatives to Pcrit are the regulation index and Michaelis-Menten or sigmoidal allosteric analyses.

Long-term viability and function of transplanted islets macroencapsulated at high density are achieved by enhanced oxygen supply

Transplantation of encapsulated islets can cure diabetes without immunosuppression, but oxygen supply limitations can cause failure. We investigated a retrievable macroencapsulation device wherein islets are encapsulated in a planar alginate slab and supplied with exogenous oxygen from a replenishable gas chamber. Translation to clinically-useful devices entails reduction of device size by increasing islet surface density, which requires increased gas chamber pO2. Here we show that islet surface density can be substantially increased safely by increasing gas chamber pO2 to a supraphysiological level that maintains all islets viable and functional. These levels were determined from measurements of pO2 profiles in islet-alginate slabs. Encapsulated islets implanted with surface density as high as 4,800 islet equivalents/cm3 in diabetic rats maintained normoglycemia for more than 7 months and provided near-normal intravenous glucose tolerance tests. Nearly 90% of the original viable tissue was recovered after device explantation. Damaged islets failed after progressively shorter times. The required values of gas chamber pO2 were predictable from a mathematical model of oxygen consumption and diffusion in the device. These results demonstrate feasibility of developing retrievable macroencapsulated devices small enough for clinical use and provide a firm basis for design of devices for testing in large animals and humans.

Microbes vs. chemistry in the origin of the anaerobic gut lumen

The succession from aerobic and facultative anaerobic bacteria to obligate anaerobes in the infant gut along with the differences between the compositions of the mucosally adherent vs. luminal microbiota suggests that the gut microbes consume oxygen, which diffuses into the lumen from the intestinal tissue, maintaining the lumen in a deeply anaerobic state. Remarkably, measurements of luminal oxygen levels show nearly identical pO2 (partial pressure of oxygen) profiles in conventional and germ-free mice, pointing to the existence of oxygen consumption mechanisms other than microbial respiration. In vitro experiments confirmed that the luminal contents of germ-free mice are able to chemically consume oxygen (e.g., via lipid oxidation reactions), although at rates significantly lower than those observed in the case of conventionally housed mice. For conventional mice, we also show that the taxonomic composition of the gut microbiota adherent to the gut mucosa and in the lumen throughout the length of the gut correlates with oxygen levels. At the same time, an increase in the biomass of the gut microbiota provides an explanation for the reduction of luminal oxygen in the distal vs. proximal gut. These results demonstrate how oxygen from the mammalian host is used by the gut microbiota, while both the microbes and the oxidative chemical reactions regulate luminal oxygen levels, shaping the composition of the microbial community throughout different regions of the gut.

Continuous arterial PO2profiles in unrestrained, undisturbed aquatic turtles during routine behaviors.

Mammals and birds maintain high arterial partial pressure of oxygen (PO2 ) values in order to preserve near-complete hemoglobin (Hb) oxygen (O2) saturation. In diving mammals and birds, arterial O2 follows a primarily monotonic decline and then recovers quickly after dives. In laboratory studies of submerged freshwater turtles, arterial O2 depletion typically follows a similar pattern. However, in these studies, turtles were disturbed, frequently tethered to external equipment and confined either to small tanks or breathing holes. Aquatic turtles can alter cardiac shunting patterns, which will affect arterial PO2 values. Consequently, little is known about arterial O2 regulation and use in undisturbed turtles. We conducted the first study to continuously measure arterial PO2 using implanted microelectrodes and a backpack logger in undisturbed red-eared sliders during routine activities. Arterial PO2 profiles during submergences varied dramatically, with no consistent patterns. Arterial PO2 was also lower than previously reported during all activities, with values rarely above 50 mmHg (85% Hb saturation). There was no difference in mean PO2 between five different activities: submerged resting, swimming, basking, resting at the surface and when a person was present. These results suggest significant cardiac shunting occurs during routine activities as well as submergences. However, the lack of relationship between PO2 and any activity suggests that cardiac shunts are not regulated to maintain high arterial PO2 values. These data support the idea that cardiac shunting is the passive by-product of regulation of vascular resistances by the autonomic nervous system.

The effects of D-allose on transient ischemic neuronal death and analysis of its mechanism.

The present study investigates the neuroprotective effects of d-allose, a rare sugar, against ischemia/reperfusion injury in a gerbil model. Transient forebrain ischemia was induced by occlusion of the bilateral common carotid arteries for 5 min. D-Allose was intravenously injected before and after ischemia (200 mg/kg). Extracellular glutamate and lactate release from the gerbil brain, and PO₂ profiles were monitored during ischemia and reperfusion. We also examined neuronal death and oxidative damage in the hippocampus one week after ischemia reperfusion, and investigated functional outcome. D-Allose administration suppressed glutamate and lactate release compared to vehicle controls. Brain damage, 8-OHdG levels (a marker of oxidative stress) and locomotor activities were significantly decreased by D-allose treatment. The present results suggest that d-allose reduces delayed neuronal death and behavioral deficits after transient ischemia by changing cerebral metabolism and inhibiting oxidative stress.

Retinal Oxygen distribution in normal and pathological cases; animal models and humans

AbstractThe distribution of PO2 close to the vitreoretinal interface is heterogeneous, found higher near the arteriolar wall. Preretinal and transretinal PO2 profiles indicate that O2 diffusion from the arterioles affects the PO2 in the juxta‐arteriolar preretinal region. Both the preretinal and inner retinal PO2 recorded far from the vessels remain constant in all retinal areas. The oxygen tension (PO2) in the inner half of the retina remains largely unaffected by moderate changes in perfusion pressure. In addition a constant PO2 is observed during systemic PaO2 changes induced either by hyperoxia or hypoxia. However, an increase of PaCO2 (hypercapnia), as well as an intravenous injection of acetazolamide (carbonic anhydrase inhibitor) can both lead to an increase of preretinal PO2 due to retinal vessels dilatation. In the case of eyes with experimental branch retinal vein occlusion, PO2 values, within the inner retinal layers, are indicative of hypoxic conditions, whereas in adjacent unaffected retinal areas the PO2 remain normal. In diabetic patients undergoing vitrectomy, reports have shown a lowered vitreal POg in the affected retinal areas. Occlusion of the retinal circulation renders most of the inner retina anoxic.

Oxygen distribution in the retina

AbstractPurpose To evaluate the distibution of the preretinal and transretinal partial pressure of oxygen(PO2) in normal and ischemic retinas.Methods Evaluation of either the preretinal or intraretinal oxygen partial pressure (PO2) distribution, using oxygen sensitive microelectrodes, in normal or ischemic retinal conditions.Results The distribution of PO2 close to the vitreoretinal interface is heterogeneous, being higher near the arteriolar wall. Preretinal and transretinal PO2 profiles indicate that O2 diffusion from the arterioles affects the PO2 in the juxta‐arteriolar preretinal region. Both the preretinal and inner retinal PO2 recorded far from the vessels remain constant in all retinal areas. The oxygen tension (PO2) in the inner half of the retina remains largely unaffected by moderate changes in perfusion pressure, systemic PaO2 changes occuring during either hyperoxia or hypoxia. However, an increase in PaCO2 (hypercapnia), as well as an intravenous injection of acetazolamide (carbonic anhydrase inhibitor) both lead to an increase in preretinal PO2 due to dilation of the retinal vessels. In eyes with experimental branch retinal vein occlusion, PO2 values within the inner retinal layers are indicative of hypoxic conditions, whereas adjacent areas appear to remain normal. In diabetic patients undergoing vitrectomy a lowered vitreal PO2 in the affected retinal areas has also reported.Occlusion of the retinal circulation renders most of the inner retina anoxic.Conclusion Thanks to the autoregulatory ability of the retinal circulation, the oxygen tension (PO2) in the inner half of the retina, remains largely unaffected during physiological stimuli. In both normal and inner retinal ischemic conditions,the oxygen supply from the choroid is sufficient to support only the photoreceptor inner segments.

Oxygen consumption and distribution in the Long-Evans rat retina

The purpose of this study was to investigate the oxygen distribution and consumption in the pigmented Long-Evans rat retina in vivo during dark and light adaptation, and to compare these results to previous work on cat and albino rat. Double-barreled microelectrodes recorded both intraretinal PO2 depth profiles and the electroretinogram (ERG), which was used to identify the boundaries of the retina. Light adaptation decreased photoreceptor oxygen consumption per unit volume (Qav) from 3.0 ± 0.4 ml·100 g−1 min−1 (mean ± SEM) in darkness to 1.8 ± 0.2 ml·100 g−1 min−1 and increased minimum outer retinal PO2 at the inner segments (Pmin) from 17.4 ± 3.0 to 29.9 ± 5.3 mmHg. The effects of light on outer retinal PO2 and Qav were similar to those previously observed in cat, monkey, and albino rats; however, dark-adapted Pmin was higher in rat than cat. The parameters derived from fitting the oxygen diffusion model to the rat data were compared to those from cat. Oxygen consumption of the inner segments (Q2) and choroidal PO2 (PC) in rat and cat were similar. Pmin was higher in rat than in cat for two reasons: first, rat photoreceptors have a shorter oxygen consuming region; and second, the retinal circulation supplied a greater fraction of consumed oxygen to rat photoreceptors. The average PO2 across the inner retina (PIR) was not different in dark adaptation (25.4 ± 4.8 mmHg) and light adaptation (28.8 ± 5.4 mmHg) when measured from PO2 profiles. However, with the microelectrode stationary at 9–18% retinal depth, a small consistent decrease in PO2 occurred during illumination. Flickering light at 6 Hz decreased inner retinal PO2 significantly more than an equivalent steady illumination, suggesting that changes in blood flow did not completely compensate for increased metabolism. This study comprehensively characterized rat retinal oxygenation in both light and dark, and determined the similarities and differences between rat and cat retinas.

Regulation of retinal tissue oxygenation

Abstract Purpose To evaluate the changes in the retinal oxygen partial pressure (PO2) following physiological stimuli. Methods Evaluation of either the preretinal and intraretina partial pressure of oxygen (PO2) distribution, using oxygen sensitive microelectrodes, in various animal models. Measurements were obtained during changes of the perfusion pressure, systemic hyperoxia, hypoxia, hypercapnia, carbogen breathing and following carbonic anydrase inhibitors use. Results The oxygen tension (PO2) in the inner half of the retina remains largely unaffected by moderate changes in perfusion pressure. The increase of the systemic PaO2 through breathing of 100% O2 (hyperoxia) induces endothelin (ET) mediated marked vasoconstriction of the inner retinal arterioles in both anesthetized animals and normal human subjects. The regulatory vasoconstriction maintains the PO2 in retinal tissue constant. A decrease in PaO2 (hypoxia) induces a vasodilation of the retinal arterioles through endothelium‐derived NO release. As a result, trans‐retinal PO2 profiles made during steps of systemic hypoxia have shown that the values measured in the inner retina up to half of its thickness, remain rather stable. By contrast, the PO2 values, measured close to the choroid and in the outer retina, decrease in a linear manner with the decrease of the PaO2. An increase in the PaCO2 (hypercapnia) of arteriolar blood, produces an increase in retinal blood flow and retinal tissue PO2. Intravenous injection of acetazolamide (carbonic anhydrase inhibitor) produces an increase in preretinal PO2 due to dilation of the retinal vessels Conclusion Thanks to the autoregulatory capability of the retinal circulation, the oxygen tension (PO2) in the inner half of the retina, remains largely unaffected during physiological stimuli.

Tissue Oxygen Tension Profiles Close to Brain Arterioles and Venules in the Rat Cerebral Cortex during the Development of Acute Anemia

Acute anemia (stages 1 and 2) led to decreases in pO2 at the walls of radial venules (lumen diameter 13.1 +/- 0.5 microm) and in the tissues at distances of up to 40 mum from the walls, indicating increased extraction of oxygen from the blood by the smallest microvessels. Further decreases in the blood hemoglobin concentration (stage 3) did not produce any significant changes in the nature of tissue pO2 profiles close to the walls of these microvessels. In the intercapillary space, tissue pO2 decreased in proportion to the decrease in the systemic blood hemoglobin concentration, though tissue hypoxia (p(t)O2 < or = 8-10 mmHg) was seen only in tissue in which the microvessels had inadequate (decreased) blood flow responses.

Retinal photocoagulation and oxygenation

Abstract Purpose The clinical role of photocoagulation for the treatment of hypoxia related complications of retinal ischemic microangiopathies is well established. Methods Measurements of the partial pressure of oxygen (PO2) distribution within the the retina in various animal species using oxygen sensitive microelectrodes and evaluation of the retinal vessels reactivity by laser doppler velocimetry gave additional insights concerning photocoagulation mechanisms. Results The PO2 within the vitreo‐retinal interface is heterogeneous. Preretinal and trans‐retinal PO2 profiles indicate that the preretinal PO2 far away from vessels remain constant in all retinal areas. Intervascular intraretinal PO2 gradually decreases from both the vitreo‐retinal interface and the choroid towards the mid‐retina. Close to the pigment epithelium, it is significantly higher than at the vitreoretinal interface due to the much higher O2 supply provided by choroidal compaires to retinal circulation. Laser photocoagulation reduces the outer retina O2 consumption and allows O2 diffusion into the inner retina from the choroid raising the PO2 in the inner healthy retinal layers and in the preretinal intervascular normal areas. In this way laser treatment relieves retinal hypoxia in experimental branch vein occlusion (BRVO). In patients with diabetic retinopathy (DR), the retinal PO2 is higher in areas previously treated with laser. Following photocoagulation, the resulting reversal of hypoxia, the retinal vasculature constriction and the improvement of the regulatory response to hyperoxia all affect favorably both the retinal neovascularisation and macular edema. Conclusion Photocoagulation induces an increase of the inner retinal oxygenation reversing the retinal hypoxia and improving the regulatory response of the retinal vessels

A mathematical model of O2 transport in the rat outer medulla. II. Impact of outer medullary architecture

we extended the region-based mathematical model of the urine-concentrating mechanism in the rat outer medulla (OM) developed by Layton and Layton (Am J Physiol Renal Physiol 289: F1346-F1366, 2005) to examine the impact of the complex structural organization of the OM on O(2) transport and distribution. In the present study, we investigated the sensitivity of predicted Po(2) profiles to several parameters that characterize the degree of OM regionalization, boundary conditions, structural dimensions, transmural transport properties, and relative positions and distributions of tubules and vessels. Our results suggest that the fraction of O(2) supplied to descending vasa recta (DVR) that reaches the inner medulla, i.e., a measure of the axial Po(2) gradient in the OM, is insensitive to parameter variations as a result of the sequestration of long DVR in the vascular bundles. In contrast, O(2) distribution among the regions surrounding the vascular core strongly depends on the radial positions of medullary thick ascending limbs (mTALs) relative to the vascular core, the degree of regionalization, and the distribution of short DVR along the corticomedullary axis. Moreover, if it is assumed that the mTAL active Na(+) transport rate decreases when mTAL Po(2) falls below a critical level, O(2) availability to mTALs has a significant impact on the concentrating capability of the model OM. The model also predicts that when the OM undergoes hypertrophy, its concentrating capability increases significantly only when anaerobic metabolism supports a substantial fraction of the mTAL active Na(+) transport and is otherwise critically reduced by low interstitial and mTAL luminal Po(2) in a hypertrophied OM.

O2 store management in diving emperor penguins

In order to further define O(2) store utilization during dives and understand the physiological basis of the aerobic dive limit (ADL, dive duration associated with the onset of post-dive blood lactate accumulation), emperor penguins (Aptenodytes forsteri) were equipped with either a blood partial pressure of oxygen (P(O(2))) recorder or a blood sampler while they were diving at an isolated dive hole in the sea ice of McMurdo Sound, Antarctica. Arterial P(O(2)) profiles (57 dives) revealed that (a) pre-dive P(O(2)) was greater than that at rest, (b) P(O(2)) transiently increased during descent and (c) post-dive P(O(2)) reached that at rest in 1.92+/-1.89 min (N=53). Venous P(O(2)) profiles (130 dives) revealed that (a) pre-dive venous P(O(2)) was greater than that at rest prior to 61% of dives, (b) in 90% of dives venous P(O(2)) transiently increased with a mean maximum P(O(2)) of 53+/-18 mmHg and a mean increase in P(O(2)) of 11+/-12 mmHg, (c) in 78% of dives, this peak venous P(O(2)) occurred within the first 3 min, and (d) post-dive venous P(O(2)) reached that at rest within 2.23+/-2.64 min (N=84). Arterial and venous P(O(2)) values in blood samples collected 1-3 min into dives were greater than or near to the respective values at rest. Blood lactate concentration was less than 2 mmol l(-1) as far as 10.5 min into dives, well beyond the known ADL of 5.6 min. Mean arterial and venous P(N(2)) of samples collected at 20-37 m depth were 2.5 times those at the surface, both being 2.1+/-0.7 atmospheres absolute (ATA; N=3 each), and were not significantly different. These findings are consistent with the maintenance of gas exchange during dives (elevated arterial and venous P(O(2)) and P(N(2)) during dives), muscle ischemia during dives (elevated venous P(O(2)), lack of lactate washout into blood during dives), and arterio-venous shunting of blood both during the surface period (venous P(O(2)) greater than that at rest) and during dives (arterialized venous P(O(2)) values during descent, equivalent arterial and venous P(N(2)) values during dives). These three physiological processes contribute to the transfer of the large respiratory O(2) store to the blood during the dive, isolation of muscle metabolism from the circulation during the dive, a decreased rate of blood O(2) depletion during dives, and optimized loading of O(2) stores both before and after dives. The lack of blood O(2) depletion and blood lactate elevation during dives beyond the ADL suggests that active locomotory muscle is the site of tissue lactate accumulation that results in post-dive blood lactate elevation in dives beyond the ADL.

Returning on empty: extreme blood O2 depletion underlies dive capacity of emperor penguins

Blood gas analyses from emperor penguins (Aptenodytes forsteri) at rest, and intravascular P(O(2)) profiles from free-diving birds were obtained in order to examine hypoxemic tolerance and utilization of the blood O(2) store during dives. Analysis of blood samples from penguins at rest revealed arterial P(O(2))s and O(2) contents of 68+/-7 mmHg (1 mmHg= 133.3 Pa) and 22.5+/-1.3 ml O(2) dl(-1) (N=3) and venous values of 41+/-10 mmHg and 17.4+/-2.9 ml O(2) dl(-1) (N=9). Corresponding arterial and venous Hb saturations for a hemoglobin (Hb) concentration of 18 g dl(-1) were >91% and 70%, respectively. Analysis of P(O(2)) profiles obtained from birds equipped with intravascular P(O(2)) electrodes and backpack recorders during dives revealed that (1) the decline of the final blood P(O(2)) of a dive in relation to dive duration was variable, (2) final venous P(O(2)) values spanned a 40-mmHg range at the previously measured aerobic dive limit (ADL; dive duration associated with onset of post-dive blood lactate accumulation), (3) final arterial, venous and previously measured air sac P(O(2)) values were indistinguishable in longer dives, and (4) final venous P(O(2)) values of longer dives were as low as 1-6 mmHg during dives. Although blood O(2) is not depleted at the ADL, nearly complete depletion of the blood O(2) store occurs in longer dives. This extreme hypoxemic tolerance, which would be catastrophic in many birds and mammals, necessitates biochemical and molecular adaptations, including a shift in the O(2)-Hb dissociation curve of the emperor penguin in comparison to those of most birds. A relatively higher-affinity Hb is consistent with blood P(O(2)) values and O(2) contents of penguins at rest.

Quantifying the role of oxygen pressure in tissue function

it has been suggested that oxygen had reached significant levels in the earth's oceans as early as 2.5 billion years ago and has rapidly increased to near current levels about 50 million years later ([6][1]). The appearance of oxygen dramatically changed the chemical composition of the oceans and

Influence of radiographic contrast media on myocardial oxygen tension: a randomized, NaCL-controlled comparative study of iodixanol versus iomeprol in pigs

To examine how a one-time bolus injection of radiographic contrast media (RCM; iodixanol 320 and iomeprol 350) into the left coronary artery of six pigs affects tissue oxygen tension in the artery's supply area (pO(2 )LAD) compared to a 0.9% sodium-chloride (NaCl) bolus. Each animal received a total of three boluses: one iodixanol, one iomeprol, and one NaCl (10 ml each). The radiographic contrast media and NaCl boluses were randomly assigned, and pO(2) profiles were recorded. 26.7+/-16.4 s after iodixanol injection, pO(2) LAD had declined by 3.5% from 42.2+/-5.6 mmHg to 40.7+/-5.9 mmHg (P = 0.0357). After 53+/-16.7 s, the initial value was restored. The pO(2) LAD was 41.9+/-7.4 mmHg before iomeprol injection, and, 303.3+/-58.9 s after injection, pO(2) LAD had declined by 13.1% to 36.4+/-7.5 mmHg (P = 0.0001). After 577+/-22 s, the initial value was restored. The bolus application of an isotonic NaCl solution resulted in no effect on pO(2) LAD. Immediately after injection, it increased by 3%. In the supply area of the right coronary artery and the peripheral skeletal muscle, no effect of the RCM or NaCl on tissue oxygen tension was observed. Furthermore, no effect on tissue temperature, heart rate, systolic and diastolic blood pressure, or cardiac output per minute occurred. The injection of RCM in a coronary artery can result in a significant local contrast-medium-induced microcirculation disorder. The high viscosity of iodixanol led to a very short-term insignificant effect on the microcirculation, while iomeprol induced a slight time-delayed pO(2) decrease, which might be caused by the rigidification of erythrocytes. In comparison to a previous study with iopromide, the influence of iodixanol and iomeprol on myocardial oxygen tension was markedly less pronounced.