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P Scheid

Publications and source records attributed to P Scheid.

At least 73 records · Page 4Linked to original sources

Diffusion limitation of O2 supply to tissue in homogeneous and heterogeneous models.

The role of diffusion limitation in O2 supply was studied in cross-sectional elements of the Krogh cylinder model (with O2 supply from a central capillary) and of the solid cylinder model (with O2 supply from the outer surface). The effect of diffusion limitation was quantified in terms of the ratio O2 uptake/O2 requirement (= fraction of cross-sectional area supplied with O2), assuming local O2 requirement per unit volume to be constant and independent of PO2 at PO2 greater than 0. Calculations were performed for single cylinders of varied radius and O2 requirement (homogeneous models). Unequal distribution of diffusion conditions was represented by a model composed of three sorts of Krogh or solid cylinders, with radii in relation 3: square root of 3:1, but of equal cross-sectional area, i.e. number of cylinders of each sort in relation 1:3:9 (heterogeneous models). The results revealed the following main features. (1) At the same outer radius, diffusion limitation sets in at a smaller O2 requirement, and increases more steeply with increasing O2 requirement, in the homogeneous Krogh cylinder model compared with the homogeneous solid cylinder model. A similar behavior is observed when the radius of the cylinder section is increased at constant O2 requirement. (2) Diffusion limitation in the heterogeneous model sets in at a lower O2 requirement value, and increases more gradually with increasing O2 requirement, than in the corresponding homogeneous models with the same average cylinder diameter. This behavior is due to sequential onset, in the heterogeneous model, of anoxia in the cylinder sections of different radii. We conclude that diffusion heterogeneity has to be taken into account when the role of diffusion limitation in tissue O2 supply is investigated.

Animals↗

Effect of the curvature of the O2 equilibrium curve on alveolar O2 uptake: theory.

The effect of the curvature of the O2 equilibrium curve (OEC), in the range between mixed venous and alveolar PO2, on alveolar O2 uptake was quantitatively investigated in a simple homogeneous lung model. The O2 uptake achieved with a linear OEC (Mlin) was subtracted from the O2 uptake (M) attained with the physiologically curved, sigmoid OEC, and the relative difference was considered as the 'curvature effect', CE [= (M - Mlin)/M], indicating, if positive, the enhancement of O2 uptake by the non-linearity of the OEC. Calculations show CE to be close to nil (less than 1%) in normal lungs during rest both in normoxia and in hypoxia. CE is more important in heavy exercise both in normoxia (CE less than 19%) or slight hypoxia (CE less than 15%). In deep hypoxia, CE is negligible again even during exercise. Thus, the simplified approach to the analysis of alveolar O2 uptake using a linear OEC, in the mixed venous-to-alveolar PO2 range, constitutes in most cases a valid approximation.

Models, Biological↗

Diffusion and perfusion limitation in alveolar O2 exchange: shape of the blood O2 equilibrium curve.

The limitations imposed by diffusion (Ldiff) and perfusion (Lperf) on alveolar gas exchange can be estimated using a simple model of alveolar-capillary gas transfer (Piiper and Scheid (1981) Respir, Physiol. 46: 193-208). These limitations indicate the fractional increase of gas exchange that would occur by raising pulmonary conductances for diffusion or perfusion to functionally infinite values. The (simple) model assumes linear relations between concentration and partial pressure for the gases studied. We have investigated in this study the effects of this assumption for estimating Ldiff and Lperf for O2 whose blood equilibrium curve is particularly non-linear in normoxia. The calculations suggest that Lperf is only slightly overestimated by the assumption of linear blood O2 binding. For Ldiff, there is a significant overestimation in normoxia, but in hypoxia the linear equilibrium curve yields sufficiently accurate estimates. Calculations for data estimated for man on the summit of Mt. Everest suggest that alveolar O2 uptake in deep hypoxia at rest is mainly limited by perfusion and to a lesser degree by diffusion (Lperf greater than Ldiff). For the sustained exercise of climbing, on the other hand, diffusion limitation is more prominent than perfusion limitation (Ldiff greater than Lperf). Large values of Ldiff are estimated for normoxic O2 uptake across the skin of the gill-less and lung-less salamander, and here, the effects of the alinearity of the O2 equilibrium curve are pronounced. It is concluded that the simplified model of alveolar-capillary gas transfer, with linear O2 equilibrium curve, can be very useful to estimate diffusion and perfusion limitations from experimental data.

Altitude↗

Na+/H+ exchange modulates Ca2+ mobilization in human platelets stimulated by ADP and the thromboxane mimetic U 46619.

According to recent observations ADP stimulates platelets via activation of Na+/H+ exchange which increases cytosolic pH (pHi). This event initiates formation of thromboxane A2 (via phospholipase A2) and, thereafter, inositol 1,4,5-trisphosphate (via phospholipase C) which is known to mobilize Ca2+ from intracellular storage sites. We investigated changes in pHi and cytosolic free Ca2+, [Ca2+]i, activating platelets with ADP and the thromboxane mimetic U 46619. We found that ADP (5 microM) increased pHi from 7.15 +/- 0.08 to 7.35 +/- 0.04 (n = 8) in 2'-7'-bis-(carboxyethyl)-5,6-carboxyfluorescein-loaded platelets, whereas thromboxane A2 formation was inhibited by indomethacin. ADP also induced a dose-dependent Ca2+ mobilization in fura2-loaded platelets which again was not affected by indomethacin. [Ca2+]i increased by 54 +/- 10 nM (n = 8) at 1 microM and by 170 +/- 40 nM (n = 7) at 10 microM ADP above the resting value of 76 +/- 12 nM (n = 47). Inhibition of Na+/H+ exchange by ethylisopropylamiloride (EIPA) reduced ADP-induced Ca2+ mobilization by more than 65% in indomethacin-treated platelets. This inhibition could be completely overcome by artificially raising pHi using either NH4Cl or the Na+/H+ ionophore monensin. We found that U 46619 increased pHi by 0.18 +/- 0.05 at 0.1 microM and by 0.29 +/- 0.07 (n = 7) at 1.0 microM above the resting value via an EIPA-sensitive mechanism. In conflict with the proposed role of the Na+/H+ exchange we found that U 46619 raised [Ca2+]i via a mechanism that for more than 50% depended on intact Na+/H+ exchange. Again, artificially elevating pHi restored U 46619-induced Ca2+ mobilization despite the presence of EIPA. Thus, our data show that Na+/H+ exchange is a common step in platelet activation by prostaglandin endoperoxides/thromboxane A2 and ADP and enhances Ca2+ mobilization independently of phospholipase A2 activity.

Benzofurans↗

Counter-current blood flow in tissues: protection against adverse effects.

In hypoxia, the tissue counter-current can thus, by virtue of the Bohr effect, increase tissue Po2 and thus tissue oxygenation. In hyperoxia, on the other hand, the counter-current system, acting as a diffusion shunt, can protect the tissue against adverse O2-toxic effects. It thus appears, that the counter-current system is advantageous for O2 supply to tissues.

Animals↗

Gas exchange in the fish swimbladder.

The fish swimbladder acts as a device to adjust for neutral buoyancy at various depths. High gas pressures, corresponding to the ambient hydrostatic pressure, are encountered, most of which is made up by O2 and N2. To prevent gas loss, the swimbladder wall is made impermeable by guanine crystals in its wall. Gas deposition is made possible by lactic acid production in the swimbladder epithelium, which increases blood gas partial pressures of inert gases (salting-out effect), O2 (Bohr and Root effects) and CO2 (conversion from HCO3-). The hairpin counter-current blood flow in the rete mirabile enhances this partial pressure increase to the tremendous values, up to several 100 atm, encountered in deep sea dwellers. Flow balance in the rete capillaries is found to be crucial, and salt back-diffusion to be advantageous, for the concentrating efficiency in the rete mirabile.

Air Sacs↗

Thrombin-induced cytosolic alkalinization in human platelets occurs without an apparent involvement of HCO3-/Cl- exchange.

We have estimated the changes in cytosolic pH (pHi) that occur when human platelets are stimulated by thrombin. Changes in pHi were estimated (i) from the H+ efflux across the plasma membrane using an extracellular pH electrode and (ii) using an intracellular pH-sensitive fluorescent dye (BCECF). Stimulation of platelets with thrombin (0.5 unit/ml) resulted in an H+ efflux that averaged 7.7 +/- 1.6 mumol/10(11) platelets (means +/- SD) leading to an increase in pHi, from 7.05 +/- 0.04 to 7.45 +/- 0.05. Both H+ efflux and pHi changes were unaffected by 0.1 mM 4,4-diisothiocyanostilbene-2,2 disulphonate (DIDS), 0.1 mM 4'-acetamido 4'-isothiostilbene-2,2'-disulphonic acid (SITS), or 0.5 mM bumetanide, suggesting no involvement of anion transport systems, e.g. an HCO3-/Cl- exchange. Removal of HCO3- or Cl- from the suspending buffer had no effect on the extent of the rise in pHi. After blockade of Na+/H+ exchange by 100 microM ethylisopropylamiloride (EIPA), thrombin induced a decrease in pHi the rate of which averaged 0.39 unit/min in HCO3(-)-containing medium, and 0.57 unit/min in HCO3(-)-free medium. The cytosolic buffer capacity for H+ was determined by the nigericin/NH4Cl technique in BCECF-loaded platelets and averaged 25.3 mmol/(1xpH) in buffer containing 8 mM HCO3-, but only 17.2 mmol/(1xpH) in HCO3(-)-free buffer. The total amount of H+ transferred by Na+/H+ exchange can be estimated from our measurements at 10 mmol/l platelet cytosol in the absence of HCO3- and to 14 mmol/l platelet cytosol in the presence of HCO3-, and is in good agreement with the estimated amount of Na+ uptake by ADP-stimulated platelets.(ABSTRACT TRUNCATED AT 250 WORDS)

4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid↗

Buffering characteristics of eel blood at the extreme conditions in the swimbladder.

CO2 binding in whole blood and true plasma of the eel was estimated by measuring CO2 content and pH in blood aliquots equilibrated with various PCO2 values over a wide range expected to occur in the swimbladder. Bicarbonate concentration, [HCO3-], was calculated using the CO2 solubility coefficient, which was measured to average 50 mumols.L-1.Torr-1 (20 degrees C). Buffer lines of non-bicarbonate buffers were obtained in plots of [HCO3-] against pH, and non-bicarbonate buffer values, beta NB, were obtained by curve fitting. In the pH range 6.6-8.2, the buffer line for oxygenated whole blood was sigmoid, while that for deoxygenated blood increased its slope monotonously with increasing pH. The beta NB for oxygenated blood displayed a maximum of about 8.6 mmol.L-1.pH-1 at pH = 7.4 and dropped down to below 1 mmol.L-1.pH-1 at higher and lower pH. Similar shapes of the buffer lines were obtained in true plasma; the [HCO3-] levels and beta NB values were, however, somewhat higher than in whole blood. These data are useful to assess the back-diffusion of CO2 and HCO3- in the rete mirabile of the fish swimbladder and to estimate the effects CO2 back-diffusion exerts on the counter-current enhancement of O2 in the rete.

Air Sacs↗

CO2 back-diffusion in the rete aids O2 secretion in the swimbladder of the eel.

In order to estimate the relative importance of back-diffusion of O2 and CO2 for their partial pressure enhancement in the swimbladder, we have determined O2 and CO2 partial pressure and content and pH in microsamples collected non-obstructively from the afferent and efferent rete vessels in the European eel. 1. The PO2 increased significantly along the arterial vessels of the rete (from 33 to 303 Torr), with no change in O2 content, suggesting O2 not to be exchanged in the rete counter-current system. 2. A corresponding increase of PCO2 (from 4 to 35 Torr) was accompanied by a significant rise in CO2 content (from 8 to 15 mmol.L-1), suggesting significant CO2 back-diffusion in the rete. 3. Changes in PO2 during passage of blood through the swimbladder epithelium were variable and small, and the PO2 in rete venous blood was similar to that in rete arterial blood, explaining the lack of O2 back-diffusion. 4. Using blood CO2 dissociation data, about 70% of the rise in arterial CO2 content was estimated to derive from diffusion of CO2, the remaining 30% from diffusion of HCO3-, from venous to arterial rete capillaries, or from H+ transport in the opposite direction. The data indicate that CO2 back-diffusion in the rete does not only raise the rete arterial PCO2; it also reduces the O2 capacity (Root effect) and thus enhances the arterial PO2.

Air Sacs↗

Time-variations of pretreatment peripheral blood S + G2/M-phase size determined by flow cytometry in adult acute myeloid leukaemia.

The circadian and seasonal variations of pretreatment proliferative activity of peripheral blood (PB) as PB S + G2/M-phase size was determined by flow cytometry in 61 adult patients with acute myeloid leukaemia (AML). Pretreatment PB S-phase (p less than 0.002), G2 + M-phase (p less than 0.008) and S + G2/M-phase size are statistically correlated to the time of sampling, with the highest phase size at the end of the day. Time-variations of the blast cell count are slightly significant (p = 0.049). Cytological diagnosis-related differences in S + G2/M-phase (p less than 0.003) and white blood cell count (p less than 0.04) time-variations are observed. For all patients, no seasonal variations can be drawn, but in AML 1 (p less than 0.029) and AML 4-5 patients (p less than 0.003), the circadian variations of S + G2/M are affected by the seasons. The present results suggest that time may be taken into account in the monitoring of chemotherapy in acute leukaemia.

Adult↗

Effects of thromboxane on respiration and pulmonary circulation in the cat: role of vagus nerve.

Infusion of stoichiometrically equal quantities of acid and base (neutral acid-base infusion) in the cat elicits pulmonary hypertension and rapid shallow breathing (J. Appl. Physiol. 62: 2362-2370, 1987), and thromboxane A2 (TxA2), released from platelets, is responsible for these effects (Respir. Physiol. 71: 169-183, 1988). To investigate the involvement of vagal afferent fibers in these responses, we reversibly blocked signal conduction in the vagus of the cat by bilaterally cooling the vagus nerves to 1 degree C and measured the cardiorespiratory parameters in response to neutral acid-base infusion and infusion of the TxA2 mimetic U-46619. Vagal cooling before infusion caused tidal volume (VT) to increase and respiratory frequency (fresp) to decrease, whereby total ventilation (VE) was slightly enhanced, but did not affect right ventricular blood pressure (Prv). Infusion of neutral acid-base after vagal cooling prompted Prv to rise, on average from 35 Torr to a peak of 60 Torr, and a similar rise was elicited by infusion of U-46619. However, vagal cooling abolished any effect on VT or fresp of both acid-base and U-46619 infusion. After rewarming the vagus nerves, infusion of U-46619 caused fresp to increase and VT to decrease (rapid shallow breathing) with a concomitant rise in Prv, similar to what had been observed in the earlier studies. Our data suggest that the effects of TxA2 and of its mimetic U-46619 on respiration are mediated by the stimulation of vagal afferent fibers, whereas pulmonary hypertension is unrelated to vagal activity.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗

Activation of Na+/H+ exchange and Ca2+ mobilization start simultaneously in thrombin-stimulated platelets. Evidence that platelet shape change disturbs early rises of BCECF fluorescence which causes an underestimation of actual cytosolic alkalinization.

Although an increase in cytosolic pH (pHi) caused by Na+/H+ exchange enhances Ca2+ mobilization in platelets stimulated by low concentrations of thrombin [Siffert & Akkerman (1987) Nature (London) 325, 456-458], studies using fluorescent indicators for pHi (BCECF) and [Ca2+]i (fura2) suggest that Ca2+ is mobilized while the cytosolic pH decreases. Several lines of evidence indicate that the initial fall in BCECF fluorescence is not due to cytosolic acidification but is caused by a platelet shape change. (1) Pulse stimulation of platelets by successive addition of hirudin (4 unit/ml) and thrombin (0.2 unit/ml) induced a shape change of 43 +/- 8% and a fall in BCECF fluorescence, which both remained unchanged when Na+/H+ exchange was inhibited by ethylisopropylamiloride (EIPA, 100 microM). (2) Increasing the thrombin concentration to 0.4 unit/ml doubled the shape change and the fall in BCECF fluorescence, but again EIPA had no effect on these responses. (3) Treating platelets with 2 microM-ADP induced shape change and a decline in BCECF fluorescence that was unaffected by EIPA. (4) A second addition of thrombin to platelets that had already undergone shape change induced an immediate increase in BCECF fluorescence without a prior decrease. (5) Activation of protein kinase C by 1,2-dioctanoyl-sn-glycerol (DiC8) neither induced shape change nor a decline in BCECF fluorescence; in contrast BCECF fluorescence rapidly increased indicating an immediate cytosolic alkalinization. Concurrent analysis of [Ca2+]i under conditions in which shape change did not interfere with BCECF fluorescence showed that cytosolic alkalinization and Ca2+ mobilization started almost simultaneously. These observations suggest that cytosolic alkalinization is not preceded by a fall in pHi and can support Ca2+ mobilization induced by weak agonists.

Blood Platelets↗

Efficiency of parabronchial gas exchange in deep hypoxia: measurements in the resting duck.

Cardio-respiratory parameters and air sac and blood gases were measured in the unrestrained, unanesthetized duck during exposure to varied levels of inspired hypoxia. As ventilation increased with hypoxia, the gas partial pressures in the air sacs and in arterial blood approached the inspired values, the differences being less than 3 Torr for air sacs and less than 5 Torr for arterial blood. To analyze the relative significance of ventilation, diffusion and perfusion in limiting parabronchial gas exchange, the conductances for ventilation (Gvent), diffusion (Gdiff = O2 diffusing capacity) and perfusion (Gperf) were calculated at all hypoxic levels. With increasing hypoxia, down to PIO2 = 50 Torr, all three conductances increased. Whereas Gvent continued to increase beyond this level, Gdiff remained constant, at about 0.27 mmol.min-1.Torr-1, while Gperf decreased, from a value of 0.22 mmol.min-1.Torr-1 at PIO2 = 50 Torr to 0.12 mmol.min-1.Torr-1 at PIO2 = 30 Torr. This reduction in Gperf may result from a direct hypoxic effect on the heart. Whereas ventilation is the main limiting factor for parabronchial gas exchange at rest down to hypoxia levels of PIO2 = 50 Torr, perfusion becomes the main limiting factor at deeper hypoxia. It is suggested that the higher tolerance of hypoxia exhibited by birds compared to mammals is not due to the higher efficiency of parabronchial compared with alveolar gas exchange, but reflects the ability of birds to tolerate lower arterial PCO2 levels than mammals.

Animals↗

Cardiopulmonary function in exercising bar-headed geese during normoxia and hypoxia.

To investigate possible physiologic mechanisms that allow the bar-headed goose to perform strenuous physical activity when flying at high altitude (e.g., above 9,000 m), we measured cardiopulmonary variables during running exercise (treadmill; 0.6 m.sec-1; 2 degrees incline) while the bird breathed either normoxic (21% O2) or hypoxic (7% O2) gases via a face mask. 1. During normoxic exercise, O2 uptake rate doubled and both ventilation and cardiac output increased. Blood gases and pH in arterial, mixed venous and blood from the leg, however, remained virtually unaltered. 2. Hypoxia at rest stimulated ventilation to rise but not cardiac output. The birds reached a steady state with virtually unaltered O2 uptake. 3. Exercise during hypoxia further stimulated ventilation, resulting in elevated arterial PO2 and O2 content compared to hypoxia at rest. However, O2 uptake increased only slightly, and cardiac output did not rise over the resting hypoxic value. The hyperventilation resulted in respiratory alkalosis and increased CO2 output, with R values being as high as 2.0. 4. It is concluded that neither ventilation nor pulmonary gas transfer were the limiting step in supplying O2 to the working muscles during hypoxic exercise in our experiments. It is more likely that muscle blood flow or diffusion from muscle capillaries to mitochondria, or both, determined the aerobic capacity under these conditions.

Animals↗

Afferent vagal activity during hyperthermic polypnea in the pigeon.

Respiration-modulated activity in afferent vagal fibers was recorded in 10 pigeons during euthermic breathing and thermal panting. Of these fibers, 13 were identified as intra-pulmonary chemoreceptors (IPCs), that increased discharge with diminishing lung gas PCO2, and 13 as mechanoreceptors, that increased firing with lung inflation. Two types of IPC were observed that were distinct by their firing pattern during panting. Phasic IPCs displayed phasic discharge within the respiratory cycle, even at respiratory frequencies (fresp) as high as 400 min-1. Tonic IPC fired tonically and increased their discharge as fresp increased. Several IPCs were silent during euthermic breathing, but discharged tonically as fresp increased with thermal polypnea. Discharge of neither type of IPC was consistently related to PaCO2. Discharge from mechanoreceptors was phasic with respiration, up to values of fresp as high as 350 min-1. However, the average number of impulses per breath decreased as fresp increased. We conclude that discharge from phasic intrapulmonary chemoreceptors and mechanoreceptors may contribute to setting the respiratory pattern during hyperthermic polypnea.

Animals↗

Oxygen transfer kinetics of red blood cells of the turtle Pseudemys scripta elegans.

The kinetics of O2 uptake into, and release from, the red blood cells (RBC) of the turtle Pseudemys scripta elegans were determined with a stopped-flow technique at varied temperature (10-30 degrees C) and pH (7.5-7.9). The results were compared to those obtained for RBC of other vertebrates and related to morphometric and physiological data on gas/blood diffusion in turtle lungs. The O2 transfer conductance of RBC, G, for O2 release into high concentrations of dithionite, considered to represent the best estimate of true RBC transfer conductance for O2 uptake and release, averaged 0.17 +/- 0.01 at 30 degrees C, 0.13 +/- 0.01 at 20 degrees C, 0.09 +/- 0.01 at 10 degrees C (mean +/- SD, in mmol.min-1.Torr-1.(mlRBC)-1). These values are about one half the corresponding value for human RBC, and this difference may be due to the larger size of turtle RBC (volume, 327 microns 3) compared to human RBC (90 microns 3). The temperature dependence of G, Q10 = 1.3 indicates that, as in human RBC, diffusion through aqueous media is the main limiting factor for O2 exchange. Morphometric data on the lungs of Pseudemys scripta suggest that the resistance to O2 transfer by RBC is lower than that offered by the gas-blood barrier. The total apparent transfer resistance to CO, obtained from previous measurements of pulmonary diffusing capacity for CO in the same species, is much higher than that predicted from the combination of RBC O2 kinetics and morphometric data on gas-blood barrier.

Animals↗

Significance of the Bohr effect for tissue oxygenation in a model with counter-current blood flow.

Counter-current arrangement of afferent and efferent blood flow in tissues is commonly considered to be detrimental to tissue oxygenation, since O2 diffusion would shunt O2 away from the tissue. We have investigated the combined effects of counter-current CO2 and O2 exchange in a simple model, paying particular attention to the Bohr effect. We have obtained the following main results. (1) Back-diffusion of CO2 leads to increasing CO2 partial pressure (PCO2) and CO2 content along the afferent vessel. This is enhanced when fixed acid is released by the tissue into the venous blood, e.g. during hypoxia, which leads to a further PCO2 increase therein. (2) The increasing PCO2, with concomitant decrease in pH, in the afferent blood leads to a decrease in blood O2 affinity (Bohr effect) and thus results in increased PO2. (3) The resulting O2 diffusion shunt diminishes the O2 content in afferent blood, but for most conditions its PO2 remains higher than without the Bohr effect. (4) During hypoxia, both the PO2 in blood reaching the tissue (Pta) as well as in that leaving it (Ptv) are significantly elevated above the level without the Bohr effect. Moreover, with fixed acid release both Pta and Ptv for O2 can be higher than the arterial PO2 value. (5) During hyperoxia, O2 diffusion shunt prevents the tissue PO2 levels from increasing to levels that might be regarded as toxic. It is concluded that a diffusion shunt in tissues stabilizes the O2 partial pressure at the tissue when it varies in arterial blood (hypoxia or hyperoxia).

Arteries↗