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P Scheid

Publications and source records attributed to P Scheid.

At least 109 records · Page 6Linked to original sources

Inert gas wash-out from tissue: model analysis.

Model simulations on variously arranged two-compartment models are performed to provide a basis for interpreting the observed non-monoexponential (or non-linear logarithmic) wash-out time courses of inert gases from tissue. The variables considered are: blood flow, tissue volume, solubility of gas in tissue and blood, and diffusive conductances (diffusing capacities) for tissue/blood gas transfer and for gas transfer between tissue compartments. The wash-out is studied in terms of both mean tissue partial pressure and effluent venous blood partial pressure. Diffusion limitation within a tissue-blood capillary unit is shown to produce logarithmic wash-out rates which increase or decrease during wash-out, depending on the functional structure of the unit. On the other hand, in a system consisting of dissimilar tissue-blood capillary units arranged in parallel, the logarithmic wash-out rate decreases with wash-out time. It is shown that the conventional analysis of nonlinear logarithmic wash-out may overestimate or underestimate tissue perfusion or the extent of its inhomogeneity.

Animals↗

Effects of altering dead space volume on respiration and air sac gases in geese.

Dead space volume (VD) was altered in spontaneously breathing, anesthetized geese from values far above (about 115 ml) to those far below (about 3 ml) the normal VD (approximately 40 ml). Respiratory gases were measured in cranial (CrS) and caudal air sacs (CdS) and in blood. The major findings were as follows: Ventilation increased linearly with VD, by increases in tidal volume (VT) at constant breathing rate (fresp); effective parabronchial ventilation, (VT-VD) X fresp, remained constant and so did arterial blood gases. No changes occurred in CrS gas composition. CdS PCO2 declined with decreasing VD, and the respiratory exchange ratio increased, reaching values above unity at the lowest VD. The gas composition in CrS, and particularly its relation to end-expired gas composition, is in agreement with current models of the gas flow pattern in the avian lung. The PCO2 values in CdS are higher than expected by simple models, e.g. by dead space re-inhalation. Neopulmonic gas exchange and incomplete gas mixing are suggested to contribute significantly to the gas composition of CdS.

Air Sacs↗

Cross-sectional PO2 distributions in Krogh cylinder and solid cylinder models.

Radial profiles, gradients and frequency distributions of PO2 are calculated for two cylindrical tissue models with uniform O2 diffusion properties and O2 consumption: Krogh's cylinder with O2 supplied from a central capillary (model A), and a solid cylinder with O2 supplied from the outer surface (model B). Because the O2 diffusion flux is divergent in model A, and convergent in model B, the PO2 gradient flattens with increasing distance from the supplying surface more rapidly in model A than in model B. In model A, the frequency distribution of PO2 with respect to unit cross-sectional area is highly asymmetric, being skewed to low PO2, whereas it is uniform in model B. Model A is applicable to parallel capillaries uniformly distributed across tissue cross-section. For Model B a large number of capillaries surrounding a cylindrical structure is required. Model A appears to be much more adequate than model B to describe the normal morphometry in skeletal muscle (capillary number/fiber number ratio of about 2, capillary-to-muscle fiber radius ratio of about 0.1). The experimental finding of relatively low PO2 and small PO2 gradients within muscle fiber cross-sections is in agreement with both models, but agrees better with model A than with model B.

Capillaries↗

Model for analysis of counter-current gas transfer in fish gills.

The validity of previously used simplified models for the analysis of gas transfer in fish gills was tested using an integrated model which includes water flow and blood flow in counter-current arrangement. The model accounts for the resistance to diffusion of O2 both in the water-blood barrier and in the interlamellar water, which is assumed to flow with a parabolic velocity profile between the secondary lamellae. The O2 diffusing capacity (transfer factor) for this model (Dint) was compared to that (Dm + w) calculated from the diffusing capacity of the water-blood barrier (Dm), and from the effective diffusive conductance of the parabolically streaming interlamellar water (Dw) as 1/Dm + w = 1/Dm + 1/Dw. These diffusing capacities were compared with that (Dadd) calculated from Dm and diffusing capacity of a water layer of 1/4 thickness of the interlamellar space (Dw) as 1/Dadd = 1/Dm + 1/Dw. Calculations with morphometric and gas exchange parameters in the elasmobranch Scyliorhinus stellaris reveal the following features: (1) In physiological conditions, Dm + w and Dint are similar to within 10%, but Dint is always higher. (2) Dint and Dm + w increase with increasing ventilation; Dint increases with decreasing perfusion, while Dm + w remains constant. (3) Both Dint and Dm + w agree reasonably well with Dadd. In other anatomical and physiological conditions, particularly for relatively high Dm, Dw, and Dw and high ventilation, greater discrepancies between Dint and Dm + w may occur but Dm + w appears to represent a reasonable approximation of the effective O2 diffusing capacity, which is best modelled as Dint.

Animals↗

Kinetics of oxygen uptake and release by red blood cells of chicken and duck.

The specific conductance (G) for O2 transfer by red blood cells (RBCs) of chicken and muscovy duck was measured using the experimental (stopped-flow) and analytical techniques (RBC model) previously applied to human RBC (Yamaguchi, Nguyen Phu, Scheid & Piiper, 1985). Avian RBCs behaved similarly to human RBCs: G values were of similar magnitude; G for O2 uptake decreased with time and increasing O2 saturation; G for O2 release at high levels of dithionite decreased slightly with decreasing O2 saturation; G for O2 release was higher than G for O2 uptake. The deoxygenation kinetics of oxyhaemoglobin in solution was similar for both avian species. The G measured for O2 release at high dithionite concentration, considered to represent a good approximation to intra-erythrocyte O2 diffusion conductance, averaged (in mmol min-1 Torr-1 ml-1 RBC) 0.33 for chicken and 0.25 for duck (at 41 degrees C, pH of the suspension = 7.5, O2 saturation range 0.4-0.8). These species differences can be explained by differences in cell size, the RBC volume averaging 104 micron3 in the chicken and 155 micron3 in the duck. Compared with human RBCs, the G estimates for avian RBCs are somewhat smaller than would be predicted from size differences, which can be explained by the discoid shape of mammalian RBCs which constitutes an advantage compared with the ovoid avian RBC.

Animals↗

Kinetics of O2 uptake and release by red cells in stopped-flow apparatus: effects of unstirred layer.

Using a stopped-flow apparatus, measurements were made of the velocity of uptake and release of oxygen by red cells of man, sheep and goat, three species of widely differing red cell size. The results were used to calculate resistances to O2 uptake provided by: (1) any unstirred layer (USL) outside the cells; (2) the cell membrane; and (3) the cell substance, in which the process of simultaneous diffusion and chemical reaction occurs. For O2 release, the USL was virtually abolished by using sufficient dithionite in the reactant buffer for it to diffuse up to the cell membrane and mop up O2 as it passes out of the cell. Hence, differences in the rate of O2 uptake and release allowed estimation of the resistance and thickness of the USL. Its thickness in the three species was between 0.7 and 0.9 micron; it provided at least 70% of the resistance to O2 uptake located outside the cell interior (cell membrane plus USL). Existence of the USL slows the uptake of O2 in the stopped-flow apparatus by a factor of at least 1.8 to 2.0.

2,3-Diphosphoglycerate↗

Oxygen binding in blood of Xenopus laevis (Amphibia) and evidence against Root effect.

Blood oxygen binding was examined in the amphibian, Xenopus laevis, with the particular aim of determining whether the O2 capacity is diminished when blood pH is lowered, which is known as the Root effect in blood of some fishes. Hemoglobin-bound O2 concentration, [O2Hb], was determined by the Lex-O2-Con technique, and both total hemoglobin, [Hb]tot, and Met-hemoglobin, [MetHb], contents were measured spectrophotometrically. From these measurements were calculated the oxygen capacity, O2cap, and the content of active hemoglobin, [Hb]act, i.e. the difference between [Hb]tot and [MetHb]. The main finding was the independence of the ratio of O2cap/[Hb]act on pH, when differences between samples in [Hb]tot and the presence of MetHb, which was particularly pronounced at low pH, where properly accounted for. It is concluded that the Root effect does not exist in blood of the amphibian Xenopus laevis.

Animals↗

Effects of inhibiting carbonic anhydrase on isometric contraction of frog skeletal muscle.

Carbonic anhydrase (CA) activity was determined in a homogenate of frog skeletal muscle by measuring the kinetics of CO2 hydration in a pH stopped-flow apparatus. The results suggest that frog skeletal muscle contains a high-activity CA with properties similar to those of the isoenzyme CA II found in white skeletal muscle tissue of the rabbit. In an attempt to assess the functional significance of CA in skeletal muscle, the maximal isometric force of frog gastrocnemius muscle was measured in response to direct or indirect (ischiadic nerve) single-pulse electrical stimulation before (control) and after exposing the muscle to various concentrations of the specific carbonic anhydrase inhibitors, ethoxzolamide, acetazolamide, and methazolamide. In the range of ethoxzolamide concentration between 10(-9) and 10(-6) M, maximal isometric force with indirect supramaximal stimulation declined progressively with inhibitor concentration to less than 10% of the control value. Acetazolamide and methazolamide were less effective in that concentrations of above 10(-4) M were necessary to inhibit maximum isometric force by 50%. Even at the highest ethoxzolamide concentration used (10(-6) M), no effect was observed either on the amplitude of the compound nerve action potential or on the conduction velocity of group I fibres in the ischiadic nerve, suggesting that ethoxzolamide did not affect the mechanisms responsible for spike generation or conduction in the motor fibres. With direct supramaximal stimulation of the gastrocnemius muscle, no effects on maximal isometric force were observed of CA inhibition by any of the inhibitors used. The results suggest that CA acts on the neuromuscular transmission. The exact site and mechanism of action are unknown.

Acetazolamide↗

Kinetics of O2 uptake and release by human erythrocytes studied by a stopped-flow technique.

The kinetics of O2 uptake into and release from human erythrocytes was investigated at 37 degrees C by a stopped-flow technique. From the time course of O2 saturation (SO2) change a specific transfer conductance of erythrocytes for O2 (GO2) was calculated. The following results were obtained: 1) GO2 decreased in the course of O2 uptake, but initial GO2 was nearly independent of SO2 at which uptake started; 2) addition of albumin to the medium reduced GO2; 3) increasing dithionite concentration in the medium in O2-release experiments progressively enhanced GO2, which became virtually constant for nearly the entire course of release; and 4) O2 uptake and O2 release (without dithoite) in the same SO2 range yielded very similar GO2. These results suggested that O2 uptake and release were importantly limited by diffusion through the external medium and that in the SO2 range between 0.3 and 0.8, chemical reaction exerted little limiting effect. Since O2 release at the highest dithionite concentration (40 mmol/l) appeared to be virtually unlimited by external diffusion, GO2 measured under these conditions, averaging 8.7 ml X min-1 X Torr-1 X ml erythrocytes-1, was considered to mainly reflect intracellular diffusion limitation. The corresponding specific transfer conductance for O2 transfer in whole blood (hematocrit, 0.45) is 3.9 ml X min-1 X Torr-1 X ml blood-1.

Adult↗

Evidence for a role of NA+/H+ exchange in platelets activated with calcium-ionophore A 23187.

We have investigated the release of protons from human platelets and platelet aggregation induced by the calcium ionophore, A 23187. Addition of the ionophore to suspensions of washed platelets resulted in fast liberation of H+. In the presence of 0.2 mM amiloride, a potent inhibitor of Na+/H+ countertransport, the amount of protons liberated was decreased by 50% and was further reduced to about 10% by 1 mM amiloride. Similar inhibition of H+-release was observed after decreasing Na+ in the incubation medium. Both results suggest that increasing internal Ca2+ by the ionophore induces Na+/H+ exchange in human platelets. Platelet aggregation could be induced by adding the ionophore to the platelet suspension. This aggregation was inhibited by amiloride, at least when induced by low ionophore concentrations. The results suggest that stimulation of Na+/H+ exchange, and the concomitant increase in intraplatelet pH, are important mechanisms in platelet activation.

Amiloride↗

Thrombin stimulates Na+-H+ exchange across the human platelet plasma membrane.

We have investigated the release of protons from thrombin-stimulated platelets. Addition of thrombin to suspensions of washed platelets resulted in fast liberation of H+. In the presence of 0.1 mM amiloride, a potent inhibitor of the Na+/H+ transport system, the amount of protons liberated was decreased by about 50%, and was further reduced to about 15% by 1 mM amiloride. Similar inhibition of H+ release was observed after Na+ in the incubating medium had been replaced by choline. We conclude that one of the earliest events in thrombin-stimulated platelets consists of the activation of an Na+/H+ countertransport, which leads to an increase in intracellular pH.

Amiloride↗

Dependence of O2 uptake on tissue Po2: experiments in intact excised rat skeletal muscle.

Oxygen uptake (M) at different surface O2 pressures (Po) was measured in intact, excised rat skeletal muscle suspended in the gas phase. Above a critical value of Po(Pc), M was apparently independent of Po; below Pc, M declined in close proportion to the square root of Po. This experimental relationship was compared with predictions based on the model of Warburg (1923) which assumes the tissue to be homogeneous in respect of its metabolic rate, diffusivity and geometry. The good agreement between the Warburg model and the experimental values suggests that the assumptions underlying this model are justified.

Animals↗

Elements for modeling inert gas washout from heterogeneous tissues.

Inert gas washout from tissue may be analyzed using Krogh's cylinder or a simplified model thereof, represented by a series arrangement of compartments. In particular with limited axial diffusion in tissue, washout from this model is multi-exponential, the rate of washout accelerating with time. To explain the experimentally observed multicomponent washout, in which washout retards with time, heterogeneity of flow and/or diffusing capacity to volume is required, either in series or in parallel compartments. While there appears to be a structural basis for both types of heterogeneity, parallel and series, a distinction between both on the basis of washout curves alone is impossible.

Animals↗

Dual role of diffusion in tissue gas exchange: blood-tissue equilibration and diffusion shunt.

The role of diffusion in inert gas washout from tissue is investigated using simple mathematical models incorporating diffusive blood-tissue equilibration and diffusion shunt due to diffusive gas transfer between precapillary and postcapillary vessels with counter-current blood flow. With increasing diffusivity blood-tissue equilibration is improved, but simultaneously the diffusion shunt by veno-arterial back diffusion is increased. Similarly, with decreasing blood flow, the extent of diffusion limitation in blood-tissue transfer is diminished, but at the same time veno-arterial diffusive shunting is enhanced. Diffusion shunt slows inert gas washout (local tissue clearance) and thus, if not taken into account, leads to an underestimation of capillary blood flow calculated from the washout rate constant. Diffusion shunting of O2 diminishes the efficacy of blood-tissue transfer, but its extent is predicted to be smaller compared to that for inert gases, because the chemical combination of O2 in blood decreases diffusive shunting.

Animals↗

Effects of increasing metabolism by 2,4-dinitrophenol on respiration and pulmonary gas exchange in the duck.

The effects of pharmacologically elevated metabolism on respiration and parabronchial gas exchange were studied in the anesthetized, spontaneously breathing duck using 2,4-dinitrophenol (DNP), injected in successive single doses of 1.2-2.5 mg per kg body mass. Oxygen uptake, MO2, increased with the cumulative amount of DNP, reaching a sevenfold resting level at the highest DNP level tolerated, 15 mg/kg. Ventilation increased nearly as much as MO2, mainly by an increase in respiratory frequency, fresp. Cardiac output increased somewhat less than MO2, mediated by increases in both cardiac frequency and stroke volume. Arterial blood-gases showed little change; however, mixed venous PO2 dropped significantly, and PCO2 increased significantly, with stimulated metabolism. Pulmonary diffusing capacity, DO2, showed a significant rise with MO2, beyond that expected from a reduction of functional lung heterogeneity. The results show that pharmacological stimulation of metabolism can evoke responses in the respiratory and circulatory systems that are comparable to those observed with exercise. The mechanism by which parabronchial diffusing capacity increases during elevated metabolism remains to be investigated.

2,4-Dinitrophenol↗

Dual role of diffusion in tissue gas exchange: blood-tissue equilibration and diffusion shunt.

The role of diffusion in tissue gas exchange is investigated using a simple mathematical model which incorporates both tissue-blood equilibration and gas transfer between arterial and venous vessels with counter-current flow, leading to 'diffusion shunt'. Both increasing the diffusion coefficient of the gas considered or decreasing the blood flow results in two antagonistic effects: (i) improvement of blood/tissue equilibration, (ii) increase in extent of diffusion shunt. The diffusion shunt retards inert gas wash-out (local tissue clearance) and leads thus, if not taken into account, to an underestimation of capillary blood flow calculated from the wash-out rate constant. For O2 (and CO2) the diffusion shunt reduces the efficacy of blood/tissue transfer, but its extent is expected to be only moderate because of the chemical combination of these gases in blood.

Diffusion↗

Gas concentration profiles along airways of dog lungs during high-frequency ventilation.

Following equilibration with inert gases (He and SF6), dog lungs were partially washed out, either by high-frequency ventilation (HFV) or by conventional mechanical ventilation (CMV), to varied inert gas clearance levels, at which expirograms were recorded by mass spectrometry. Relative alveolar slopes were distinctly positive for HFV and tended to increase with lung clearance; they were, however, smaller than those of CMV and were smaller for He than for SF6 during both ventilatory modes. Fowler dead space was smaller for HFV than for CMV, with significant differences between test gases only during CMV. Plots of concentration against linear distance between measuring site and alveolar region showed that most of the total concentration drop during HFV occurred, with nearly linear slope, along the endotracheal tube and the upper airways, with no difference between He and SF6. In the alveolar region, on the other hand, relative concentration gradients were similar for HFV and CMV, both showing separation of He and SF6. The data suggest that gas transport in the upper airways during HFV is not diffusion limited. Gas mixing in alveolar regions, although more complete for HFV than for CMV, is limited by diffusion; however, this incomplete gas mixing does not appreciably limit overall gas transport during HFV.

Animals↗

Root effect induced by CO2 and by fixed acid in the blood of the eel, Anguilla anguilla.

The decrease in O2 capacity with decreasing pH (Root effect) was studied in eel blood in which pH was varied in the range 5 to 9 both by addition of acid or base (fixed-acid Root effect) and by varying PCO2 (CO2 Root effect). Hemoglobin-bound oxygen was independent of PO2 above 150 Torr and was thus referred to as O2 capacity (O2cap). At pH below 8.5, O2cap decreased sigmoidally with pH to attain, below a pH of 6.0, a value which, at 15 degrees C, averaged about 48% of the maximum O2cap, measured above pH 8.5. At 25 degrees C, this reduction was even more pronounced. For pH above about 6.5 the decline in O2cap was independent of whether the pH was diminished by CO2 or by fixed acid. Below pH 6.5, however, the CO2 Root effect exceeded the fixed-acid Root effect. Below pH of 7.5, the buffer value of true plasma increased with declining pH and attained a negative value in the range where CO2 exerted a specific action on the Root effect.

Acids↗