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Biomedical subjects

P Scheid

Publications and source records attributed to P Scheid.

At least 91 records · Page 5Linked to original sources
PubMed1989

Cyclooxygenase inhibition and effects of hypoxia on pulmonary circulation and gas exchange in anesthetized dogs.

To investigate whether endogenously produced prostanoids are involved in hypoxic pulmonary vasoconstriction, pulmonary hemodynamic and gas exchange parameters and eicosanoid metabolites were measured in 5 anesthetized, artificially ventilated dogs (mean body weight 27 kg). Hypoxia elicited pulmonary vasoconstriction, but blood plasma levels of thromboxane B2 (TXB2) and 6-keto-prostaglandin F 1 alpha (6kPGF1 alpha) (stable metabolites of TXA2 and prostaglandin I2, respectively) remained unchanged. Administration of the cyclooxygenase inhibitor indomethacin blocked the synthesis of prostanoids, so that 6kPGF1 alpha and TXB2 levels decreased to values below the detection level (10 pg.ml-1) both during normoxia or hypoxia, but did not affect pulmonary vascular resistance or the alveolar-arterial PO2 difference (PAi-Pa)O2. The pulmonary vascular bed remained, however, responsive to TXA2 as evidenced by infusion of the TXA2 mimetic, U 46619, which significantly increased the pulmonary vascular resistance and (PAi-Pa)O2. Our data suggest that prostanoids are not involved in eliciting the effects of hypoxia on pulmonary hemodynamics and gas exchange efficiency.

6-Ketoprostaglandin F1 alpha↗
PubMed1989

Water and lactate movement in the swimbladder of the eel, Anguilla anguilla.

Hemoglobin (Hb) and lactate (La) concentrations were measured in small (150 microliters) blood samples collected with micropipettes from the inflow and outflow vessels of the rete mirabile of the eel swimbladder. Hemoglobin was used as a marker of the intravascular space. 1. Hemoglobin concentrations suggest that there was no significant water movement between the arterial and venous capillaries in the rete, but a significant 6% water efflux from the vascular space into the swimbladder epithelium. No significant differences in osmolality were observed between the sites of measurement. 2. Of the lactate present in the blood entering the venous capillaries of the rete, 30% derived from release by the swimbladder epithelium; 38% of the lactate entering the venous capillaries diffused back in the rete tissue into its arterial capillaries. 3. Theoretical models suggest that any water movement in the swimbladder, leading to blood flow mismatch in the rete counter-current system, reduces its efficiency to concentrate inert gases, whereas lactate back-diffusion enhances this efficiency.

Air Sacs↗
PubMed1989

Solute back-diffusion raises the gas concentrating efficiency in counter-current flow.

We have extended the counter-current model of the rete mirabile of the fish swimbladder to include the effects of inert gas secretion into the swimbladder as well as solute back-diffusion in the rete capillaries. (1) Gas secretion attenuates the inert gas concentrating efficiency of the rete, i.e. its ability to produce high inert gas partial pressures in blood at the swimbladder pole. The maximum attainable gas secretion rate depends on the salting-out effect, i.e. on the ratio of solubility in venous and arterial blood of the rete. (2) Solute back-diffusion leads to a significant increase in the concentrating efficiency, and this is due to the salting-out effect produced by the solute when it diffuses back into the arterial capillary blood. This enhancement is particularly prominent when gas and solute permeabilities of the rete vessels are high. (3) Estimates for physiologic parameters in the European eel suggest that lactate back-diffusion may contribute significantly to the gas concentrating efficiency of the rete mirabile.

Air Sacs↗
PubMed1988

Dependence of O2 transfer conductance of red blood cells on cellular dimensions.

To estimate the significance of the dimensions of RBC on O2 transfer, the kinetics of O2 release from RBC into medium containing dithionite (40 mmol/l) was measured, by a stopped-flow technique, for nine different species with varying RBC size (man, llama, vicuna, alpaca, dromedary camel, pygmy goat, domestic hen, muscovy duck and turtle). The observed O2 transfer kinetics were found to be size-dependent, i.e. the O2 transfer conductance of the single RBC, gst, was lower, whereas the specific O2 transfer conductance of packed RBC, Gst, or of whole blood, theta st, was higher for smaller RBC. The ratio of surface area to effective diffusion path length which was found to be about one fourth of the mean cell thickness irrespective of cell size and cell shape, may be considered as the essential morphological factor determining O2 transfer efficiency of the single RBC.

Animals↗
PubMed1988

Acid infusion elicits thromboxane A2-mediated effects on respiration and pulmonary hemodynamics in the cat.

We have recently reported that infusion of stoichiometrically equal quantities of acid and base (neutral acid-base infusion) in the cat resulted in rapid, shallow breathing and in pulmonary hypertension (Orr et al., 1987). To investigate the mechanisms involved in these effects, we have measured in the anesthetized cat thromboxane (TX) B2 and 6-keto-prostaglandin (PG) F1 alpha, the stable metabolites of TXA2 and PGI2, in blood as well as cardiorespiratory parameters in response to neutral acid-base infusion. The first acid-base infusion prompted right ventricular blood pressure (Prv) to rise from 30 to a peak of about 55 mm Hg, with a concomitant rise in the right ventricular TXB2 level from below detection level to over 500 pg/ml. The second or third infusion evoked no (or small) rises in Prv and TXB2, individual values of Prv and TXB2 being tightly correlated. After blockade of TX synthesis by Dazmegrel, no changes were observed even at the first acid-base infusion in either Prv or TXB2. The TXA2 mimetic, U 46,619, caused Prv to rise with no change in TXB2, and this effect was repeatable. Increases were also observed in ventilation, particularly in respiratory rate. We conclude that acid exposure of blood stimulates TX synthesis and release from platelets, which in turn leads to pulmonary hypertension and to hyperventilation. The fact that these effects cannot be repeated within the same animal is due to a lack in TX release but not to a loss of responsiveness of the TX receptors in the lung.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗
PubMed1988

Absence of CO2-sensitive venous chemoreceptors in the cat.

We tested for the presence of CO2-sensitive venous chemoreceptors in anesthetized, paralyzed, artificially ventilated cats (N = 8). Systemic venous PCO2 was elevated (venous CO2 loading) by continuously passing blood withdrawn from the femoral artery (20 ml/min) through an extracorporeal gas exchanger, ventilated with 50% CO2 and 50% O2, and returning this hypercapnic blood to the femoral vein. Respiratory output was assessed by means of the amplitude of the integrated phrenic neurogram. Results of venous CO2 loading were compared to those of airway CO2 loading in which inspired CO2 levels were adjusted to give the same arterial PCO2 (PaCO2) as in venous loading. Despite large differences in mixed venous PCO2 (PvCO2) during venous CO2 loading (PvCO2 = 55 Torr, PaCO2 = 37 Torr) compared to airway CO2 loading (PvCO2 = 45 Torr, PaCO2 = 37 Torr), phrenic output was unchanged. However, phrenic output was elevated 33% when PaCO2 was increased 6-7 Torr by raising inspired CO2 and reduced 50% when PaCO2 was lowered 6-7 Torr by lowering inspired CO2, thereby substantiating the responsiveness of the respiratory control system to changes in PaCO2. The respiratory output response to changes in venous CO2 was also tested at a higher PaCO2 (40 Torr, created by adding 1% CO2 to the inspired air) and, as before, no change in phrenic output occurred when PvCO2 was elevated at a constant PaCO2. These experiments provide direct evidence for the absence of chemoreceptors in the central veins, right heart, and pulmonary arterial system of the cat that would respond to changes in PvCO2.

Animals↗
PubMed1988

Oxygen transfer of red blood cells: experimental data and model analysis.

Kinetics of O2 uptake and release by human red blood cells (RBC) as measured by stopped-flow techniques were simulated using an RBC model shaped as a spheric shell. The O2 transfer mechanisms in this model include diffusion and reaction within the RBC and diffusion and convection in the medium surrounding the RBC. Unknown model parameters were determined by comparing simulations with experimental data. The following conclusions were drawn. (1) Both diffusion and convection contribute to O2 transport in the medium surrounding the RBC, and this transport importantly limits the overall O2 transfer kinetics in stopped-flow experiments. (2) Intraerythrocyte transport mechanisms become predominant in limiting O2 transfer, and can thus be investigated by stopped-flow techniques, only when the perierythrocyte O2 transport resistance is minimized, e.g. by high levels of dithionite in measurements of O2 release from RBC. (3) Intraerythrocyte O2 transfer is shown to be mainly limited by diffusion of O2 and, to a lesser extent, by diffusion of oxyhemoglobin ('facilitated O2 diffusion') and by O2/hemoglobin reaction. The results suggest that diffusion is the main process limiting O2 uptake and release by RBC, the finite reaction kinetics of O2 with hemoglobin exerting a smaller limiting effect.

Erythrocytes↗
PubMed1988

Solubility of nitrogen and argon in eel whole blood and its relationship to pH.

The solubility coefficients (alpha) for the inert gases, nitrogen (N2) and argon (Ar), were measured by mass spectrometry in whole blood of the freshwater-adapted European eel, Anguilla anguilla, at varied pH and at two temperatures, 5 and 15 degrees C. The pH was altered either by varying PCO2 (0.75-75 mmHg; 1 mmHg = 133.3 Pa) or by adding fixed acid (HCl or lactic acid). No dependence of alpha on pH (range 5.5-8.4) or on lactate concentration (range 0.2-25 mmol l-1) was detectable. Average values (+/- S.D.) for alpha (mumol l-1 mmHg-1) were: alpha N2 = 1.25 +/- 0.01, alpha Ar = 2.60 +/- 0.05 at 5 degrees C and alpha N2 = 1.09 +/- 0.03, alpha Ar = 2.12 +/- 0.07 at 15 degrees C. These data yield values for Q10 of 0.87 for nitrogen and 0.82 for argon, and for activation energy, Ea (kJ mol-1 K-1), of -9.2 for nitrogen and -13.4 for argon. The results do not support earlier reports on significant pH dependence of alpha in eel blood and suggest, in contrast, that no fundamental differences exist in respect of inert gas solubility between whole blood of the eel and of other vertebrates.

Adenosine Triphosphate↗
PubMed1987

Inhibition of Na+/H+ exchange reduces Ca2+ mobilization without affecting the initial cleavage of phosphatidylinositol 4,5-bisphosphate in thrombin-stimulated platelets.

Stimulation of human platelets increases cytoplasmic pH (pHi) via activation of Na+/H+ exchange. We have determined the effect of inhibiting Na+/H+ exchange on (i) thrombin-induced Ca2+ mobilization and (ii) turnover of 32P-labelled phospholipids. Blocking Na+/H+ exchange by removal of extracellular Na+ or by ethylisopropylamiloride (EIPA) inhibited Ca2+ mobilization induced by 0.2 U/ml thrombin, whereas increasing pHi by NH4Cl enhanced the thrombin-induced increase in cytosolic free Ca2+. The effect of EIPA was bypassed after increasing pHi by moneasin. The thrombin-induced cleavage of phosphatidylinositol 4,5-bisphosphate (PIP2) was unaffected by treatments that blocked Na+/H+ exchange or increased pHi. It is concluded that activation of Na+/H+ exchange is a prerequisite for Ca2+ mobilization in human platelets but not for the stimulus-induced hydrolysis of PIP2.

Amiloride↗
PubMed1987

Activation of Na+/H+ exchange in human platelets stimulated by thrombin and a phorbol ester.

We have investigated changes in cytoplasmic pH (pHi) in activated human platelets, using the fluorescent probe 2,7-biscarboxyethyl-5(6)-carboxyfluorescein. Stimulation of platelets by thrombin or 12-O-tetradecanoylphorbol 13-acetate increased pHi by about 0.11 pH unit above the resting value. This increase in pHi depended on the presence of external Na+ and was inhibited by ethylisopropylamiloride. The data suggest that protein kinase C mediates Na+/H+ exchange in human platelets.

Amiloride↗
PubMed1987

Effects of temperature on oxygen transfer conductance of human red blood cells.

The influence of temperature (varied from 37 to 7 degrees C; average pH = 7.4) on the kinetics of O2 uptake and release by human red blood cells under stopped-flow conditions was investigated by double-beam spectrophotometry. The kinetics were characterized by the specific transfer conductance for O2, G. The temperature coefficient of G, Q10(G), for O2 uptake averaged 1.17, and activation energy, Ea(G) = 2.9 kcal/mol O2. The average values for O2 release were: Q10(G) = 1.30, and Ea(G) = 4.8 kcal/mol O2. The G values for release of O2 from oxyhaemoglobin solution, Gsol, yielded Q10(Gsol) = 2.06, Ea(Gsol) = 13.4 kcal/mol O2. Comparison of these Q10 and Ea values with those for diffusion of O2 and haemoglobin in aqueous media leads to the conclusion that the kinetics of O2 uptake and release by red blood cells in the stopped-flow condition is mainly limited by diffusion of O2 and haemoglobin in the red cell interior and by diffusion of O2 in the medium, and to a lesser degree by chemical reaction kinetics.

Biological Transport, Active↗
PubMed1987

Respiration and blood gases in the duck exposed to normocapnic and hypercapnic hypoxia.

Cardio-respiratory parameters were measured in the unrestrained, unanesthetized duck by whole body plethysmography during exposure to varied levels of inspired hypoxia without or with (3.7%) CO2. At any level of inspired PO2 (PIO2), ventilation (VE) was larger with CO2 inhalation, leading, for PIO2 greater than 50 Torr, to higher levels of arterial PO2 (PaO2) and O2 content (CaO2). Below PIO2 of 50 Torr, the (PI-Pa)O2 difference without CO2 reached a value as low as 5 Torr which was not diminished by further stimulation of VE by inhaled CO2. Without CO2 inhalation at this deep hypoxic level the ensuing hypoxia-induced respiratory alkalosis was partly compensated by lactacidosis, whereas CO2 inhalation resulted in markedly lower blood pH leading to significantly lower arterial and venous O2 content (Bohr effect). As a result, the deepest level of hypoxia tolerated without CO2 inhalation, 30 Torr, is significantly deeper than that, 36 Torr, tolerated when CO2 is inhaled. The data suggest that a number of factors contribute to the high hypoxia tolerance in birds, e.g. the effectiveness of parabronchial ventilation and the tolerance of low arterial PCO2 levels, whereby part of the lactacidosis is compensated.

Acid-Base Equilibrium↗
PubMed1987

Oxygen transfer conductance of human red blood cells at varied pH and temperature.

The influence of temperature (varied from 37 to 7 degrees C) and of medium pH (varied from 7.7 to 7.1) on the kinetics of O2 uptake and release by human red blood cells (RBC) under stopped-flow conditions was investigated by double-beam spectrophotometry. From the rate of O2 saturation change and the mean effective PO2 difference between the medium and the Hb of RBC, the specific transfer conductance for O2, G, was calculated. The temperature coefficient, Q10, of G for O2 uptake averaged 1.17, activation energy, Ea, 2.6 kcal/mol O2; the average values for O2 release were: Q10 = 1.32, Ea = 4.8 kcal/mol O2. The G value for release of O2 from oxyhemoglobin solution, Gsol, yielded Q10 = 2.25, Ea = 13.5 kcal/mol O2. Comparison of these Q10 and Ea values with those for diffusion of O2 and hemoglobin in aqueous media leads to the conclusion that in the stopped-flow condition the conductance for O2 transfer was mainly limited by diffusion of O2 and hemoglobin in the red cell interior and by diffusion of O2 in the medium, and to a lesser degree by chemical reaction kinetics. This was further supported by the lack of dependence of O2 transfer conductance values on pH.

Adult↗
PubMed1987

Cardiorespiratory changes during HCl infusion unrelated to decreases in circulating blood pH.

To test the hypothesis that infusion of HCl changes blood pressure and respiration independent of decreases in circulating blood pH, an extracorporeal arteriovenous shunt (20 ml/min) between the femoral artery and vein was installed in anesthetized cats. Into this loop, acid (0.25 M HCl) and, approximately 10 cm downstream, base (0.25 M NaOH) could be infused simultaneously. Likewise, either acid or base could be infused individually. Right ventricular (Prv) and arterial (Pa) blood pressure, tidal volume (VT), and respiratory frequency (fresp) were recorded as well as blood gases and pH in arterial, right ventricular, and shunt loop blood at the reentrance into the animal. When HCl and NaOH were infused simultaneously and at equimolar rates (0.2 mmol/min for 10 min), there was a large increase in Prv, with little change or decrease in Pa. Respiratory frequency was increased, but total ventilation was not elevated because of a concomitant fall in VT. The rise in Prv and increase in fresp were transient in that they could only be evoked during the first HCl-NaOH infusion in a given animal. Repetitive infusions of HCl-NaOH into the same animal failed to elicit the response. Similar transient acid effects were evoked when HCl was infused without NaOH but not when NaOH was infused without HCl. During the second and third infusion of HCl, ventilatory responses were elicited that were explainable by stimulation of known chemoreceptors. The transient rise in Prv and fresp evoked by acid infusion might be explained by release of an agent from blood elements at the tip of the HCl infusion catheter, which in turn would constrict pulmonary vessels and influence breathing.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1986

A phorbol ester and 1-oleoyl-2-acetylglycerol induce Na+/H+ exchange in human platelets.

This study aimed at investigating the mechanisms by which stimulation of human platelets results in activation of Na+/H+ exchange. Platelets were suspended in a slightly buffered medium and the stimulus-induced, amiloride-sensitive H+ release, reflecting Na+/H+ exchange, was estimated from changes in the medium pH. H+ release could be evoked by thrombin and by activators of protein kinase C such as 1-oleoyl-2-acetylglycerol (OAG) or 12-O-tetradecanoylphorbol-13-acetate (TPA). Both the thrombin-and the OAG-induced Na+/H+ exchange could be blocked by trifluoperazine, a protein kinase C inhibitor. The thrombin-induced H+ release was also sensitive to increased intracellular cAMP levels, probably due to inhibition of phospholipase C activation, whereas the OAG-induced activation of Na+/H+ exchange was unaffected. Our data suggest that activation of Na+/H+ exchange is mediated by protein kinase C.

Alprostadil↗