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Susan R. Hopkins - One of the best experts on this subject based on the ideXlab platform.

  • exercise induced arterial hypoxemia the role of ventilation perfusion inequality and pulmonary Diffusion Limitation
    Advances in Experimental Medicine and Biology, 2006
    Co-Authors: Susan R. Hopkins
    Abstract:

    Many apparently healthy individuals experience pulmonary gas exchange Limitations during exercise, and the term “exercise induced arterial hypoxemia” (EIAH) has been used to describe the increase in alveolar-arterial difference for oxygen (AaDO2), which combined with a minimal alveolar hyperventilatory response, results in a reduction in arterial PO2. Despite more than two decades of research, the mechanisms of pulmonary gas exchange Limitations during exercise are still debated. Using data in 166 healthy normal subjects collated from several previously published studies it can be shown that ∼20% of the variation in PaO2 between individuals can be explained on the basis of variations in alveolar ventilation, whereas variations in AaDO2 explain ∼80%. Using multiple inert gas data the relative contributions of ventilation-perfusion (“\( \dot V_A /\dot Q \) ”) inequality and Diffusion Limitation to the AaDO2 can be assessed. During maximal exercise, both in individuals with minimal (AaDO2 < 20 Torr, x = 13±5, means ±SD, n = 35) and moderate to severe (AaDO2= 25–40 Torr, x = 33±6, n = 20) gas exchange Limitations, \( \dot V_A /\dot Q \) inequality is an important contributor to the AaDO2. However, in subjects with minimal gas exchange impairment, \( \dot V_A /\dot Q \) inequality accounts for virtually all of the AaDO2 (12±6 Torr), whereas in subjects with moderate to severe gas exchange impairment it accounts for less than 50% of the AaDO2 (15±6 Torr). Using this framework, the difficulties associated with unraveling the mechanisms of pulmonary gas exchange Limitations during exercise are explored, and current data discussed.

  • Pulmonary transit time and Diffusion Limitation during heavy exercise in athletes
    Respiration physiology, 1996
    Co-Authors: Susan R. Hopkins, Allan S. Belzberg, Barry Wiggs, Donald C. Mckenzie
    Abstract:

    To investigate relationships between pulmonary transit times (PTT) and pulmonary Diffusion Limitation during exercise, 10 high aerobic capacity athletes (VO2max = 5.15 +/- 0.52 l.min-1) who had multiple inert gas elimination analysis evidence suggestive of Diffusion disequilibrium were studied at rest and maximal exercise. Diffusing capacity for oxygen (DLO2) was calculated from the inert gas data. First pass radionuclide angiography was performed using 99mTechnecium labeled erythrocytes and whole lung PTT and pulmonary blood volume (PBV) were calculated. PTT decreased from 9.32 +/- 1.41 sec at rest, to 2.91 +/- 0.30 sec during exercise and was correlated with Diffusion Limitation suggested by the inert gases (r = -0.58, P < 0.05). PBV increased during exercise to over 25% of whole blood volume and correlated with DLO2 (r = 0.82, P < 0.01). These data suggest that Diffusion Limitation is related to shortened PTT in athletes and that maximal recruitment of PBV may defend against Diffusion Limitation.

  • pulmonary gas exchange during exercise in athletes i ventilation perfusion mismatch and Diffusion Limitation
    Journal of Applied Physiology, 1994
    Co-Authors: Susan R. Hopkins, Donald C. Mckenzie, Robert B Schoene, Robb W Glenny, H T Robertson
    Abstract:

    To investigate pulmonary gas exchange during exercise in athletes, 10 high aerobic capacity athletes (maximal aerobic capacity = 5.15 +/- 0.52 l/min) underwent testing on a cycle ergometer at rest, 150 W, 300 W, and maximal exercise (372 +/- 22 W) while trace amounts of six inert gases were infused intravenously. Arterial blood samples, mixed expired gas samples, and metabolic data were obtained. Indexes of ventilation-perfusion (VA/Q) mismatch were calculated by the multiple inert gas elimination technique. The alveolar-arterial difference for O2 (AaDO2) was predicted from the inert gas model on the basis of the calculated VA/Q mismatch. VA/Q heterogeneity increased significantly with exercise and was predicted to increase the AaDO2 by > 17 Torr during heavy and maximal exercise. The observed AaDO2 increased significantly more than that predicted by the inert gas technique during maximal exercise (10 +/- 10 Torr). These data suggest that this population develops Diffusion Limitation during maximal exercise, but VA/Q mismatch is the most important contributor (> 60%) to the wide AaDO2 observed.

Johannes Piiper - One of the best experts on this subject based on the ideXlab platform.

  • oxygen supply to exercising muscle roles of Diffusion Limitation and heterogeneity of blood flow
    Advances in Experimental Medicine and Biology, 1994
    Co-Authors: Johannes Piiper
    Abstract:

    In maximum O2 uptake exercise, the O2 uptake is in many cases probably limited by O2 availability which is determined by blood flow and its distribution, by arterial O2 content and partial pressure (PO2), and by blood/tissue Diffusion conditions. In this report it is attempted to analyze the role of these factors, on the basis of model calculations and experimental data.

  • Diffusion perfusion inhomogeneity and alveolar arterial o2 Diffusion Limitation theory
    Respiration Physiology, 1992
    Co-Authors: Johannes Piiper
    Abstract:

    Abstract Unequal distribution of pulmonary O2 diffusing capacity (D) to pulmonary blood flow (Q)(D/Q heterogeneity) leads to decreased alveolar O2 exchange efficacy. It is shown on simple models that the effect increases with increasing amount of inequality and with increasing value of the equilibration index, D/(Qβ)(β, increment in blood O2 content per partial pressure increment). This inhomogeneity effect, if not taken into account, leads to spurious increases of D in hypoxia and with elevated O2 uptake.

  • Diffusion Limitation of oxygen in heterogeneous lung and tissue models.
    Advances in experimental medicine and biology, 1992
    Co-Authors: Johannes Piiper
    Abstract:

    In the analysis of gas exchange in lungs models have been developed to distinguish Diffusion Limitation from other mechanisms producing gas exchange inefficiency such as ventilation/perfusion (VA/Q) inhomogeneity and shunt. It will be attempted to apply similar models to describe and explain gas exchange in tissues, in particular to establish the role played by Diffusion Limitation in O2 supply to exercising muscle.

  • Diffusion Limitation of O2 supply to tissue in homogeneous and heterogeneous models.
    Respiration physiology, 1991
    Co-Authors: Johannes Piiper, Peter Scheid
    Abstract:

    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 PPO2 >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:√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.

Burtron H. Davis - One of the best experts on this subject based on the ideXlab platform.

H T Robertson - One of the best experts on this subject based on the ideXlab platform.

  • pulmonary gas exchange during exercise in athletes i ventilation perfusion mismatch and Diffusion Limitation
    Journal of Applied Physiology, 1994
    Co-Authors: Susan R. Hopkins, Donald C. Mckenzie, Robert B Schoene, Robb W Glenny, H T Robertson
    Abstract:

    To investigate pulmonary gas exchange during exercise in athletes, 10 high aerobic capacity athletes (maximal aerobic capacity = 5.15 +/- 0.52 l/min) underwent testing on a cycle ergometer at rest, 150 W, 300 W, and maximal exercise (372 +/- 22 W) while trace amounts of six inert gases were infused intravenously. Arterial blood samples, mixed expired gas samples, and metabolic data were obtained. Indexes of ventilation-perfusion (VA/Q) mismatch were calculated by the multiple inert gas elimination technique. The alveolar-arterial difference for O2 (AaDO2) was predicted from the inert gas model on the basis of the calculated VA/Q mismatch. VA/Q heterogeneity increased significantly with exercise and was predicted to increase the AaDO2 by > 17 Torr during heavy and maximal exercise. The observed AaDO2 increased significantly more than that predicted by the inert gas technique during maximal exercise (10 +/- 10 Torr). These data suggest that this population develops Diffusion Limitation during maximal exercise, but VA/Q mismatch is the most important contributor (> 60%) to the wide AaDO2 observed.

Anja E.m. Janssen - One of the best experts on this subject based on the ideXlab platform.

  • Modelling of the enzymatic kinetically controlled synthesis of cephalexin: influence of Diffusion Limitation.
    Biotechnology and bioengineering, 2002
    Co-Authors: C.g.p.h. Schroën, C.b. Fretz, V.h. Debruin, W. Berendsen, Harold Monro Moody, E.c. Roos, J.l. Vanroon, P.j. Kroon, M. Strubel, Anja E.m. Janssen
    Abstract:

    In this study the influence of Diffusion Limitation on enzymatic kinetically controlled cephalexin synthesis from phenylglycine amide and 7-aminodeacetoxycephalosporinic acid (7-ADCA) was investigated systematically. It was found that if Diffusion Limitation occurred, both the synthesis/hydrolysis ratio (S/H ratio) and the yield decreased, resulting in lower product and higher by-product concentrations. The effect of pH, enzyme loading, and temperature was investigated, their influence on the course of the reaction was evaluated, and eventually Diffusion Limitation was minimised. It was found that at pH 7 the effect of Diffusion Limitation was eminent; the difference in S/H ratio and yield between free and immobilised enzyme was considerable. At lower pH, the influence of Diffusion Limitation was minimal. At low temperature, high yields and S/H ratios were found for all enzymes tested because the hydrolysis reactions were suppressed and the synthesis reaction was hardly influenced by temperature. The enzyme loading influenced the S/H ratio and yield, as expected for Diffusion-limited particles. For Assemblase 3750? (the number refers to the degree of enzyme loading), it was proven that both cephalexin synthesis and hydrolysis were Diffusion limited. For Assemblase 7500?, which carries double the enzyme load of Assemblase 3750?, these reactions were also proven to be Diffusion limited, together with the binding-step of the substrate phenylglycine amide to the enzyme. For an actual process, the effects of Diffusion Limitation should preferably be minimised. This can be achieved at low temperature, low pH, and high substrate concentrations. An optimum in S/H ratio and yield was found at pH 7.5 and low temperature, where a relatively low reaction pH can be combined with a relatively high solubility of 7-ADCA. When comparing the different enzymes at these conditions, the free enzyme gave slightly better results than both immobilised biocatalysts, but the effect of Diffusion Limitation was minimal

  • Cephalexin synthesis by immobilised penicillin G acylase under non-isothermal conditions: reduction of Diffusion Limitation
    Journal of Molecular Catalysis B-enzymatic, 2001
    Co-Authors: C.g.p.h. Schroën, Anja E.m. Janssen, M.s. Mohy Eldin, G.d Mita, Johannes Tramper
    Abstract:

    Abstract The effect of thermodialysis on the enzymatic kinetic synthesis of the antibiotic cephalexin was investigated. As reference points, two existing models for an immobilised enzyme (Assemblase ® ) and for the free enzyme were used. For Assemblase ® , it is known that Diffusion Limitation occurs and that therefore considerably more of the undesired side-product phenylglycine is formed. The enzyme was immobilised on a membrane, and under isothermal conditions (293 K) the course of the reaction resembled that of the Assemblase ® enzyme. However, if a temperature gradient was applied across the membrane, with an average temperature of 293 K for the enzyme, than the course of the reaction changed. For large temperature gradients (30° and more), the course of the reaction resembled that of free enzyme. Thermodialysis enhances mass transfer across the membrane and therewith reduces Diffusion Limitations in the immobilised enzyme on the membrane. The stability of the immobilised enzyme is such that the reactor can be re-used repeatedly. This, together with the positive effect of the temperature gradient on the course of the reaction, makes thermodialysis an interesting new technique that has potential to be applied on a larger scale if the membrane surface area per volume of reactor can be improved.