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Biomedical subjects

G Thews

Publications and source records attributed to G Thews.

At least 19 recordsLinked to original sources

Theoretical analysis of factors influencing recovery of ventilation distributions from inert gas washout data.

A method is presented that allows to calculate distributions of ventilation from measured time courses of inert gas washout. In the mathematical description of the washout process a discontinuous algorithm is applied: For each individual breath inspiratory and expiratory tidal volumes, endexpiratory alveolar volume, and dead space inspiration are taken into account. Furthermore, volume reduction of the alveolar gas according to the gas exchange ratio is considered. Commonly in ventilation analysis, the specific ventilation serves as abscissa of the density of the ventilation distribution. As at a given location the specific ventilation changes with varying tidal volumes even if the distribution pattern of the ventilation amongst the lung remains unchanged, the normalized specific ventilation is newly introduced instead. This quantity is defined to be the ratio of regional alveolar ventilation and regional endexpiratory alveolar volume divided by the total alveolar ventilation. The normalized specific ventilation reflects the distribution of the ventilation independently of variations in tidal volume and respiratory frequency. Furthermore, it allows direct comparison of ventilation distributions that are determined at varying alveolar ventilations. Ventilation distributions are approximated by the transformed beta distribution which is parameterized by its mean, variance, and skewness. In order to evaluate simplifications introduced in former studies and to quantify their effects on the resulting ventilation distributions, washout time courses are generated in a computer simulation from the comprehensive discontinuous algorithm and are used to recover ventilation distributions by means of accordingly simplified algorithms. Furthermore, the influence of errors that may occur in the measurement of tidal volumes are assessed. The results of these studies are summarized as follows: Serious errors are introduced in the recovered distributions if ventilation is modelled as a continuous process and if physiological variations in tidal volumes or endexpiratory alveolar volumes or dead space inspiration are neglected. Modelling the entire dead space as common dead space or as local dead space only, entails significant errors as well. Statistical errors of 2% in the measured volumes practically do not have any impacts on the recovered distributions whereas systematic errors significantly deteriorate the results. In conclusion, in ventilation analysis it is essential to apply a discontinuous description of the inert gas washout process that accounts for dead space inspiration and variations in the above mentioned quantities. In addition it is important to obtain all measured values with the highest achievable precision.

Computer Simulation↗

Role of geometry and anisotropic diffusion for modelling PO2 profiles in working red muscle.

A 3-dimensional analytical model of O2 diffusion in heavily working muscle is proposed which considers anisotropic, myoglobin (Mb)-facilitated O2 diffusion inside the muscle fiber and a carrier-free layer separating erythrocytes and fiber. The model is used to study the effects of some commonly applied simplifying assumptions (reduced dimensionality, neglected anisotropy) on the resulting PO2 distributions: (1) In order not to underestimate PO2 drops near erythrocytes, modelling O2 transport in 3 dimensions is important. (2) For a capillary-to-fiber ratio of 1, the results from the 2-dimensional version of the present model and from a Krogh-type model which incorporates a carrier-free layer agree well. (3) This is not true if the capillary-to-fiber ratio is 2. (4) In neither case, a Hill-type model furnishes a good description of the PO2 distributions. (5) Anisotropic diffusion may become important under critical O2 supply conditions. For a capillary-to-fiber ratio of 1, a Krogh-type model in which the O2 fluxes within the carrier-free layer are adapted according to Hellums (Microvasc. Res. 13: 131, 1977) yields almost identical PO2 distributions as the present 3-dimensional model.

Animals↗

Calculated intra- and extracellular PO2 gradients in heavily working red muscle.

A recently introduced three-dimensional analytical model of O2 diffusion to heavily working muscle that considers myoglobin-facilitated O2 diffusion inside the muscle fiber and a carrier-free layer separating erythrocytes and fiber is able to furnish the following new insights in O2 supply to red muscle at high performance. 1) Fiber PO2 profiles are essentially flat, and the major PO2 gradients are located in the perierythrocytic region, in good agreement with experimental findings [T. E. J. Gayeski and C. R. Honig, Am. J. Physiol. 251 (Heart Circ. Physiol. 20): H789-H799, 1986]. No specialized anatomical pericapillary barrier structure is required to explain these results. 2) A functional barrier to O2 diffusion has been identified that consists of the carrier-free layer and of the pericapillary muscle fiber portions. There are three reasons that make these structures act as a diffusion barrier: a "geometric reason," a "diffusivity-related reason," and a "myoglobin-related reason." 3) PO2 fields of adjacent red blood cells (RBCs) practically do not interact. 4) Small scale heterogeneities in capillary and RBC spacing are compensated for by high myoglobin-facilitated fiber diffusivity. Limiting factor for diffusional O2 transport is the number of RBCs present on the fiber surface.

Animals↗

Effects of red cell spacing and red cell movement upon oxygen release under conditions of maximally working skeletal muscle.

RBC spacing in capillaries plays an important role in that it determines the total number of RBCs contained in a capillary and, therefore, the total O2 flux out of the capillary. The detrimental effects of increased RBC spacing upon capillary O2 release are in part compensated for by enhanced O2 release out of single RBCs due to improved diffusion geometry and RBC movement. Non-uniformity of O2 flux brought about by the particulate nature of blood is considerably smaller than calculations which do not consider RBC movement indicate. It creates oscillations in the O2 supply to the tissue, the periodicity of which is fast, however, compared to the time constant of the PO2 decay in a temporarily unsupplied tissue. We conclude that non-uniformity of O2 flux out of capillaries due to large inter-erythrocytic plasma gaps does not play an important role for tissue O2 supply as long as average RBC spacing is sufficiently small to guarantee an appropriate overall capillary O2 flux.

Animals↗

[Chlorinated hydrocarbons in breast milk].

Chlorocarbons, which are used for cleaning purposes in both the home and industry, are of growing interest with respect to environmental pollution. We have therefore, compared the concentrations of chloroform (CH CL3), carbon tetrachloride (C CL4) and tetrachloroethylene (C2 CL4), determined by gas chromatography, in breast milk from 13 puerperal mothers from Innsbruck and the surrounding Tyrol with the respective data in 20 mothers from Linz and the surrounding industrial area. In fact, no elevation in chlorocarbon levels was detected in either group.

Austria↗

Theoretical analysis of oxygen supply to contracted skeletal muscle.

Honig and collaborators reported striking contradictions in current understanding of O2 supply to working skeletal muscle. Therefore we re-examined the problem by means of a new composite computer simulation. As inclusion of erythrocytic O2 desaturation and oxygen transport and consumption inside the muscle cell into a single model would entail immense numerical difficulties, we broke up the whole process into its several components: O2 desaturation of erythrocytes O2 transport and consumption in muscle fiber capillary transit time characterizing the period of contact between red cell and muscle fiber. "Erythrocyte model" as well as "muscle fiber model" both consist of a central core cylinder surrounded by a concentric diffusion layer representing the extracellular resistance to O2 diffusion (Fig. 1). Resistance layers in both models are to be conceived of as one and the same anatomical structure--even though in each model their shape is adapted to the respective geometry. By means of this overlap region a spatial connexion between both is given, whereas temporal coherence governing O2 fluxes and red cell spacing is derived from capillary transit time. Analysis of individual components is outlined as follows: Assuming axial symmetry of the problem a numerical algorithm was employed to solve the parabolic system of partial differential equations describing red cell O2 desaturation. Hb-O2 reaction kinetics, free and facilitated O2 diffusion in axial and radial directions, and red cell movement in capillary were considered. Resulting time courses of desaturation, which are considerably faster than the ones computed by Honig et al., are given in the following table (see also Fig. 3). (Formula: see text) Furthermore, we studied the respective importance of the several processes included in our model: Omission of longitudinal diffusion increased desaturation time by 15% to 23%, whereas effects of reaction kinetics and axial movement were 5% and 2% respectively. For time courses see Fig. 2. Nature and magnitude of extra-erythrocytic resistance to O2 diffusion playing a prominent part in O2 desaturation are scarcely explored. Calculated desaturation times based upon our new estimates (line 3 of above table) correspond well, however, with findings by Sinha, who observed 1.75 to 4-fold prolongation in omental and mesenteric capillaries compared to desaturation through equivalent plasma layers. The 3-dimensional elliptic system of partial differential equations describing stationary O2 transport through resistance layer and subsequent free and facilitated O2 diffusion and O2 consumption in muscle fiber was solved analytically.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

Heterogeneous oxygenation of rectal carcinomas in humans: a critical parameter for preoperative irradiation?

Tissue oxygenation was measured in 10 patients with differentiated adenocarcinoma in a very localized region in the middle part of the rectum (grade I - II, clinical stage II) by means of a cryophotometric micromethod. The results obtained clearly show that the oxygenation of differentiated rectal adenocarcinoma is distinctly lower than that of the normal rectal mucosa; tissue hypoxia or even anoxia are a common feature in those tumors; There exist considerable inter- individual differences among tumors of the same clinical staging and histological grading; substantial intra- individual heterogeneities in the oxygenation are evident within the same tumor and even within neighbouring microareas of the tissue. These findings imply that the commonly used classifications do not allow any conclusions concerning the oxygenation status, and probably the radiosensitivity of a tumor, respectively.

Adenocarcinoma↗

Relationship between size and oxygenation status of malignant tumors.

Analyzing the oxygenation status of tumors by means of the oxyhemoglobin saturation of single red blood cells within microvessels, there is clear evidence that tissue hypoxia and anoxia are inherent features during advanced stages of malignant growth. This is a consequence of distinct deteriorations of the convective and diffusive O2 transport with increasing tumor size leading to an O2 depletion in peripheral tissue layers around nutritive blood vessels. These alterations are combined with inhomogeneities of the oxygen distribution, both spatial and temporal. With enlarging tumor mass, the heterogeneities of the O2 supply distinctly intensify. Although in vitro experiments utilizing multicell spheroids failed to show very low oxygen tensions in necrotic regions, it is still proposed that chronic oxygen depletion is a paramount factor for the induction of necrosis in solid tumors under "physiological" in situ conditions.

Animals↗

Recommendations for using the standardized terminology of respiratory physiology in radiation research.

A succinct review of the terminology and of correlations between basic quantities in respiration physiology is given with special regard to oxygen as the gas of topical interest in radiation research and tumor pathophysiology. The role of the oxygen partial pressure gradient as the driving force of O2 diffusion is emphasized. It is generally recommended that the O2 partial pressure be considered when investigating oxygen diffusion and distribution problems. During those studies the physical boundary conditions, in particular the temperature, the barometric pressure, and the water vapor saturation, have to be considered and should be indicated. During equilibration of suspensions containing oxygen-consuming sites the impact of geometry and fluid agitation on the efficiency of gas exchange has to be taken into account. Reviews on solutions of diffusion equations, on numerical data for relevant constants to be considered, and on terminology and units in respiration physiology are included.

Animals↗

Impact of localized microwave hyperthermia on the oxygenation status of malignant tumors.

Upon heating at 40 degrees C for 30 minutes, the oxygenation of the tumor tissue significantly improved as compared with control conditions at 35 degrees C. In contradistinction to this, the tumor oxygenation significantly decreased directly after 43 degrees C- hyperthermia. A further temperature rise to 45 degrees C caused the oxygenation to drastically drop due to an almost complete cessation of nutritive blood flow. The changes in tumor oxygenation during hyperthermia seem to be predominatly mediated through changes in tumor blood flow, which showed the same directional changes.

Animals↗