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Biomedical subjects

James S Ultman

Publications and source records attributed to James S Ultman.

7 recordsLinked to original sources

Three-dimensional simulations of reactive gas uptake in single airway bifurcations.

The pattern of lung injury induced by the inhalation of ozone (O(3)) depends on the dose delivered to different tissues in the airways. This study examined the distribution of O(3) uptake in a single, symmetrically branched airway bifurcation. Reaction in the epithelial lining fluid was assumed to be so rapid that O(3) concentration was negligible along the entire surface of the bifurcation wall. Three-dimensional numerical solutions of the continuity, Navier-Stokes and convection-diffusion equations were obtained for steady inspiratory and expiratory flows at Reynolds numbers ranging from 100 to 500. The total rate of O(3) uptake was found to increase with increasing flow rate during both inspiration and expiration. Hot spots of O(3) flux appeared at the carina of the bifurcation for virtually all inspiratory and expiratory Reynolds numbers considered in the simulations. At the lowest expiratory Reynolds number, however, the location of the maximum flux was shifted to the outer wall of the daughter branch. For expiratory flow, additional hot spots of flux were found on the parent branch wall just downstream of the branching region. In all cases, O(3) uptake in the single bifurcation was larger than that in a straight tube of equal inlet radius and wall surface area. This study provides insight into the effect of flow conditions on O(3) uptake and dose distribution in individual bifurcations.

Air Pollutants↗

Kinetics of ozone reaction with uric acid, ascorbic acid, and glutathione at physiologically relevant conditions.

This study quantified the reaction kinetics of O3 with three low molecular weight antioxidants-uric acid (UA), ascorbic acid (AH2), and glutathione (GSH)-found in respiratory mucous. Using a semi-batch reactor in which a 500 ml/min flow of air containing 1-5 parts per million of O3 contacted 3 ml of well-stirred physiological saline solution containing 100-200 microM antioxidant, we found that: (1) mass transfer resistances in the gas and liquid phases were successfully eliminated by the reactor design; (2) the reaction of O3 with UA, AH2 and GSH had stoichiometries of 1:1, 1:1, and 1:2.5, respectively; (3) the reactivity between O3 and antioxidants was in the order UA approximately AH2>GSH. Simulating the measured amounts of O3 absorbed and antioxidant consumed with a mathematical model, reaction rate constants of O(3) with UA, AH2, and GSH were found to be 5.83 x 10(4) M(-1) s(-1), 5.5 x 10(4) M(-1) s(-1), and 57.5 M(-0.75) s(-1), respectively.

Antioxidants↗

An axisymmetric single-path model for gas transport in the conducting airways.

In conventional one-dimensional single-path models, radially averaged concentration is calculated as a function of time and longitudinal position in the lungs, and coupled convection and diffusion are accounted for with a dispersion coefficient. The axisymmetric single-path model developed in this paper is a two-dimensional model that incorporates convective-diffusion processes in a more fundamental manner by simultaneously solving the Navier-Stokes and continuity equations with the convection-diffusion equation. A single airway path was represented by a series of straight tube segments interconnected by leaky transition regions that provide for flow loss at the airway bifurcations. As a sample application, the model equations were solved by a finite element method to predict the unsteady state dispersion of an inhaled pulse of inert gas along an airway path having dimensions consistent with Weibel's symmetric airway geometry. Assuming steady, incompressible, and laminar flow, a finite element analysis was used to solve for the axisymmetric pressure, velocity and concentration fields. The dispersion calculated from these numerical solutions exhibited good qualitative agreement with the experimental values, but quantitatively was in error by 20%-30% due to the assumption of axial symmetry and the inability of the model to capture the complex recirculatory flows near bifurcations.

Biological Transport, Active↗

Uptake of ozone in human lungs and its relationship to local physiological response.

To investigate whether intersubject variations in the dose of inhaled ozone (O(3)) cause corresponding variations in the physiological response, 28 female and 32 male nonsmokers participated in a 1-h continuous inhalation of clean air or 0.25 ppm O(3) while exercising on a cycle ergometer at a constant ventilation rate of 30 L/min. The exposure protocols included continuous monitoring of respiratory flow rate and O(3) concentration from which O(3) uptake (OZU) and fractional uptake efficiency (UE) were computed. Pre-to-post changes in forced expired volume in 1 s (%DeltaFEV(1)), peripheral cross section for carbon dioxide diffusion (%Delta A(P)), and Fowler dead space volume (V(D)) were also measured for each exposure. Individual values of UE ranged from .70 to .98 among all the subjects, with significant differences (p<.05) existing between men and women. These intersubject differences were inversely correlated with breathing frequency and directly correlated with tidal volume. The mean +/- SD values of %Delta FEV(1), %Delta A(P), and %Delta V(D) were all significantly more negative in the O(3) exposure session (-13.31 +/- 13.40, -8.14 +/- 7.62, and -4.20 +/- 5.12, respectively) than in the air exposure session (-0.06 +/- 4.56, 0.22 +/- 10.82, and -0.70 +/- 6.88, respectively). Finally, our results showed that neither %DeltaFEV(1) nor %Delta V(D) was correlated OZU, whereas there was a significant relationship (rho = -0.325, p = .0257) between %Delta A(P) and OZU. We conclude that the overall uptake of O(3) is a weak predictor of intersubject variations in distal airspace response, but is not a predictor of intersubject variations in conducting airway responses.

Adult↗

Changes in the carbon dioxide expirogram in response to ozone exposure.

The objectives of this study were to quantify pulmonary responses to ozone (O3) exposure by parameters computed from the carbon dioxide expirogram and to compare these responses to decrements in forced expired spirometry. Anatomical dead space (VD) was determined from the pure dead space and transition regions of the expirogram. Four alternative parameters were computed from the alveolar plateau: slope (S), normalized slope (NS), peripheral cross-sectional area (AP) and well-mixed peripheral volume (VMP). Forty-seven healthy nonsmokers (25 men and 22 women) participated in two research sessions in which they exercised on a cycle ergometer for 1 h while orally inhaling either room air at a minute ventilation of 30.6 +/- 3.6 L or room air mixed with 0.252 +/- 0.029 ppm O3 at a minute ventilation of 29.9 +/- 3.7 L. Carbon dioxide expirograms were measured before exposure, 10 min after exposure and 70 min after exposure. Percent changes (mean +/- SD) in expirogram parameters were significant (P < or = 0.002) at both 10 and 70 min after O3 exposure: VD(-4.2 +/- 5.1, -3.3 +/- 6.9), S(16.4 +/- 17.9, +15.1 +/- 20.2), NS(17.5 +/- 15.4, +15.9 +/- 19.2), AP(-8.1 +/- 7.6, -7.7 +/- 9.8) and VMP(-15.4 +/- 13.0, -13.0 +/- 15.2). Percent decrements of forced expired volume in one second (FEV1) were also significant at both 10 min (-13.3 +/- 13.4) and 70 min (-11.1 +/- 9.2) following O3 exposure. Changes in the expirogram as well as decrements in FEV1 were not significant at either time point after air exposure. Thus, the CO2 expirogram is useful for characterizing the effect of O3 exposure on gas transport, and for supplementing forced expired spirometry that is frequently used to quantify lung mechanics.

Adolescent↗

Uptake distribution of ozone in human lungs: intersubject variability in physiologic response.

The primary hypothesis of this study was that intersubject variation in uptake of inhaled ozone causes corresponding variation in the resulting physiologic response. The second hypothesis was that differences in breathing pattern and lung anatomy induce differences in ozone uptake. Sixty healthy nonsmokers participated in three exposure protocols during which their minute ventilation was 30 L/min, corresponding to moderate exercise. For the intermittent bolus exposure to ozone (BO3*), we measured the penetration volume at which 50% of the bolus was taken up (VP50%). Before and after continuous clean air exposure (Ca) and continuous ozone exposure (CO3: 0.25 ppm ozone), we measured forced expiratory volume in 1 second (FEV1), calculated as the percent change after exposure relative to start of exposure [%FEV1]). We also measured the cross-sectional area of the peripheral lung (Ap) for carbon dioxide (CO2) diffusion, calculated as the percent change after exposure relative to start of exposure (%Ap). After the CO3 session, we also measured ozone uptake (as ozone uptake rate) and fractional ozone uptake efficiency. Uptake efficiency ranged from 0.70 to 0.98 among all subjects. It was inversely correlated with breathing frequency (P = 0.000) but was not correlated with conducting airways volume (P = 0.333). VP50% ranged from 67 to 135 mL among all subjects and was directly correlated with conducting airways volume (P = 0.000). These results indicate that overall ozone uptake was related to breathing frequency but not to airway size, whereas internal distribution of ozone shifted distally as airway size increased. Values of %FEV1 (mean +/- SD: -13.71 +/- 12.99) and %Ap (-7.80 +/- 9.34) were both significantly more negative (P = 0.000) in the CO3 session than in the Ca (control) session (-0.055 +/- 4.57 and 0.40 +/- 11.03, respectively). Ozone uptake rate correlated with individual %Ap (P = 0.008) but not with individual %FEV1 (P = 0.575). Nor were individual %Ap or %FEV1 correlated with VP50%. Therefore, ozone uptake did not explain intersubject differences in forced expiratory responses in this study, but it did partially explain differences in the cross-sectional area available for gas diffusion in the peripheral lung.

Adult↗

Development of an assay for ozone-specific antioxidant capacity.

A method of determining the ozone-specific antioxidant capacity (OZAC) of lavage samples from the respiratory system was developed: Gaseous ozone (O(3)) was produced in cuvettes by irradiation with an ultraviolet lamp; aliquots of sample or of a saline control were then added and sufficient time was allowed for ozonation to reach completion; and an aliquot of indigo trisulfonate (ITS) was added to react with excess O(3). Because each molecule of O(3) rapidly bleaches one molecule of the deeply colored ITS, an OZAC value in concentration units was computed from the difference in light absorbance between the sample and the saline control multiplied by the extinction coefficient of ITS. Experiments in 0-40 micro M antioxidant solutions indicated that the OZAC values of uric acid and ascorbic acid were close to their actual concentrations and were independent of O(3) concentration. On the other hand, the OZAC of reduced glutathione and possibly human nasal lavage were nonlinearly related to antioxidant concentration and were directly related to O(3) concentration.

Antioxidants↗