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Biomedical subjects

P W Scherer

Publications and source records attributed to P W Scherer.

At least 19 recordsLinked to original sources

Modelling steady state pulmonary elimination of He, SF6 and CO2: effect of morphometry.

We studied the influence of acinar morphometry on the shape of simulated expirograms computed from a single path convection-diffusion model that includes a source term for gas evolution from the blood (Scherer et al., J. Appl. Physiol. 64: 1022-1029, 1988). Acinar structure was obtained from published data of 3 different lung morphometries. The simulations were performed over a range of tidal volumes (VT) and breathing frequencies (f) comparable to those observed in a previously reported human study. Airways dead space (VDaw) increased with VT in all the morphometric models tested and in the experimental data. The increase in VDaw with VT was inversely related to the diffusivity of the evolving gas and to the rate of increase in airway cross-section of the most mouthward (proximal) alveolated generations of the models. Normalized phase III slope for all the gases decreased with increasing VT in all the models as was previously reported for healthy human subjects. In the model simulations, the greatest sensitivity of phase III slope to VT was seen with the least diffusible gas using the airway morphometry with the smallest cross-sectional areas in the proximal alveolated generations. We conclude that both VDaw and phase III slope of an evolving gas are sensitive to the geometry of the proximal acinar airways and that this is manifest by their dependence on tidal volume, breathing frequency, molecular diffusivity and alveolar/blood source emission rate. The model simulations indicate that heterogeneity of gas washout is not required to explain the magnitude of the phase III slope in healthy human subjects.

Carbon Dioxide

Sensitivity of CO2 washout to changes in acinar structure in a single-path model of lung airways.

A numerical solution of the convection-diffusion equation with an alveolar source term in a single-path model (SPM) of the lung airways simulates steady state CO2 washout. The SPM is used to examine the effects of independent changes in physiologic and acinar structure parameters on the slope and height of Phase III of the single-breath CO2 washout curve. The parameters investigated include tidal volume, breathing frequency, total cardiac output, pulmonary arterial CO2 tension, functional residual capacity, pulmonary bloodflow distribution, alveolar volume, total acinar airway cross sectional area, and gas-phase molecular diffusivity. Reduced tidal volume causes significant steepening of Phase III, which agrees well with experimental data. Simulations with a fixed frequency and tidal volume show that changes in blood-flow distribution, model airway cross section, and gas diffusivity strongly affect the slope of Phase III while changes in cardiac output and in pulmonary arterial CO2 tension strongly affect the height of Phase III. The paper also discusses differing explanations for the slope of Phase III, including sequential emptying, stratified inhomogeneity, and the issue of asymmetry, in the context of the SPM.

Carbon Dioxide

Diffusivity, respiratory rate and tidal volume influence inert gas expirograms.

We modified, and developed software for, a computer-controlled quadrupole mass spectrometer to measure complete breath-by-breath expirograms of helium (He) and sulfur hexafluoride (SF6) exhaled during the infusion of saline saturated with the inert gases. He and SF6 have similar blood solubilities but very different gas phase diffusivities allowing examination of the influence of gas phase diffusivity on steady state inert gas expirograms. We studied six normal human volunteers in nine separate studies and examined the influence of tidal volume (VT) and breathing frequency (f) on the airways dead space (VDaw) and alveolar plateau slope (phase III) for the inert gases and CO2. The experimental data showed a reduction in VDaw with rapid shallow breathing, while phase III slope increased by a factor of two to three. We critically evaluated the data and methodology of these and previously reported studies of continuous and single breath washout of He and SF6. In general the 15 to 20 ml differences in VDaw between He and SF6 were in keeping with previous studies by others. The ratio of phase III slopes of SF6 to He reported by us previously (Scherer et al., J. Appl. Physiol. 64: 1022-1029, 1988) was 3.13. In the current study, which includes the analysis of more than 400 He and SF6 breaths, the ratio of SF6 to He slope was 1.85. The difference between the two studies was largely related to the improved methodology of the current study, particularly for the measurement of He. The results support the conclusion that diffusivity is an important component of both phase II and phase III of the expirogram. However, the difference in phase III between He and SF6 is somewhat less than previously reported.

Adult

Studies of wall shear and mass transfer in a large scale model of neonatal high-frequency jet ventilation.

The problem of endotracheal erosion associated with neonatal high-frequency jet ventilation (HFJV) is investigated through measurement of air velocity profiles in a scaled up model of the system. Fluid mechanical scaling principles are applied in order to construct a model within which velocity profiles are measured by hot-wire anemometry. The effects of two different jet geometries are investigated. Velocity gradients measured near the tracheal wall are used to measure the shear stresses caused by the jet flow on the wall. The Chilton-Colburn analogy between the transport of momentum and mass is applied to investigate tracheal drying caused by the high shear flow. Shear forces are seen to be more than two times higher for jets located near the endotracheal tube wall than for those located axisymmetrically in the center of the tube. Since water vapor fluxes are dependent on these shears, they are also higher for the asymmetric case. Fluxes are shown to be greatly dependent on the temperature and relative humidity of the inspired gas. Water from the tracheal surface may be depleted within one second if inspired gases are inadequately heated and humidified. It is recommended that the design of neonatal HFJV devices include delivery of heated (near body temperature), humidified (as close to 100% humidity as possible) gases through an axisymmetric jet to best avoid the problem of endotracheal erosion.

High-Frequency Jet Ventilation

A model of cigarette smoke particle deposition.

A computer model of aerosol deposition has been extended to cover particle sizes representative of cigarette mainstream and sidestream smoke particles. The model is the first to theoretically predict total airway depositions of mainstream particles in a range which agrees with experimentally determined literature values by including effects of hygroscopicity and normal smoking breathing patterns. The hygroscopic characteristics of cigarette smoke particles are modeled as if they were saturated sodium chloride droplets. A discussion is included showing that this assumption is consistent with presently available data on the hygroscopic characteristics of cigarette smoke. Detailed regional depositions are provided. Though most of the particles are shown to deposit in the periphery, the surface concentrations of deposited particles are not necessarily much greater there than in centrally located airways. A peak in surface concentration at the third generation is exhibited, despite low total depositions there. Central airway surface concentrations are shown to be relatively independent of breathing pattern and airway geometry, implying that the effects of cigarette smoke particle deposition cannot be greatly reduced by changing the pattern of smoke inhalation. For sidestream smoke particles, total percent depositions agree with literature values of 7%-20% for both nonhygroscopic and hygroscopic particles. Deposition is seen to be favored in the periphery of the lung, though surface concentrations of the deposited material can be greater in Weibel Generations 3-6. Peak surface concentrations are again seen to occur in Generation 3. The increased toxicity of sidestream smoke particles may make them as unhealthy as mainstream smoke particles, despite the higher depositions observed for mainstream smoke.

Computer Simulation

Convective mixing mechanisms in high frequency intermittent jet ventilation.

A liquid flow visualization technique was used to identify the location of neutrally buoyant bead clouds injected into airway models during flows simulating high frequency intermittent jet ventilation (HFIJV) in neonatal lungs. The motions of these bead clouds show that the convective or bulk mixing that occurs during HFIJV is made up of two parts; a turbulent convective exchange with the atmosphere caused by the jet in the trachea and a streaming motion along the airways driven by an interaction between the jet and the expansion and contraction of the airways due to their compliance. These convective streaming motions combine with molecular diffusion to produce augmented diffusion which transports O2 and CO2 between the trachea and the peripheral alveoli. Optimizing HFIJV (as well as other forms of HFV) depends on maximizing these airway convective streaming flows which depend on many more lung and fluid mechanical parameters than are necessary to describe conventional mechanical ventilation.

High-Frequency Jet Ventilation

The biophysics of nasal airflow.

The biophysics of nasal airflow involve the measurement, analysis, and understanding of bulk airflow or momentum transport through the nasal cavity and of the exchange of mass and heat laterally between the air stream and the walls. In both of these areas, optimal progress depends on judicious, combined, and continuous use of physical models, mathematical calculations, and measurements made on human subjects. The progress that has been made to date is both fascinating and encouraging and suggests that great improvement in understanding, diagnosis, and treatment of nasal and upper airway disease will be possible in the future through closer contact and cooperation between clinicians and physical and biological scientists.

Airway Resistance

Numerical and experimental study of steady-state CO2 and inert gas washout.

The predictions of a single-path trumpet-bell numerical model of steady-state CO2 and infused He and sulfur hexafluoride (SF6) washout were compared with experimental measurements on healthy human volunteers. The mathematical model used was a numerical solution of the classic airway convention-diffusion equation with the addition of a distributed source term at the alveolar end. In the human studies, a static sampling technique was used to measure the exhaled concentrations and phase III slopes of CO2, He, and SF6 during the intravenous infusion of saline saturated with a mixture of the two inert gases. We found good agreement between the experimentally determined normalized slopes (phase III slope divided by mixed expired concentration) and the numerically determined normalized slopes in the model with no free parameters other than the physiological ones of upper airway dead space, tidal volume, breathing frequency, and breathing pattern (sinusoidal). We conclude 1) that the single-path (Weibel) trumpet-bell anatomic model used in conjunction with the airway convection-diffusion equation with a distributed source term is adequate to describe the steady-state lung washout of CO2 and infused He and SF6 in normal lungs and 2) that the interfacial area separating the tidal volume fron from the functional residual capacity gas, through which gas diffusion into the moving tidal volume occurs, exerts a major effect on the normalized slopes of phase III.

Carbon Dioxide

Airway deposition of hygroscopic heterodispersed aerosols: results of a computer calculation.

A new computer model is developed and used to calculate the deposition of inhaled heterodispersed hygroscopic aerosols for mouth breathing in a Weibel symmetric bronchial tree. The model was first validated by obtaining good agreement with recent experimental and theoretical data on regional and total airway deposition of monodispersed and heterodispersed nonhygroscopic aerosols. The model was then used to obtain predictions of regional and total deposition of heterodispersed hygroscopic aerosol particles (droplets of NaCl solutions). Parameters that were varied in the hygroscopic calculations include initial droplet NaCl concentration, time of inspiration and expiration, volume of aerosol inspired, period of breath holding, and initial inhaled lognormal aerosol mass median diameter and geometric standard deviation. Results of the computer calculations show that increasing heterodispersity tends to flatten and broaden regional deposition curves when fraction of inhaled mass deposited is plotted vs. inhaled mass median aerodynamic particle diameter. Hygroscopicity is shown to increase tracheobronchial and pulmonary airway deposition with hypertonic NaCl solution aerosols showing increases over isotonic and nonhygroscopic aerosols of up to 200%.

Aerosols

Maximization of pulmonary hygroscopic aerosol deposition.

A newly developed computer model is used to predict the aqueous salt solution concentration, breathing pattern, and inhaled droplet size distribution parameters that will maximize pulmonary deposition of hygroscopic medicinal aerosols. The parameter values providing maximum pulmonary deposition include 1) a NaCl concentration in the aerosolized solution of 0.035 g/ml or higher if the subject can tolerate it, 2) as nearly a monodispersed inhaled aerosol size distribution as possible, 3) an aerosol mass median diameter of 2-3 micron, and 4) slow (7 breaths/min) uninterrupted breathing of 1.5-2 liters of aerosol/breath. With these values, the model predicts that pulmonary deposition can be increased by greater than 100% relative to the deposition achieved in conventional inhalation therapy with isotonic saline-based medications.

Aerosols

Measurement of local mass transfer coefficients in a cast model of the human upper respiratory tract.

Local mass transfer coefficients measured using the naphthalene sublimation technique in an acrylic cast model of the human upper respiratory tract are reported as the Sherwood numbers for the corresponding regions. A steady air flow rate of 12 L per min was used for all measurements. Values of the Sherwood number are seen to be highest in the nasal cavity and proximal nasopharynx while a minimum value occurs just downstream from the larynx. Local values of the Nusselt number obtained in the trachea and proximal nasal cavity assuming a complete heat and mass transfer analogy agree well with in-vivo physiological measurements. The mass transfer coefficients found can be incorporated into an analytical model of respiratory heat and water vapor transfer or into a model of pollutant gas uptake in the respiratory tract.

Acrylates

A theoretical model of localized heat and water vapor transport in the human respiratory tract.

A steady-state, one-dimensional theoretical model of human respiratory heat and water vapor transport is developed. Local mass transfer coefficients measured in a cast replica of the upper respiratory tract are incorporated into the model along with heat transfer coefficients determined from the Chilton-Colburn analogy and from data in the literature. The model agrees well with reported experimental measurements and predicts that the two most important parameters of the human air-conditioning process are: the blood temperature distribution along the airway walls, and the total cross-sectional area and perimeter of the nasal cavity. The model also shows that the larynx and pharynx can actually gain water over a respiratory cycle and are the regions of the respiratory tract most subject to drying. With slight modification, the model can be used to investigate respiratory heat and water vapor transport in high stress environments, pollutant gas uptake in the respiratory tract, and the connection between respiratory air-conditioning and the function of the mucociliary escalator.

Body Temperature Regulation

Regional control of local airway heat and water vapor losses.

The regulation of local heat and water vapor losses along the respiratory tract is examined based on a theoretical model of respiratory air conditioning and physiological data. The theoretical model is a quasi-steady one-dimensional model descriptive of the localized process of heat and water transport within the airways. During nasal breathing the model is most sensitive to the following two parameters: 1) the gradient of blood temperature along the airway wall and 2) the nasal air space volume. Thermoregulatory control of these two factors within the primary conditioning region, the upper airway, establishes the overall respiratory heat and water loss. Upper airway thermoregulation, however, also effects the heat and water demands placed on the secondary conditioning region, the tracheobronchial airways. Similar to the upper airway, the tracheobronchial airway wall temperature varies in response to changing demands. The bronchial circulation is shown to provide a major source of heat within the first several bronchial generations where the greatest heat and water fluxes within the lung are predicted to occur. Control of the bronchial blood flow may therefore directly influence the bronchoconstrictive response in asthmatics.

Body Temperature Regulation

Growth of hygroscopic aerosols in a model of bronchial airways.

Experiments have been performed on the "breathing" of micron-size hygroscopic aerosols in and out of a four-generation model of the bronchial tree. Comparison of the experimental results on aerosol growth in the model with the classical theory for dilute aqueous solutions of nonpolar salts shows a) that the theory is applicable to conditions in the airways, b) that to a high degree of approximation the process represents deposition followed by growth, and c) that there is a significant amount of trapping of particles near their equilibrium size in the deeper model tubes. These experiments are the first to verify that the classical particle growth theory is applicable to the particle sizes and environmental conditions present in the human airways during hygroscopic aerosol therapy. This theory will be useful in designing an optimal hygroscopic aerosol delivery system, but several questions including the method of generation and the effect of drug solutions on particle equilibriums remain to be answered.

Aerosols

Measurement of axial diffusivities in a model of the bronchial airways.

Values for the effective axial diffusivity D for laminar flow of a gas species in the bronchial airways have been obtained as a function of the mean axial gas velocity u by experiment measurements of benzene vapor dispersion in a five generation glass tube model of the bronchial tree. For both inspiration and expiration D is seen to be approximately a linear function of u over the range of Reynolds' numbers 30-2,000 corresponding to peak flows in bronchial generations 0-13 under resting breathing conditions. The diffusivity for expiration is seen to be approximately one-third that for inspiration due presumably to increased radial mixing at bifurcations during expiration. The effective diffusivities relative to the molecular diffusivity can be expressed by the formulas D/Dmol = 1 + 1.08 NPe for inspiration and D/Dmol = 1 + .37 N-Pe for expiration. These velocity dependent diffusivities help to explain the short transit times of gas boluses from mouth to alveoli and will aid in the analysis of airway gas mixing by mathematical transport equations.

Bronchi