Biomedical subjects

J S Ultman

Publications and source records attributed to J S Ultman.

At least 19 recordsLinked to original sources

PubMed2001

Longitudinal distribution of ozone and chlorine in the human respiratory tract: simulation of nasal and oral breathing with the single-path diffusion model.

In the single-path model of the respiratory system, gas transport occurs within a conduit of progressively increasing cross-sectional and surface areas by a combination of flow, longitudinal dispersion, and lateral absorption. The purpose of this study was to use bolus inhalation data previously obtained for chlorine (Cl(2)) and for ozone (O(3)) to test the predictive capability of the single-path model and to adjust input parameters for applying the model to other exposure conditions. The data, consisting of uptake fraction as a function of bolus penetration volume, were recorded on 10 healthy nonsmokers breathing orally as well as nasally at alternative air flows of 150, 250, and 1000 ml/s. By employing published data for airway anatomy, gas-phase dispersion coefficients, and gas-phase mass transfer coefficients while neglecting diffusion limitations in the mucus phase, the single-path model was capable of predicting the uptake distribution for O(3) but not the steeper distribution that was observed for Cl(2). To simultaneously explain the data for these two gases, it was necessary to increase gas-phase mass transfer coefficients and to include a finite diffusion resistance of O(3) within the mucous layer. The O(3) reaction rate constants that accounted for this diffusion resistance, 2 x 10(6) s(-1) in the mouth and 8 x 10(6) s(-1) in the nose and lower airways, were much greater than previously reported reactivities of individual substrates found in mucus.

Administration, Inhalation↗

PubMed2001

A hybrid computational fluid dynamics and physiologically based pharmacokinetic model for comparison of predicted tissue concentrations of acrylic acid and other vapors in the rat and human nasal cavities following inhalation exposure.

To assist in interspecies dosimetry comparisons for risk assessment of the nasal effects of organic acids, a hybrid computational fluid dynamics (CFD) and physiologically based pharmacokinetic (PBPK) dosimetry model was constructed to estimate the regional tissue dose of inhaled vapors in the rat and human nasal cavity. Application to a specific vapor would involve the incorporation of the chemical-specific reactivity, metabolism, partition coefficients, and diffusivity (in both air and tissue phases) of the vapor. This report describes the structure of the CFD-PBPK model and its application to a representative acidic vapor, acrylic acid, for interspecies tissue concentration comparisons to assist in risk assessment. By using the results from a series of short-term in vivo studies combined with computer modeling, regional nasal tissue dose estimates were developed and comparisons of tissue doses between species were conducted. To make these comparisons, the assumption was made that the susceptibilities of human and rat olfactory epithelium to the cytotoxic effects of organic acids were similar, based on similar histological structure and common mode of action considerations. Interspecies differences in response were therefore assumed to be driven primarily by differences in nasal tissue concentrations that result from regional differences in nasal air flow patterns relative to the species-specific distribution of olfactory epithelium in the nasal cavity. The results of simulations with the seven-compartment CFD-PBPK model suggested that the olfactory epithelium of the human nasal cavity would be exposed to tissue concentrations of acrylic acid similar to that of the rat nasal cavity when the exposure conditions are the same. Similar analysis of CFD data and CFD-PBPK model simulations with a simpler one-compartment model of the whole nasal cavities of rats and humans provides comparable results to averaging over the compartments of the seven-compartment model. These results indicate that the general structure of the hybrid CFD-PBPK model applied in this assessment would be useful for target tissue dosimetry and interspecies dose comparisons for a wide variety of vapors. Because of its flexibility, this CFD-PBPK model is envisioned to be a platform for the construction of case-specific inhalation dosimetry models to simulate in vivo exposures that do not involve significant histopathological damage to the nasal cavity.

Acrylates↗

PubMed2001

Ozone absorption in the human nose during unidirectional airflow.

This study addresses the effect of gas flow rate and ozone (O(3)) concentration on the uptake of this air pollutant in the nose. A nasal exposure system was developed in which a constant flow of humidified air (V) containing a constant concentration of O(3) (C(inlet)) entered one nostril and then exited the other nostril while a subject closed the velopharyngeal aperture. Experiments were conducted on 10 healthy nonsmokers for whom O(3) concentration was measured at the inlet nostril and the outlet nostril to determine the fraction of inhaled O(3) that was absorbed into the nasal mucosa (Lambda(nose)). Lambda(nose) decreased from 0.80 +/- 0.02 to 0.33 +/- 0.02 (SE) when V was increased from 3 to 15 l/min and C(inlet) was fixed at 0.4 ppm. Analysis of these data with a mathematical model indicated that O(3) uptake was limited by diffusion reaction through mucus, rather than by convective diffusion through the respired gas. A small decrease in Lambda(nose) from 0.36 +/- 0.02 to 0.32 +/- 0.01 was also observed when C(inlet) was increased from 0.1 to 0.4 ppm at a fixed V of 15 l/min. This may have been due to nonlinear reaction kinetics between O(3) and reactive substrates in mucus or an active response by a physiological process such as mucus secretion or transepithelial water influx.

Absorption↗

PubMed2000

Ozone uptake in the intact human respiratory tract: relationship between inhaled dose and actual dose.

Inhaled concentration (C), minute volume (MV), and exposure duration (T) are factors that may affect the uptake of ozone (O(3)) within the respiratory tract. Ten healthy adult nonsmokers participated in four sessions, inhaling 0.2 or 0.4 ppm O(3) through an oral mask while exercising continuously to elicit a MV of 20 l/min for 60 min or 40 l/min for 30 min. In each session, fractional absorption (FA) was determined on a breath-by-breath basis as the ratio of O(3) uptake to the inhaled O(3) dose. The mean +/- SD value of FA for all breaths was 0.86 +/- 0.06. Although C, MV, and T all had statistically significant effects on FA (P < 0.0001, P = 0.004, and P = 0.026, respectively), the magnitudes of these effects were small compared with intersubject variability. For an average subject, a 0. 05 change in FA would require that C change by 1.3 ppm, MV change by 46 l/min, or T change by 1.7 h. It is concluded that inhaled dose is a reasonable surrogate for the actual dose delivered to a particular subject during O(3) exposures of <2 h, but it is not a reasonable surrogate when comparisons are made between individuals.

Absorption↗

PubMed1999

Longitudinal distribution of chlorine absorption in human airways: comparison of nasal and oral quiet breathing.

The fraction of an inspired chlorine (Cl2) bolus absorbed during a single breath (Lambda) was measured as a function of bolus penetration (VP) into the respiratory system of five male and five female nonsmokers during both nasal and oral breathing at a quiet respiratory flow of 250 ml/s. The correspondence between VP and specific anatomic landmarks was found for each subject by a combination of acoustic reflection and nitrogen washout measurements. For both nasal and oral breathing, Lambda reached approximately 0. 95 at the distal end of the upper airways and reached 1.00 within the lower conducting airways. The values of a regional mass transfer parameter computed from the Lambda-VP data indicated that the resistance to Cl2 diffusion in the airway mucosa was negligible compared with the diffusion resistance in the respired gas. Changing the peak inhaled Cl2 concentration from 0.5 to 3.0 parts/million did not significantly affect the distribution of Cl2 absorption, suggesting that the underlying mass transport and chemical reaction processes were linear with respect to Cl2 concentration.

Adolescent↗

PubMed1999

Longitudinal distribution of chlorine absorption in human airways: a comparison to ozone absorption.

The bolus inhalation method was used to measure the fraction of inhaled chlorine (Cl(2)) and ozone (O(3)) absorbed during a single breath as a function of longitudinal position in the respiratory system of 10 healthy nonsmokers during oral and nasal breathing at respired flows of 150, 250, and 1,000 ml/s. At all experimental conditions, <5% of inspired Cl(2) penetrated beyond the upper airways and none reached the respiratory air spaces. On the other hand, larger penetrations of O(3) beyond the upper airways occurred as flow increased and during nasal than during oral breathing. In the extreme case of oral breathing at 1,000 ml/s, 35% of inhaled O(3) penetrated beyond the upper airways and approximately 10% reached the respiratory air spaces. Mass transfer theory indicated that the diffusion resistance of the tissue phase was negligible for Cl(2) but important for O(3). The gas phase resistances were the same for Cl(2) and O(3) and were directly correlated with the volume of the nose and mouth during nasal and oral breathing, respectively.

Absorption↗

PubMed1998

A CFD-PBPK hybrid model for simulating gas and vapor uptake in the rat nose.

In laboratory studies of rodents, the inhalation of organic vapors often results in preferential damage to olfactory epithelium. Such focal lesion formation may be due either wholly or in part to a corresponding nonuniformity in the spatial distribution of vapor uptake within the nasal cavities. As a tool for determining this dose distribution, a mathematical model based on a combination of computational fluid dynamics (CFD) and physiologically based pharmacokinetic (PBPK) modeling was developed for simulating toxicant vapor uptake in the rat nose. The nasal airways were subdivided into four distinct meatuses selected such that each contained a major air flow stream. Each meatus was further divided into four serial regions attached to separate tissue stacks containing mucus, epithelial, and subepithelial compartments. Values for the gas-phase mass transfer coefficients and gas flows in the 16 airway regions were determined by a solution of the Navier-Stokes and convection-diffusion equations using commercially available CFD software. These values were then input to a PBPK simulation of toxicant transport through the 16 tissue stacks. The model was validated by using overall uptake data from rodent inhalation studies for three "unreactive" vapors that were either completely inert (i.e., acetone), reversibly ionized in aqueous media (i.e., acrylic acid), or prevented from being metabolized by an enzyme inhibitor (i.e., isoamyl alcohol). A sensitivity analysis revealed that accurate values of the mass transfer coefficient were not necessary to simulate regional concentrations and uptake of unreactive vapors in the rat nose, but reliable estimates of diffusion coefficients in tissue were crucial for accurate simulations.

Air Pollutants↗

PubMed1998

Application of a hybrid computational fluid dynamics and physiologically based inhalation model for interspecies dosimetry extrapolation of acidic vapors in the upper airways.

This study provides a scientific basis for interspecies extrapolation of nasal olfactory irritants from rodents to humans. By using a series of short-term in vivo studies, in vitro studies with nasal explants, and computer modeling, regional nasal tissue dose estimates were made and comparisons of tissue doses between species were conducted. To make these comparisons, this study assumes that human and rodent olfactory epithelium have similar susceptibility to the cytotoxic effects of organic acids based on similar histological structure and common mode of action considerations. Interspecies differences in susceptibility to the toxic effects of acidic vapors are therefore assumed to be driven primarily by differences in nasal tissue concentrations that result from regional differences in nasal air flow patterns relative to the species-specific distribution of olfactory epithelium in the nasal cavity. The acute, subchronic, and in vitro studies have demonstrated that the nasal olfactory epithelium is the most sensitive tissue to the effects of inhalation exposure to organic acids and that the sustentacular cells are the most sensitive cell type of this epithelium. A hybrid computational fluid dynamics (CFD) and physiologically based pharmacokinetic (PBPK) dosimetry model was constructed to estimate the regional tissue dose of organic acids in the rodent and human nasal cavity. The CFD-PBPK model simulations indicate that the olfactory epithelium of the human nasal cavity is exposed to two- to threefold lower tissue concentrations of a representative inhaled organic acid vapor, acrylic acid, than the olfactory epithelium of the rodent nasal cavity when the exposure conditions are the same. The magnitude of this difference varies somewhat with the specific exposure scenario that is simulated. The increased olfactory tissue dose in rats relative to humans may be attributed to the large rodent olfactory surface area (greater than 50% of the nasal cavity) and its highly susceptible location (particularly, a projection of olfactory epithelium extending anteriorly in the dorsal meatus region). In contrast, human olfactory epithelium occupies a much smaller surface area (less than 5% of the nasal cavity), and it is in a much less accessible dorsal posterior location. In addition, CFD simulations indicate that human olfactory epithelium is poorly ventilated relative to rodent olfactory epithelium. These studies suggest that the human olfactory epithelium is protected from irritating acidic vapors significantly better than rat olfactory epithelium due to substantive differences in nasal anatomy and nasal air flow. Furthermore, the general structure of the hybrid CFD-PBPK model used for this study appears to be useful for target tissue dosimetry and interspecies dose comparisons for a wide range of inhaled vapors.

Acrylates↗

PubMed1997

Improvement of a respiratory ozone analyzer.

The breath-to-breath measurement of total respiratory ozone (O3) uptake requires monitoring O3 concentration at the airway opening with an instrument that responds rapidly relative to the breathing frequency. Our original chemiluminescent analyzer, using 2-methyl-2-butene as the reactant gas, had a 10% to 90% step-response time of 110 msec and a minimal detectable concentration of 0.018 parts per million (ppm) O3 (Ben-Jebria et al. 1990). This instrument was suitable for respiratory O3 monitoring during quiet breathing and light exercise. For this study, we constructed a more self-contained analyzer with a faster response time using ethylene as the reactant gas. When the analyzer was operated at a reaction chamber pressure of 350 torr, an ethylene-to-sample flow ratio of 4:1, and a sampling flow of 0.6 liters per minute (Lpm), it had a 10% to 90% step-response time of 70 msec and a minimal detectable concentration of 0.006 ppm. These specifications make respiratory O3 monitoring possible during moderate-to-heavy exercise. In addition, the nonlinear calibration and the carbon dioxide (CO2) interference exhibited by the original analyzer were eliminated. In breath-to-breath measurements in two healthy men, the fractional uptake of O3 during one minute of quiet breathing was comparable to the results obtained by using a slowly responding commercial analyzer with a quasi-steady material balance method (Wiester et al. 1996). In fact, fractional uptake was about 0.8 regardless of O3 exposure concentration (0.11 to 0.43 ppm) or ventilation rate (4 to 41 Lpm/m2).

Breath Tests↗

PubMed1996

Longitudinal distribution of ozone absorption in the lung: simulation with a single-path model.

A one-dimensional unsteady state diffusion model was used as a basis for simulating the absorption (lambda), breakthrough (V(B)), and dispersion (sigma2) of inhaled ozone boluses as a function of penetration (V(P)) into intact human lungs. The model idealized the respiratory system as a single equivalent tube with cross-sectional and surface areas that varied as a function of longitudinal position. Longitudinal gas transport in the lumen of the equivalent tube occurred by the joint action of bulk flow and a dispersion coefficient, D. Lateral absorption between respired gas and the tube wall was characterized by an overall mass transfer coefficient, K. By inputting published values of anatomic dimensions scaled to a 160-ml conducting airway volume, D values previously reported for inert insoluble gases, and K values equal to gas-phase transfer coefficients determined in physical lung models, a reasonable simulation of the lambda-V(P) distribution measured at a 250 ml/sec respiratory flow was obtained. Simulations of the corresponding V(B)-V(P) and sigma2-V(P) distributions both exhibited the correct shapes but underestimated the actual values. Although the addition of an estimated tissue resistance to K resulted in a poorer simulation of the data, an increase in conducting airway volume from a value of 160 ml estimated by the subjects' CO2 dead space to a value of 200 ml substantially improved the V(B)-V(P) and sigma2-V(P) simulations without sacrificing the quality of the lambda-V(P) simulation. We conclude that the inclusion of a tissue diffusion resistance is not necessary to properly simulate bolus inhalation data during quiet breathing, but a reliable measurement of conducting airway volume is crucial.

Absorption↗

PubMed1996

Longitudinal distribution of O3 absorption in the lung: gender differences and intersubject variability.

Because the National Ambient Air Quality Standard for ozone (O3) is intended to protect the most sensitive individuals in the general population, it is necessary to identify sources of intersubject variation in the exposure-dose-response cascade. We hypothesize that differences in lung anatomy can modulate exposure-dose relationships between individuals, and this results in differences between their responsiveness to O3 at a fixed exposure condition. During quiet breathing, the conducting airways remove the majority of inhaled O3, so the volume of this region should have an important impact on O3 dose distribution. Employing the bolus inhalation method, we measured the distribution of O3 absorption with respect to penetration volume (Vp), and using the Fowler single-breath N2 washout method, we determined the dead space volume (VD) in the lungs of 10 men and 10 women at a fixed respiratory flow of 250 ml/s. On average, the women absorbed O3 at smaller Vp than the men, and the women had smaller VD than the men. When expressed in terms of Vp/VD, the absorption distribution of the men and women was indistinguishable. Moreover, an interpretation of the O3 distribution in terms of an intrinsic mass transfer parameter (Ka) indicated that differences between the O3 dosimetry in all subjects, whether men or women, could be explained by a unique correlation with anatomic dead space: Ka (in s-1) = 610 VD-105 (in ml). Application of this result to measurements of O3 exposure response indicated that previously reported gender differences may be due to a failure in properly accounting for tissue surface within the conducting airways.

Absorption↗

PubMed1995

Acrolein-induced smooth muscle hyperresponsiveness and eicosanoid release in excised ferret tracheae.

Acrolein is a ubiquitous toxic air pollutant that can have adverse lung effects. To understand the mechanism governing airway reactivity in relation to acrolein uptake, in vitro experiments were conducted in which excised tracheae from ferrets were exposed for 1 hr to a unidirectional constant flow (100 ml/min) of an acrolein-in-air mixture at several concentrations (0-12.5 ppm). During exposure, acrolein uptake into the trachea was determined by a chromatographic analysis of gas samples taken at the entrance and at the exit of the trachea. Smooth muscle contractility in response to carbachol (CCh), acetylcholine (ACh), and potassium chloride (KCl) was measured following exposure, and eicosanoids released in the perfusate baths were assayed. The results indicate that the fractional uptake into an excised ferret trachea was strongly dependent on inlet concentration, implying that diffusion and reaction processes of acrolein in airway tissue are not linear. Only the low concentration of acrolein caused an increase of eicosanoid release from the exposed tracheae in the perfusate bath; it is possible that, at higher exposure concentration, the epithelium was sloughed off and most of the eicosanoids were lost. Although acrolein did not alter smooth muscle response to KCl, it did increase the contractile responses to CCh and ACh, suggesting an alteration in the pharmacomechanical but not the electromechanical coupling of ferret tracheal smooth muscle; therefore, it is more likely that this hyperresponsiveness occurs primarily by a mobilization of intracellular Ca2+ stores rather than by an increased influx of extracellular Ca2+ through voltage-dependent channels.

Acrolein↗

PubMed1994

Longitudinal distribution of ozone absorption in the lung: effects of respiratory flow.

In our previous work, we developed a bolus inhalation apparatus and measured the longitudinal distribution of ozone (O3) uptake in intact human lungs at a quiet respiratory flow of 250 ml/min. The objective of the present study was to determine the effect of alternative respiratory flows between 150 and 1,000 ml/s. Uptake was expressed as the O3 absorbed during a single breath relative to the amount of O3 in the inhaled bolus (lambda). Measurements of lambda were correlated with the penetration volume of the bolus into the respiratory tract (Vp). Vp in the range of 20-70 ml was considered to indicate upper airways (UA), the Vp interval of 70-180 ml was identified as lower conducting airways (CA), and Vp > 180 ml was associated with the respiratory air spaces (RA). During quiet oral breathing at 250 ml/s, lambda increased smoothly as Vp increased, with 50% of the inhaled O3 absorbed in the UAs and the remainder absorbed within the CAs such that no O3 reached the RAs. The effect of increasing the respiratory flow was to shift the lambda-Vp distribution distally such that significantly less O3 was absorbed in the UAs and CAs and some O3 reached the RAs. For example, at 1,000 ml/s, only 10% of the inhaled O3 was absorbed in UAs and 65% was absorbed in the CAs such that 25% reached the RAs.(ABSTRACT TRUNCATED AT 250 WORDS)

Absorption↗

PubMed1994

Longitudinal distribution of ozone absorption in the lung: comparison of nasal and oral quiet breathing.

Employing a bolus inhalation system, we noninvasively measured the fraction of inhaled ozone (O3) that is absorbed during a single breath (lambda) as a function of bolus penetration volume into the respiratory tract (Vp). During nasal breathing at a constant respiratory flow of 250 ml/s, lambda increased smoothly as Vp increased with 80% of the inhaled O3 absorbed in the upper airways and 90% absorbed at the distal end of the trachea. Oral breathing caused a distal shift of the lambda-Vp distribution to the extent that absorption in the upper airways was reduced to 50% and inhaled O3 was 90% absorbed only after a bolus reached the 13th bronchial generation. Therefore, an exercise-induced change from nasal to oral breathing can render the distal lung more susceptible to O3 damage because of an elevation in O3 dose. We also found that changing the peak inhaled bolus concentration over a 10-fold range of 0.4-4 ppm O3 did not affect the lambda-Vp distribution. This finding implies that the diffusion and chemical reaction dynamics that dictate O3 absorption are linear processes.

Absorption↗

PubMed1994

Human bronchial smooth muscle responsiveness after in vitro exposure to acrolein.

Human isolated bronchi obtained at thoracotomy from 42 patients were exposed to aqueous solutions of acrolein, and the resulting change in contractile responses was evaluated by measuring agonist cumulative concentration-response curves (CCRC). Contractile responses to carbachol were measured after a variety of exposure concentrations, from 0.01 to 3.0 microM, and at times from 5 to 60 min. The optimal condition to induce airway smooth muscle hyperresponsiveness was an exposure duration of 20 min at a concentration of 0.3 microM. The effect of acrolein exposure on human bronchial smooth muscle was also assessed by examining the contractile responses to potassium chloride (KCl), histamine, and neurokinin A (NKA) in both the absence and the presence of phosphoramidon. Although in vitro exposure of the human bronchus to 0.3 microM acrolein did not alter responses to KCl, it did increase the efficacy of carbachol and NKA without altering their potency. This concentration of acrolein also increased the contractile response to low concentrations of histamine and shifted the CCRC to the left. Pretreatment with phosphoramidon abolished the differential effect of acrolein on airway response to NKA. These results suggest that the mechanism of action of acrolein includes inactivation of airway neutral endopeptidase as well as alterations in the pharmacomechanical, but not the electromechanical, coupling of human bronchial smooth muscle.

Acrolein↗

PubMed1994

Noninvasive determination of respiratory ozone absorption: the bolus-response method.

Morphometric studies in animals exposed to ozone (O3), and mathematical simulations of O3 transport in human lungs indicate that O3 toxicity is focal in nature, causing tissue damage that is more pronounced in the proximal alveolar region (the proximal end of the respiratory airspaces in our compartment models) than in other airways. These findings suggest that the internal distribution of O3 uptake must be known in order to assess health risk reliably. In previous work (Ultman and Ben-Jebria 1990), we developed a fast-responding chemiluminescent O3 analyzer and a small-scale O3 generator, both of which are suitable for respiratory measurements. The objective of the current research was to integrate these instruments into a bolus inhalation system capable of noninvasively measuring the longitudinal distribution of O3 absorption in intact human lungs. With this system we aimed to carry out baseline experiments in healthy men during quiet oral breathing at a respiratory flow rate of 250 mL/sec, determine the effect of alternative respiratory flow rates between 150 and 1,000 mL/sec, compare the absorption distribution during quiet oral breathing with that during quiet nasal breathing, and ascertain the influence of a peak inspired concentration between 0.3 and 4.0 parts per million (ppm). Ozone uptake (lambda) was expressed as the amount of O3 absorbed during a single breath relative to the amount in the inhaled bolus. Measurements of lambda were correlated with the penetration volume (VP) of the bolus into the respiratory tract. Values of VP less than 70 mL were considered to be associated with the upper airways, values between 70 and 180 mL were associated with the lower conducting airways, and values greater than 180 mL were associated with the respiratory airspaces. During quiet oral breathing, lambda increased smoothly with VP, with 50% of the inhaled O3 absorbed in the upper airways and the balance absorbed within the lower conducting airways. This compares favorably with the results of direct-sampling methods, which have indicated that 40.4% of continuously inhaled O3 is removed by the extrathoracic airways (Gerrity et al. 1988). The effect of increasing the respiratory flow, which occurs when people exercise, was to shift the lambda-VP distribution distally so that significantly less O3 was absorbed in the upper airways and more reached the respiratory airspaces. Compared with oral breathing, nasal breathing caused a proximal shift in the lambda-VP distribution to the extent that absorption in the upper airways increased from 50% to 80%.(ABSTRACT TRUNCATED AT 400 WORDS)

Absorption↗

PubMed1993

Effect of in vitro exposure to acrolein on carbachol responses in rat trachealis muscle.

Isolated tracheal rings obtained from male Wistar rats 10 to 15 weeks old and weighing 300 to 400 g were exposed to aqueous solutions of acrolein, and the resulting change of smooth muscle contractility was evaluated by measuring the cumulative carbachol concentration-response curve. Using the product of acrolein concentration and time as a surrogate for the acrolein dose delivered to the smooth muscle cells, contractility measured after a variety of exposure concentrations from 0.01 to 3.0 microM and times from 5 to 60 min could be correlated in a dose-dependent manner. In the range of doses from 0.1 to 6 microM-min, relative contractility continuously increased from 0 to 50% above unexposed control values. At doses greater than 6 microM-min, the enhancement in contractility declined. This decline may have been due to cell damage or cell death which was so severe at a dose of 60 microM-min that contractility fell below control values. Below a threshold dose of 0.1 microM-min, acrolein had no effect on contractility. The role arachidonic acid metabolism in the enhancement of smooth muscle reactivity to carbachol was studied using indometacin to block the cyclo-oxygenase pathway and NDGA to block the lipoxygenase pathway. At a concentration of 10 microM of either indometacin or NDGA, the acrolein-induced enhancement in airway reactivity was completely inhibited. At lower concentrations, inhibition by these two chemicals was partially additive, suggesting that both the lipoxygenase and cyclo-oxygenase pathways play a role in the hyperreactive response.

Acrolein↗

PubMed1992

Simulation of ozone uptake distribution in the human airways by orthogonal collocation on finite elements.

Ozone transport in a rigid single-pathway anatomic model of the lung was analyzed by a stable convergent numerical algorithm, the method of orthogonal collocation on finite elements. The simulations predicted the dynamic behavior of gas phase concentration profiles for both ozone and an insoluble inert gas. An internal quasi-stationary diffusion front was observed during early inspiration for both gases. In addition, the absorptive distribution of ozone in lung airways was computed as a total dose as well as a tissue dose. The total dose of ozone decreased along the airway path from the mouth. However, the tissue dose of ozone increased along the conducting airways, reached a maximal dose in the terminal bronchioles, and decreased sharply in the respiratory airways.

Algorithms↗