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Biomedical subjects

J L Mauderly

Publications and source records attributed to J L Mauderly.

At least 91 records · Page 5Linked to original sources
PubMed1984

Diesel exhaust exposure system for animal studies.

Planned exposures of rodents to diesel exhaust required development of an exhaust generation and delivery system flexible enough to accommodate varied experimental designs. The features of the exposure system built to meet these needs are summarized. Essential aspects including both the exhaust dilution and delivery system and the computer monitoring and control functions are described. During the first 29 weeks of a study with target particle concentrations of 350, 3500, and 7000 micrograms/m3, the achieved values were 310, 3360, and 6830 micrograms/m3 with coefficients of variation of 23, 10, and 9%, respectively. The system has now operated reliably for more than 24 months.

Animals↗
PubMed1984

Respiratory function responses of animals and man to oxidant gases and to pulmonary emphysema.

Data on the respiratory functional responses of animals and humans to inhaled oxidant gases and to pulmonary emphysema were reviewed and compared. Comparisons included responses to short-term inhalation of ozone, nitrogen dioxide, and oxygen and the functional manifestations of chronic emphysema. The comparisons illustrated that animals and humans have qualitatively similar functional responses to the irritant, bronchoconstrictive, and sensitizing effects of acutely inhaled ozone and nitrogen dioxide. Animals and humans responded similarly to the inflammatory and edematous effects of inhaled oxygen. Similar changes in maximal expiratory flow-volume curves, pressure-volume curves, lung volumes, and alveolar-capillary gas exchange occurred in animals and humans with emphysema. These results suggest that similar respiratory functional changes occur in both animals and humans when similar morphological changes result from lung injury. This observation lends confidence to the use of laboratory animals in studies to predict the effects of long-term exposure of humans to inhaled oxidant gases.

Aged↗
PubMed1984

Sulfur dioxide-induced chronic bronchitis in beagle dogs.

This study was done to produce a model of chronic bronchitis. Twelve beagle dogs were exposed to 500 ppm sulfur dioxide (SO2) for 2 h/d, 5 d/wk for 21 wk and 4 dogs were sham-exposed to filtered ambient air for the same period. Exposure effects were evaluated by periodically examining the dogs using chest radiographs, pulmonary function, tracheal mucous clearance; and the cellular and soluble components of bronchopulmonary lavage fluids. Dogs were serially sacrificed after 13 and 21 wk of exposure and after 6 and 14 wk of recovery. Clinical signs produced in the SO2-exposed dogs included mucoid nasal discharge, productive cough, moist rales on auscultation, tonsilitis, and conjunctivitis. Chest radiographs revealed mild peribronchiolar thickening. Histopathology, tracheal mucous clearance measurements, and lavage cytology were consistent with a diagnosis of chronic bronchitis. It is concluded that repeated exposure to 500 ppm SO2 for 21 wk produced chronic bronchitis in the beagle dog. Complete recovery occurred within 5 wk following cessation of SO2 exposure.

Animals↗
PubMed1984

Characterization of diesel exhaust in a chronic inhalation study.

We describe characterization of the exposure atmosphere in a life-span study of rats and mice exposed to chronic inhalation of diluted diesel exhaust. Diesel exhaust was generated by one of two General Motors 1980 Model, 5.7-liter V8 diesel engines connected to an eddy current dynamometer/flywheel system and operated on the Federal Test Procedure urban driving cycle. Animals were exposed 7 hours/day, 5 days/week to exhaust at particle concentrations of approximately 7000, 3500, and 350 micrograms/m3 or to clean air. Throughout the 24-month study, the mean particle mass concentration remained within 5% of the target values. Measured gas concentrations of CO, CO2, NO, NO2, and hydrocarbons were roughly proportional to the dilution ratio. A combination of a Lovelace Multijet cascade impactor followed by a parallel flow diffusion battery gave mass median diameters of 0.23 to 0.26 microns averaged over complete cycles and geometric standard deviations larger than 4. The aerosol concentration profile was associated with the operating cycle. The measured diesel particle size was similar to previously reported values of particles released to the atmosphere from the same model engine.

Animals↗
PubMed1984

Noninvasive detection of airway constriction in awake guinea pigs.

Tidal volume measured by the barometric method is very sensitive to increases in compression and expansion of alveolar gas, such as would be expected to occur during airway narrowing or closure. By comparing a barometric method tidal volume signal (VT') with a reference tidal volume (VT) obtained with a head-out pressure plethysmograph, a simple index related to gas compressibility effects was calculated (VT/VT'). Changes in this index were compared with decreases in dynamic compliance (Cdyn) during histamine aerosol challenge of 15 Charles River Hartley guinea pigs. Decreases in VT/VT' occurred during all aerosol challenges and were correlated with decreases in Cdyn (r = 0.84, P less than 0.001). Decreases in VT/VT' were most marked at Cdyn values of less than 50% of base line. At Cdyn of less than 15% of base line, VT' was 3.1-4.8 times the VT reference signal. No increase in total pulmonary resistance was noted, and Cdyn and VT/VT' returned to base line after histamine exposure was stopped. We conclude that gas compressibility effects become substantial during histamine-induced airway constriction in the guinea pig and that the VT/VT' ratio appears to provide a simple noninvasive method of detecting these changes.

Animals↗
PubMed1984

Metabolism and macromolecular covalent binding of [14C]-1-nitropyrene in isolated perfused and ventilated rat lungs.

1-Nitropyrene (1-NP) originating from such sources as diesel exhaust emissions and coal combustion fly ash has been detected in the environment. 1-NP, in addition to being both a bacterial and mammalian mutagen, is carcinogenic in rats. The purpose of this study was to quantitate 1-NP metabolism and macromolecular covalent binding in the isolated perfused rat lung. Rat lungs were perfused with 2, 5, or 24 microM [14C]-1-NP for 90 min. Tidal volume and dynamic lung compliance were monitored continually throughout the perfusion to document the ventilatory pattern and the decay of tissue elasticity. Perfusate was sampled periodically throughout the duration of the experiment and analyzed for 1-NP metabolites with high-performance liquid chromatography. In all experiments, both dynamic lung compliance and tidal volume declined in a nearly linear manner and were approximately 60% of the initial value at the end of 90 min of perfusion. At all concentrations of [14C]-1-NP tested, less than 5 to 6% of the total amount of [14C]-1-NP added was metabolized in lungs from control and phenobarbital (PB)-treated rats. Lungs from control and PB- and 3-methylcholanthrene (3-MC)-treated rats metabolized [14C]-1-NP to oxidized, reduced, and conjugated metabolites. The major metabolites were 3-, 6-, and 8-hydroxynitropyrene. Small quantities of 10-hydroxynitropyrene, aminopyrene, and acetylaminopyrene were also detected in perfusates (less than 10% of the total metabolites). Treatment of rats with PB resulted in a 60% increase in the total metabolism of [14C]-1-NP, whereas treatment of rats with 3-MC resulted in a 10-fold increase in the rate of metabolism of [14C]-1-NP when compared to controls. Conjugate hydrolysis studies indicated that the water-soluble metabolites from lungs of control and PB- and 3-MC-treated rats consisted of hydroxynitropyrene glucuronides and hydroxynitropyrene sulfate conjugates. Quantities of 14C covalently bound to lung macromolecules after 90 min of perfusion from lungs of control and PB-treated rats were 0.06 to 0.21 nmol equivalents/g lung. However, in lungs from 3-MC-treated rats, there was a 20-fold increase in quantities of 14C covalently bound when compared to lungs from either control or PB-treated rats. The results from these studies point to the potential importance of lung metabolism in contributing to the metabolic fate of inhaled 1-NP.

Animals↗
PubMed1984

A comparison of starvation and elastase models of emphysema in the rat.

Starvation and elastase-induced changes in rat lung structure, biochemistry, and function were compared as models of human pulmonary emphysema. Ten-week-old male rats were instilled intratracheally with either porcine pancreatic elastase in saline (E) or with saline alone. A group of the saline-instilled rats were fed one third of their normal food intake until a 45% loss of body weight occurred (S). The remaining saline-instilled rats served as control animals (C). Post-treatment evaluations included in vivo respiratory function, lung histopathologic and morphometric analyses, lung tissue proteinolytic activity, and lung collagen. The E rats had in vivo respiratory function changes more similar to human emphysema than those of S rats. All lung volume subdivisions were decreased in S rats and increased in E rats. The volume-pressure curve of S rats was shifted to the right of the C curve, whereas that of E rats was shifted to the left. Forced expiratory flow rates of E rats were decreased at all lung volumes, but those of S rats were not. Both E and S rats had larger terminal air spaces and less alveolar surface area than did C rats. The S rats had more collagen per gram lung and higher proteinolytic activity than did C or E rats. These results show that, although starvation induces some changes characteristic of human emphysema, elastase-treatment provides a model more similar to the human disease.

Animals↗
PubMed1983

Radiation-induced pulmonary fibrosis resolves spontaneously if dense scars are not formed.

The relation of static compliance of excised lungs to collagen accumulation and histologic fibrosis was examined in Syrian hamsters inhaling sufficient 238PuO2 particles to achieve initial lung burdens of 50 or 100 nCi. Control animals were exposed to nonradioactive aerosols. Irradiated lungs from hamsters at both dose levels had compliance reduced to the same extent at point of maximal reduction. However, collagen accumulation was more closely related to 238Pu exposure level than the compliance measurements. Histologic examination revealed both diffuse alveolar thickening and some dense fibrous scars, the former predominating at lower dose levels. Hamsters exposed to 50 nCi 238PuO2 showed normal collagen content and static lung compliance with minimal histologic fibrosis 288 days after exposure. In contrast, hamsters exposed to 100 nCi had significant pulmonary fibrosis at that time and the highest incidence of dense scars at any time period. Such findings are consistent with a stiffening of lung parenchyma. They suggest that the diffuse interstitial fibrosis developed by this injury resolves spontaneously; dense fibrous scars, however, do not.

Animals↗
PubMed1982

Lung function and morphology of dogs after sublethal exposure to nitrogen dioxide.

The relationship between respiratory function and morphological changes in 10 dogs exposed for 6 h to 69 ppm nitrogen dioxide was studied. Two additional dogs served as controls. Functional assessments included breathing pattern, breathing mechanics, forced expiration, gas exchange, and acid-base status. Gross, microscopic, and ultrastructural evaluations were made of lung tissues from dogs killed at 0.1, 1.0, 2.0, 3.0, 7.0 and 14.0 d after exposure. Functional changes were similar to those reported for man. The principal dysfunction was gas-exchange impairment, apparently resulting from foam in the airways. Breathing-pattern alterations appeared to result from stimulation of neural receptors. Gas-exchange measurements provided the most useful indicators of the pulmonary damage observed in this study.

Animals↗
PubMed1982

Effect of elastase or histamine on single-breath N2 washouts in the rat.

A method for performing single-breath N2 washouts (SBNW) in rats was developed and the test's usefulness was studied using two experimentally induced models of lung disease. Rats were anesthetized, intubated with oral tracheal and esophageal catheters, and tested by plethysmography. The SBNW expirogram was recorded during exhalation after inhaling 100% O2 from residual volume. The slope of phase III (slope III), closing volume (CV), and closing capacity (CC) were calculated. Changes in the SBNW expirogram were compared with changes in breathing pattern, dynamic and quasistatic lung mechanics, lung volumes, and forced expiratory indices. Pre- and postinstillation tests were performed on rats treated with elastase or histamine and on untreated controls. The SBNW indices were altered at significant levels equal to those of other indices of lung function, and different patterns of change were induced by the two disease models. Elastase increased CV and CC, but slope III was unchanged. Other tests suggested loss of elastic recoil and expiratory flow limitation. Histamine increased slope III, but CV and CC were unchanged. Other tests suggested large airway constriction. These results suggested the usefulness of the SBNW in rats, but the relationships between SBNW changes and underlying physiological phenomena remain to be defined.

Animals↗
PubMed1982

The effects of emphysema on oxygen toxicity in rats.

In order to determine if lungs with emphysema respond to oxygen toxicity in a different way from normal lungs, the effects of hyperoxia on pulmonary function, morphologic aspects, and survival were studied in rats with enzyme-induced emphysema. A hyperoxic pulmonary syndrome similar to adult respiratory distress syndrome (ARDS) was produced by a continuous 48-h exposure to 100% oxygen at 1 atm. An emphysematous condition was induced by intratracheal instillation of porcine pancreatic elastase. The 4 study groups consisted of (1) control, (2) oxygen-treated, (3) elastase-treated, and (4) combined oxygen-elastase-treated rats. The emphysematous rats exposed to 100% O2 had reductions in quasi-static compliance and CO diffusing capacity similar to those in oxygen-treated normal animals. They also had reductions in forced expiratory volumes and flow rates similar to those in rats treated with elastase alone. Histologically, there was no enhancement or attenuation of emphysematous or ARDS lesions in the combined oxygen-elastase lungs compared with that in lungs treated with only one agent. Emphysematous and normal rats were also exposed for 96 h to a similar hyperoxic atmosphere to evaluate survival. The survival curves for these 2 groups were not statistically different. These results indicate that the severity of ARDS alterations was not affected by the emphysematous condition, and hyperoxia did not enhance or attentuate preexisting emphysematous lesions. These findings suggest that emphysematous lungs respond to hyperoxia in a similar fashion to normal lungs, and that the functional and structural manifestations of oxygen toxicity are simply superimposed over preexisting emphysematous changes.

Animals↗
PubMed1982

Inhalation toxicology of diesel exhaust particles.

Our present knowledge of the health effects of diesel exhaust particles can be summarized as follows: 1. Diesel exhaust particles are very small in size and consist of a carbonaceous core with a myriad of adsorbed hydrocarbon compounds that are readily extracted with organic solvents. 2. The particle extracts are cytotoxic and mutagenic in in vitro bacterial and mammalian cell cultures. 3. The particle extracts area carcinogenic when painted on mouse skin along with a suitable promoter. 4. Inhaled particles readily deposit in the respiratory tract, a portion is rapidly cleared and a substantial portion is retained for long periods of time (over 100 days) in the lung. 5. Adsorbed hydrocarbon compounds slowly dissociate from the particles in biological media and presumably in the lung. 6. Detoxification mechanisms act on the hydrocarbon compounds released from the particles to minimize effects in in vitro systems and presumably in vivo.

Air Pollutants↗
PubMed1979

Ventilation, lung volumes and lung mechanics of young adult and old Syrian hamsters.

The breathing pattern, subdivisions of lung volume and quasistatic pressure-volume relationships of 15 and 65 week old hamsters (Mesocricetus auratus) anesthetized with halothane were measured by plethysmography. Body weights, tidal volumes and minute volumes of the younger and older groups were nearly identical. All lung volumes were larger in the older hamsters but there were no significant age-related differences in the relative proportions of lung volume subdivisions. Quasistatic lung compliance was greater in the older group but differences in pressure-volume relationships were not significant when volume was expressed as percent of total lung capacity. It appears that hamster lungs undergo significant volume changes with age during adulthood, but the pattern of change is different from that observed in man and dogs.

Age Factors↗
PubMed1979

Toxicity of 0.4- and 0.8-microm sulfuric acid aerosols in the guinea pig.

To determine mortality caused by inhaled sulfuric acid mist, groups of Hartley guinea pigs 2-3 mo old were exposed for 8 h to graded concentrations of aerosols of 0.4 or 0.8 microm mass median aerodynamic diameter. Relative humidity during exposures was maintained at 70-80%. Based on probit analysis, the concentration required to produce 50% mortality (LC50) for deaths to 21 d after exposure was 30 mg/m3 for the 0.8-microm aerosol. For the 0.4-microm aerosol, the LC50 was above 109 mg/m3, the highest concentration obtainable at that particle size. At both particle sizes, the animals either tended to develop severe dyspnea and die minutes (0.4 microm) or hours (0.8 microm) thereafter or appeared nearly unaffected. Lesions in animals that died as a results of 0.4-microm exposures were restricted to hyperinflation; animals that died as a result of 0.8-microm exposures also showed hemorrhage and transudation. No gross or histopathologic changes were observed in animals that appeared unaffected during exposure. Differences in total and/or regional respiratory tract deposition may account for the different responses to the two aerosols.

Aerosols↗