Chronic exposure of rats to high concentrations of SO2 gas causes pathologic changes in airway similar to those seen in human chronic bronchitis. The purpose of this study was to examine the pulmonary mechanical correlates of these changes and to quantify the extent of mucous hypersecretion by measuring changes in mucous glycoproteins. Female Sprague-Dawley rats were exposed to 250 ppm SO2 gas, 5 h/d, 5 d/wk, for a period of 4 wk. Control rats were exposed to air only. On the day after the last SO2 exposure, rats were anesthetized, instrumented for the measurement of pulmonary resistance (RL) and dynamic compliance (Cdyn), and ventilated. Chronic SO2 exposure caused a small but significant increase in RL and decrease in Cdyn. Airway responsiveness to inhaled aerosolized methacholine was increased in SO2-exposed rats, as indicated by approximately 6.6- and 4.6-fold decreases respectively, in the doses of inhaled methacholine required to double RL or decrease Cdyn to 50% of baseline. SO2 exposure had no effect on the contractile response of the trachea measured in vitro. Tracheae and lungs from SO2-exposed animals exhibited 140 and 535% increases in measured neutral mucous glycoproteins, respectively, and 33 and 37% increases in acid glycoproteins. Our results indicate that this animal model of chronic bronchitis mimics the mucous hypersecretion, airway obstruction, and increased airway responsiveness observed in human bronchitis and may allow us to begin to probe their mechanistic basis.

To determine whether exposure to nitrogen dioxide (NO2) affects respiratory tract susceptibility to viral infection, CD-1 mice were inoculated intratracheally with murine cytomegalovirus (MCMV) during exposure to varying concentrations of NO2. Exposure lasted for 6 h per day; it began 2 consecutive days prior to instillation of MCMV and continued for 4 days after virus inoculation. Exposure to 5 ppm NO2 resulted in MCMV proliferation and a mild bronchopneumonia in some animals inoculated with 10(2) plaque-forming units of virus. Importantly, this inoculum was too low to produce either viral replication or histologic abnormalities in the lungs of air-exposed animals. We also found that the amount of virus required to infect animals exposed to 5 ppm of NO2 was 100-fold lower than that needed to consistently produce infection in air-exposed animals. Animals exposed to 5 ppm NO2 also exhibited depressed phagocytosis of colloidal Au198 in vivo as well as diminished macrophage destruction of instilled MCMV compared to air-exposed animals. These results demonstrate that exposure to 5 ppm NO2, although not associated with evidence of overt lung injury per se, is nevertheless capable of predisposing the lower respiratory tract to viral infection.

The purpose of this study was to evaluate the role of C fibers in airway responsiveness after exposure to ozone (O3) in rats. The role of C fibers in the decreases in heart rate (HR) and core body temperature (Tc) that occur after inhalation of O3 was also examined. Neonatal rats were treated with capsaicin (Cap) or the vehicle used to dissolve capsaicin (Veh). Cap has been shown to cause permanent destruction of C fibers. When they reached adulthood, conscious minimally restrained rats were exposed to 2 ppm O3 or to air for 3 h. Two hours after the cessation of exposure, rats were anesthetized and instrumented for the measurement of pulmonary mechanics and airway responsiveness to inhaled aerosolized methacholine. O3 had no effect on baseline pulmonary conductance (GL) in either Veh or Cap rats but did cause a decrease in dynamic compliance (Cdyn) in Cap rats (P < 0.05). In Cap rats, O3 exposure caused a marked increase in airway responsiveness; the doses of inhaled aerosolized methacholine required to decrease GL and Cdyn by 50% were 6.5-fold and 9.8-fold lower in O3-compared with air-exposed rats (P < 0.005). In contrast, in Veh rats, O3 did not alter responsiveness. During O3 exposure, there was a profound, almost 50%, decrease in HR as measured with implanted electrodes. A decrease in Tc (measured with a rectal probe) of approximately 2.5 degrees C also occurred during O3 exposure. There was no significant effect of Cap pretreatment on the magnitude of these O3-induced changes in HR and Tc. Our results are consistent with the hypothesis that C fibers act to inhibit the development of hyperresponsiveness elicited by O3 inhalation but do not contribute to O3-induced changes in HR or Tc.

We assessed the retention and clearance of inhaled particles in six anatomic compartments of the respiratory tract. Hamsters were exposed for 45 min to 0.9-micron fluorescent latex particles either at rest (n = 9) or while running on a laddermill (n = 9). Oxygen consumption, which was used to estimate minute ventilation, was continuously monitored. Three animals from each group, rest and exercise, were killed at 10 min, 24 h, or 7 days after the exposure. Morphometric techniques were used to determine the number of particles retained in nose and oropharynx (NOSE), trachea and extrapulmonary airways, intrapulmonary conducting airways, respiratory bronchioles, alveolar ducts (AD), and alveoli (ALV). At 10 min, total particle retention increased linearly as a function of O2 consumption (slope = 1.4 +/- 0.3 x 10(6) particles.ml-1.g-1.h-1, P less than 0.015). Exercised hamsters retained 4.4 times more total particles in their NOSE than rested hamsters, but parenchymal retention (AD + ALV) was unaffected. After 7 days, 95% of the particles were cleared from the NOSE, 80% from the trachea and extrapulmonary airways, 44% from intrapulmonary conducting airways and respiratory bronchioles, and 16% from AD and ALV. There was evidence of particle redistribution from AD to ALV during the 1st day. We conclude that exercise enhances the deposition of 0.9-micron particles in the upper respiratory tract but not in the parenchyma. Subsequently, the deposited particles are cleared at varying rates depending on the lung compartment.

Knowledge of the local and regional doses of inhaled particulates is crucial for inhalation therapy and for understanding the progression of pulmonary disease. We studied the deposition pattern of radioactively tagged particles in rats with chronic bronchitis. Rats were exposed to sulfur dioxide (SO2; 236 +/- 14 ppm) for 5 h/d, 5 d/wk for 7 wk to produce chronic bronchitis (CB). Control rats were exposed to room air. The control animals gained 85% more weight over the 7-wk period than did the CB rats. Five control and five CB rats were then exposed for 30 min to an insoluble 99mTc-labeled aerosol. The animals were killed within 5 min after the exposure period. The lungs were excised, dried at total lung capacity (TLC), and sliced into 1 mm sections. The distribution of the radiolabeled particles retained in the lungs was determined in two ways. First, autoradiographs were made of the distribution of the radioactivity throughout a lung slice. Autoradiographs were quantified by image analysis to determine the amount of radioactivity (relative density of the film) associated with airway versus parenchyma (ratio of airway to parenchyma density). The lung slices were then dissected into pieces, the weight and radioactivity content of each piece was measured, and its evenness index (EI) was calculated. This type of analysis enables the homogeneity of particle deposition throughout the lungs to be assessed. If deposition were totally uniform, the average EI would be 1.0 with an SD = 0. The total amount of radioactivity retained in the lungs was similar in control and CB rats.(ABSTRACT TRUNCATED AT 250 WORDS)