Nitrogen dioxide exposure and development of pulmonary emphysema

Abstract

This study assessed the relationship between nitrogen dioxide inhalation and the development of pulmonary emphysema and investigated how the severity of preexisting emphysema brought about by protease (elastase) instillation into the lung may be augmented by a subchronic exposure to a relatively high concentration of nitrogen dioxide. Lungs of adult Fischer-344 rats were evaluated for emphysematous changes after (1) a single intratracheal instillation of elastase (E), (2) a 25-d exposure to 35 ppm nitrogen dioxide (NO2), and (3) elastase instillation followed by 25-d exposure to 35 ppm NO2 (E + NO2). Rats instilled with sterile normal saline and subsequently exposed to filtered air served as a control group (NS). Residual volumes (RV) of the NO2 and NS groups were virtually identical, whereas the RV of the E and E + NO2 lungs (2.3 and 2.3 ml, respectively) were significantly greater than those of the NS and NO2 lungs (1.3 and 1.4 ml, respectively). Directionally similar changes in the excised lung volumes and total lung capacities were obtained with the E and E + NO2 groups; NO2 alone, however, did not alter these volumetric parameters. No differences in arterial blood gases and pH values, minute ventilation, or breathing frequencies were found among the experimental groups. The mean linear intercept values (MLI) obtained with the NS and NO2 exposed lungs were essentially identical with average values of approximately 62 micron. This morphometric parameter was substantially increased in the E- and E + NO2-exposed lungs; no significant differences, however, were found between the MLI values obtained with the E and E + NO2 lungs (approximately 95 and approximately 97 micron, respectively). From these data, as well as histologic examinations of lung sections for evidence of emphysema, we conclude that (1) a subchronic, moderately high level of NO2 exposure does not produce an irreversible emphysematous lesion in the rat model and (2) exposure of rats to 35 ppm for 25 d after elastase instillation into the lungs does not potentiate protease-induced emphysema or bring about a progression in preexisting emphysema.

Nitric Acid-Induced Bronchiolitis in Rats Mimics Childhood Bronchiolitis obliterans

“…Nitrogen dioxide has been shown to induce BO and also emphysema in different animal species [17][18][19] . Recently, Svetlecic et al [20] developed a constricitive BO rat model (with similarities to posttransplantation BO) using papaverine, the alkaloid of the Sauropus plant.…”

Temporal Sequence of Early Alterations in Rat Lung Following Thoracic X-irradiation

“…1982) . Following injections of anaesthetic, and immediately prior to the onset of apnoea, rats from each group were exsanguinated via carotid artery transection, and the trachea and lungs of each animal were excised en bloc and weighed after removal of the heart, extrapulmonary mediastinal tissue, and oesophagus (Stavert et al 1986) . After the lung wet weight measurement, the bronchus leading to the right cranial lung lobe was tied off with fine suture, and the lobe was removed .…”

Overview of nitrogen dioxide effects on the lung with emphasis on military relevance

“…Airway hyperresponsiveness may be elicited in normal humans after exposure to 2.0 ppm x I h (Mohsenin, 1987a) and in asthmatic patients after exposure to as low as 0.5 ppm x 1 h (Mohsenin, 1987b). In cigarette smokers levels of 50-250 ppm of NO 2 have been reported (Norman and Keith, 1965;Chrzanowski et al, 1980;Stavert et al, 1986). Cigarette smokers serve as a very interesting population to study because of protective or maladaptive mechanisms which may develop in this population chronically exposed to relatively high levels of NO 2 .…”

“…Chronic obstructive pulmonary disease with emphysema or fibrosis is controversial and may be long-term sequelae of NO, exposure in animals (Stavert et al, 1986;Blank et al, 1988). Development of obstructive and/or restrictive pulmonary function tests and radiographic hyperinflation in humans suggest the development of chronic obstructive pulmonary disease, fibrosis and emphysema (Table 7).…”