Early effects of intratracheal instillation of elastase on mortality, respiratory function, and pulmonary morphometry of F-344 rats

Journal Article · Fri Jan 01 00:00:00 EST 1982 · Toxicol. Appl. Pharmacol.; (United States)

DOI:https://doi.org/10.1016/0041-008X(82)90243-5· OSTI ID:6096365

Damon, E G; Mauderly, J L; Jones, R K

Rats were intratracheally instilled with purified elastase at doses ranging from 0.3 to 1.6 IU/g of body weight to induce pulmonary emphysema. In 50 rats exposed to elastase at doses ranging from 0.3 to 1.6 IU/g, the LD/sub 50/ was approximately 1.2 IU/g. A mortality of 9% occurred in 94 rats instilled with a dose of 1.0 IU/g. Pulmonary function tests were conducted on nine surviving rats 2 to 4 weeks after instillation of elastase at doses ranging from 0.8 to 1.2 IU/g and on 20 untreated controls. The treated rats exhibited significant differences in pulmonary function similar to those observed in human emphysema. In rats treated at dose of 1.0 or 1.2 IU/g, histopathological studies showed there was an extensive loss of alveolar fine structure resulting in alveolar spaces ranging from 3 to 10 times the size of those in untreated control rats. Morphometric measurements of the mean linear intercepts of the alveolar septa confirmed these findings. Since the changes in pulmonary function and structure in rats treated with elastase at a dose of 1.0 IU/g body weight were consistent with changes observed in human patients with pulmonary emphysema, and since the mortality rate of 9% was considered acceptable, this dose was selected for use in subsequent studies requiring an animal model of emphysema.

• Research Organization: Inhalation Toxicology Research Inst., Albuquerque, NM
• DOE Contract Number: AC04-76EV01013
• OSTI ID: 6096365
• Journal Information: Toxicol. Appl. Pharmacol.; (United States), Vol. 64
• Country of Publication: United States
• Language: English

Related Subjects

59 BASIC BIOLOGICAL SCIENCES
EMPHYSEMA
BIOLOGICAL MODELS
HYDROLASES
INTRATRACHEAL ADMINISTRATION
BIOLOGICAL EFFECTS
DYNAMIC FUNCTION STUDIES
EXPERIMENTAL DATA
LUNGS
MORPHOLOGICAL CHANGES
MORTALITY
PATHOLOGY
RATS
ANIMALS
BODY
DATA
DISEASES
ENZYMES
INFORMATION
MAMMALS
NUMERICAL DATA
ORGANS
RESPIRATORY SYSTEM
RESPIRATORY SYSTEM DISEASES
RODENTS
VERTEBRATES
551000* - Physiological Systems
550900 - Pathology