The lung of the copper-deficient rat. A model for developmental pulmonary emphysema.
Based on the hypothesis that cross-linked elastin is critical for normal lung structure, lung tissue from copper-deficient rats was studied. Copper deficiency was induced in the second generation by feeding dams a milk-based diet low in copper (less than 1 ppm) during gestation and lactation. The weanlings were fed the same diet until they showed severe signs of deficiency between 6 and 10 weeks of age. Controls animals received the basal diet supplemented with 10 ppm copper. Liver cytochrome oxidase activity, which served as the chief index of deficiency, decreased from a normal level of approximately 80 to 15 mumole/min/g. The lungs of the deficient animals contained 17% less elastin and had 35% larger alveolar spaces (34.7 vs 47.7 intercepts), as determined by the mean alveolar intercept method. The ultrastructure of elastin in the bronchi, arterioles, and alveolar ducts had a "washed out" appearance. To determine the reversibility of the pathology, deficient animals, 5 to 10 weeks of age, were repleted by feeding a copper-supplemented diet for 1, 2, and 3 months. During this period growth resumed, anemia disappeared, and liver cytochrome oxidase returned to normal. There was no improvement in lung structure with regard to alveolar size (28.4 intercepts compared with 43.6 in controls and 35.1 in deficient littermates killed at the start of repletion). The ultrastructure and electron density of pulmonary elastin was restored to near normal. The lung of the copper-deficient rat is proposed as a model for developmental pulmonary emphysema.
D000818:Animals; D001160:Arterioles / Q000648:ultrastructure; D001980:Bronchi / Q000648:ultrastructure; D003300:Copper / Q000172:deficiency*; D004032:Diet; D004195:Disease Models, Animal; D004549:Elastin / Q000378:metabolism; D003576:Electron Transport Complex IV / Q000378:metabolism; D005260:Female; D008099:Liver / Q000201:enzymology; D008168:Lung / Q000648:ultrastructure*; D008297:Male; D011650:Pulmonary Alveoli / Q000648:ultrastructure; D011656:Pulmonary Emphysema / Q000473:pathology; D051381:Rats; D011919:Rats, Inbred Strains
D003300:Copper; D004549:Elastin; D003576:Electron Transport Complex IV