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This Article Full Text Full Text (PDF) All Versions of this Article: 293/3/R1342    most recent 00343.2007v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Borzone, G. Articles by Lisboa, C. Search for Related Content PubMed PubMed Citation Articles by Borzone, G. Articles by Lisboa, C.

ENVIRONMENTAL, EXERCISE AND RESPIRATORY PHYSIOLOGY

Rat and hamster species differences in susceptibility to elastase-induced pulmonary emphysema relate to differences in elastase inhibitory capacity

Departments of ¹Respiratory Diseases, ²Hematology and ³Diabetes and Metabolism and ⁴Medical Research Center, School of Medicine, Pontificia Universidad Católica de Chile; and ⁵Program of Pathology, Institute of Biomedical Sciences, Universidad de Chile, Santiago, Chile

Submitted 15 May 2007 ; accepted in final form 13 July 2007

Syrian Golden hamsters develop severe emphysema after a single intratracheal dose of elastase, whereas Sprague-Dawley rats exhibit mild emphysema with the same dose per kilogram body weight. We hypothesized that the development of severe emphysema is prevented in rats by the high serum level of 1-antitrypsin reported in rats, compared with hamsters, which provides for a high lung elastase inhibitory capacity (EIC). To explore this possibility, we challenged the antiprotease system of the rats by treating them with three similar weekly doses of elastase. Four months after treatment, we evaluated changes in histology, volume, and elastic properties of rat lungs and compared them with those of hamsters receiving a single dose of elastase. We also measured serum 1-antitrypsin levels and serum and lung EIC in control rats and hamsters. Results showed that, in association with 40% less serum and lung EIC compared with rats (P < 0.001), hamster lungs had upper-lobe bullae formation, severe microscopic emphysema, a fourfold increase in lung volume (P < 0.01) and a threefold increase in constant k, an index of compliance, of the lung deflation pressure-volume curve (P < 0.01). In contrast, rats developed mild emphysema, with only 50% increase in volume (P < 0.05) and 60% increase in constant k (P < 0.01). In conclusion, two species that differ in serum and lung EIC exhibit significant differences in emphysema development after elastase. Rats with high EIC, despite receiving three doses of elastase, showed significantly less derangement of morphological and physiological parameters than hamsters with low EIC receiving a single dose.

alpha1-antitrypsin; disease models; lung mechanics; susceptibility