Chronic interstitial pulmonary fibrosis produced in hamsters by endotracheal bleomycin: pathology and stereology.

Abstract

An animal model of chronic interstitial pulmonary fibrosis was produced in male golden hamsters by a single endotracheal instillation of 0.5 unit of bleomycin per 100 g of body weight. Interstitial edema and polymorphonuclear cell infiltration during the early days were followed by marked al­ veolar and bronchiolar epithelial cell proliferation, interstitial pulmonary fibrosis, and predomi­ nance of round cell response, which reached a peak at approximately 30 days. The process then waned slowly, attaining stability at 90 days; foci of chronic interstitial fibrosis with round cell in­ filtration were still found in all animals at 180 days. The mortality rate was 17 per cent, with deaths occurring up to day 41; most animals died in the early stages. A lung disease index was measured stereologically by scanning 3 lung sections from each animal with a grid and determining the percentage of lung that was diseased, irrespective of the nature of the disease process. Mean values of the index at 8, 30, 60, 90, and 180 days after bleomycin were: 21.7, 40.3, 28.2,12.1, and 13.0 per cent, respectively; all of these values were significantly different from the control value of 1.1 per cent (P < 0.001). In 25 animals treated with bleomycin, the coefficients of correlation between the disease index and lung compliance, vital capacity, inspiratory capacity, and total lung capacity determined physiologically, were -0.63, -0.68, and -0.43, respectively. We conclude that this ani­ mal model of interstitial pulmonary fibrosis should be of value in studying cellular and biochemi­ cal events in the lung and in exploring various therapeutic strategies.