Pathologic Changes in Rat Lungs Following Acute Sulfur Mustard Inhalation

Abstract

Although the majority of deaths resulting from exposure to sulfur mustard (HD) have been due to pulmonary dysfunction, there are no detailed accounts of the pathogenesis of HD-induced lesions in the respiratory tract. Accordingly, we investigated the early changes within the trachea and lungs of rats following inhalation exposure to HD. Anesthetized rats were exposed by intratracheal intubation to vaporized HD (0.35 mg in 100 m l absolute ethanol) or ethanol alone for 50 min. Animals were euthanatized at 0, 1, 4, 6, 12, 18, and 24 h postexposure (PE), and their respiratory tracts were prepared for histological and ultrastructural examination. In rats exposed to HD, multifocal, petechial hemorrhages were grossly evident on the pleural surface of the lung at 6 h PE. Atelectasis and edema of the accessory lobe occurred at 12-18 h PE. Histologically, lesions in the respiratory tract were confined primarily to the trachea, bronchi and larger bronchioles. In HD-exposed rats, there was a progressive depletion of the bronchiolar-associated lymphoid tissue (BALI), with necrosis of the lymphoid cells as early as 12 h PE. Necrosis and sloughing of the tracheal and bronchial epithelia at 6-12 h PE was followed by the formation of fibrinous pseudomembranes within the bronchi. Necrosis and separation of airway epithelia occurred at the mucosal/submucosal interface. Pseudomembranes formed almost exclusively in deepithelialized areas overlying the BALT. Cartilaginous lesions, characterized by necrosis of individual chondrocytes, were evident at 12 h PE. Pulmonary edema and occasional alveolar hemorrhage occurred from 18 to 24 h PE. Small bronchioles and alveoli were relatively unaffected, and only a few inflammatory cells were observed at any time.