Decreased reactivity to inhaled methacholine after intratracheal instillation of hard metal.
Fedan-JS; Kimmineni-C; Rengasamy-A
Am J Respir Crit Care Med 1998 Mar; 157(3)(Suppl):A144
Inhalation of hard metal (HM) is associated with the development of interstitial alveolitis, fibrosis and asthma. We examined in rats the effects of an industrial HM mixture on reactivity of conscious animals to inhaled methacholine (MCh) aerosol (0.3 - 30 mg/ml). Using whole body plethysmography and enhanced pause (Penh) as an index of obstruction, MCb dose-response curves were obtained before the i.t. administration of HM (2.5, 5 and 10 mg per 100 g) or saline, and after (6 - 7.S hr and 30 - 31 hr) treatment. Following HM-treatment, basal Penh became significantly elevated by 30 - 31 hr. HM caused progressive (P<0.05) decreases in reactivity to MCh over the measuring period, while only a slight reduction (at 3 mg/m1 MCh) was seen after saline administration. Histological examination of lungs after HM showed little changes after 8 hr; at the later time point there was acute inflammation protein leakage (edema and fibrin strands in the alveoli) at the site of deposition as well as at distant locations. No histopathological changes were seen in the bronchi, bronchioles and alveolar ducts. These observations are suggestive of the initiation of alveolitis rather than asthma-related airway hyperreactivity.
Methacholines; Hard-metals; Fibrosis; Bronchial-asthma; Aerosol-particles; Aerosols; Laboratory-animals; Animal-studies; Animals; Pulmonary-system-disorders; Alveolar-cells; Respiratory-system-disorders; Plethysmographs; Plethysmography; Histology
American Journal of Respiratory and Critical Care Medicine