Pulmonary hemodynamics and lung function during chronic paraquat poisoning in sheep. Possible role of reactive oxygen species.

The purpose of this study was to establish a chronic model of paraquat-induced lung injury. To examine the role of reactive oxygen species in this form of lung injury, we measured malondialdehyde (MDA) and superoxide dismutase (SOD) activity in the lungs. Paraquat (5 mg/kg intramuscularly) caused a significant decrease in dynamic lung compliance from 128.5 +/- 9.2 to 63.3 +/- 11.8 ml/cm H2O (p less than 0.05), with a significant increase in AaPO2 3 wk after paraquat. Histologic findings in the lungs showed a gradual increase in the number of granulocytes and alveolar wall thickening with proliferation of reticular fibers and were coincident with the changes in physiology. A transient decrease in pressor responses to hypoxia was observed 1 wk after paraquat, although pulmonary hemodynamics did not change. The amount of lung MDA 3 wk after paraquat increased from the baseline value of 0.73 +/- 0.04 to 1.12 +/- 0.10 nmol/mg protein (p less than 0.05). SOD activity in the lung tissue significantly decreased from 6.47 +/- 0.20 to 4.82 +/- 0.25 U/mg protein (p less than 0.05) 1 wk after paraquat and remained at low levels for 3 wk. These findings suggest that a small dose of paraquat causes chronic lung injury characterized by granulocyte infiltration and lung fibrosis. Reactive oxygen species may play an important role in this chronic lung injury, and the inability to increase antioxidant defense may contribute to the reaction.