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Iron Disequilibrium in the Rat Lung After Instilled Blood^*

^* From the National Health and Environmental Effects Research Laboratory, Environmental Protection Agency, Research Triangle Park, NC.

Correspondence to: Andrew J. Ghio, MD, National Health and Environmental Effects Research Laboratory, Environmental Protection Agency, Research Triangle Park, NC 27711

Study objectives: The extravasation of erythrocytes into the human lung occurs in a myriad of pulmonary disorders. Metal that is initially included in hemoglobin has been postulated to precipitate a disequilibrium in iron metabolism, to present an oxidative stress, and to contribute to tissue injury in several lung diseases. The objective of this study is to test the hypothesis that the tracheal instillation of blood in an animal model would have significant effects on iron equilibrium and would be associated with an injury to the lower respiratory tract.

Design: Rats were intratracheally instilled with either 1.0 mL saline solution (n = 36) or 1.0 mL blood (n = 36). Biochemical end points and histochemistry were obtained at times between 20 min and 14 days after the exposure to saline solution or blood.

Results: Total and nonheme iron concentrations in tracheal lavage fluid increased after the instillation of the blood. The percentage of neutrophils in the lavage fluid was elevated 1 day after the instillation of blood and remained at that level for at least 4 days following exposure, while protein concentrations were significantly increased at 1 day and 2 days only. Erythrocytes in the lung tissue were stained for hemoglobin immediately after exposure, but by 4 days after exposure, there was none. Ferritin was elevated between 1 day and 4 days after exposure, but by 7 days after exposure, the expression of this storage protein had returned to baseline values.

Conclusions: We conclude that intratracheal instillation of whole blood in the rat can induce a neutrophilic lung injury that is associated with a disruption of normal iron metabolism. This disruption of the iron equilibrium is made evident by quantifying iron and staining for hemoglobin and ferritin. All indexes of biological effect had corrected by 7 days after exposure.

Key Words: erythrocyte • hemoptysis • hemorrhage • lung diseases • oxidants.

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