Hyperoxia-Induced Alterations of Rat Alveolar Lavage Composition and Properties

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Abstract
Although lethal exposures of most animal species to oxygen result in a reduced amount of surfactant phospholipids (PL), hyperoxia in rats leads to elevated levels of PL on the alveolar surface. Because of this different response, a study was made of the amount, composition, surface properties, and subfraction distribution (obtained by differential centrifugation) of alveolar lavage materials from rats exposed to >95% oxygen for 64 h. The exposures lead to severe lung damage, which includes the appearance of pleural effusion, pulmonary edema, and increased protein levels on the alveolar surface. However, the PL levels of lavage fluid are increased two-to threefold, and the PL composition is altered. In O2-exposed rats, only 39(±1)% of the phospholipid is disaturated phosphatidylcholine (DSPC), the major surface active component of surfactant, as compared to 46(±1)% DSPC in lavage from control animals. The distribution of PL and DSPC in subfractions of lavage materials obtained by differential centrifugation is approximately reversed following hyperoxia. In lavage from control anitnab, 36% of the PL is in the heavier, more dense subfractions and 647c is in the lighter, less dense subfractions, while 72% is heavier and 28% lighter in lavage from O2-exposed animals. Measurements of surf ace properties with the Wilhelmy balance indicate that the ability of the lavage materials to reduce surface tension is impaired following hyperoxia. Thus, lethal exposures of rats to oxygen lead to increased amounts of surfactant on the alveolar surface, but the surface properties of the surfactant are impaired, probably due to reduced levels of DSPC, increased amounts of protein, and alterations in its physical form.