Lung function, permeability, and surfactant composition in oleic acid-induced acute lung injury in rats

Kate G. Davidson, Andrew D. Bersten, Heather A. Barr, Kay D. Dowling, Terence E. Nicholas, Ian R. Doyle

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    72 Citations (Scopus)


    Although acute lung injury (ALI) is associated with inflammation and surfactant dysfunction, the precise sequence of these changes remains poorly described. We used oleic acid to study the pathogenesis of ALI in spontaneously breathing anesthetized rats. We found that lung pathology can occur far more rapidly than previously appreciated. Lung neutrophils were increased approximately threefold within 5 min, and surfactant composition was dramatically altered within 15 min. Alveolar cholesterol increased by ̃200%, and even though disaturated phospholipids increased by ̃30% over 4 h, the disaturated phospholipid-to-total phospholipid ratio fell. Although the alveolocapillary barrier was profoundly disrupted after just 15 min, with marked elevations in lung fluid (99mTc-labeled diethylenetriamine pentaacetic acid) and 125I-labeled albumin flux, the lung rapidly began to regain its sieving properties. Despite the restoration in lung permeability, the animals remained hypoxic even though minute ventilation was increased approximately twofold and static compliance progressively deteriorated. This study highlights that ALI can set in motion a sequence of events continuing the respiratory failure irrespective of the alveolar surfactant pool size and the status of the alveolocapillary barrier.

    Original languageEnglish
    Pages (from-to)L1091-L1102
    Number of pages12
    JournalAmerican Journal of Physiology - Lung Cellular and Molecular Physiology
    Issue number6
    Publication statusPublished - 1 Dec 2000


    • Alveolar protein
    • Alveolocapillary permeability
    • Lysophosphatidylcholine
    • Respiratory pathophysiology
    • Static lung compliance


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