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Introduction: The application of perfluorohexane (PFH) vapor led to an improvement of oxygenation and mechanical lung function in a model of oleic acid-induced ARDS in sheep. The aim of this study was to investigate the effects of PFH on gas exchange over an extended time period and to reduce the invasiveness of ventilation., Method: ARDS was induced in sheep ( n=12) by injecting 0.1 ml/kg body weight oleic acid intravenously. Six sheep were treated for 30 min with 18 vol.% PFH (PFH-Tx) and followed up over a time period of 240 min while untreated sheep ( n=6) served as controls. Subsequently the F(I)O(2) was reduced to generate a p(a)O(2) between 100-140 mmHg. Gas exchange, respiratory and hemodynamic data were collected at regular intervals. Data were analysed using covariance analysis., Results: PFH treatment led to an improvement in oxygenation ( p<0.01) and in mechanical lung function ( p<0.01). Furthermore, mean pulmonary artery pressure ( p<0.01) and shunt ( p<0.01) were lower in PFH-Tx. F(I)O(2) could be reduced in all PFH-treated animals ( p<0.01)., Conclusion: Treatment of oleic acid-induced lung injury with PFH vapor improved oxygenation and mechanical lung function over a extended time period allowing a reduction in the invasiveness of ventilation.