ObjectiveTo evaluate the effects of high-frequency oscillation on the response to exogenous surfactant in lung-injured adult sheep.DesignA prospective, controlled,in vivo, animal laboratory study.SettingAnimal research facility of a health sciences university.SubjectsTwenty-eight adult sheep.InterventionsAnimals were anesthetized and instrumented with a tracheostomy and vascular catheters. Following whole lung saline lavage, animals were randomized to one of four groups: Group S-CMV received surfactant and was ventilated for 4 hrs using a conventional mechanical ventilation strategy, group S-HFOV/CMV received surfactant and was ventilated with a high-frequency oscillation technique for 2 hrs and a conventional mechanical strategy for 2 hrs, group HFOV/CMV underwent the latter ventilatory strategies without receiving surfactant, and group HFOV was ventilated with high-frequency oscillation only for 4 hrs. At the end of the ventilatory period, the distributions of ventilation and surfactant were evaluated in animals that received surfactant.Measurements and Main ResultsAnimals in the S-CMV group had a significantly greater mean Pao2value at the end of the experimental period than animals in the S-HFOV/CMV or HFOV/CMV groups. Evaluation of the distribution of ventilation relative to surfactant demonstrated that animals ventilated with high-frequency oscillation followed by conventional mechanical ventilation had a significantly greater disproportionate distribution of ventilation relative to surfactant compared with the CMV-only group.ConclusionsA period of high-frequency oscillation, as used in this study, immediately following exogenous surfactant administration mitigates the host’s response to surfactant when subsequently switched to conventional mechanical ventilation.