BACKGROUND: To compare the combined effects of arteriovenous extracorporeal lung assist (AV-ECLA) and high-frequency oscillatory ventilation (HFOV) on pulmonary gas exchange, hemodynamics, and respiratory parameters in a lavage-induced porcine lung injury model. METHODS: A prospective, randomized animal study. Saline lung lavage was performed in 33 healthy female pigs, weighing 52 +/- 4.1 kg (mean +/- SD), until the Pao2 decreased to 53 +/- 8 mm Hg. After a stabilization period of 60 minutes, the animals were randomly assigned to four groups: group 1, pressure-controlled ventilation (PCV) with a tidal volume of 6 mL/kg; group 2, PCV with a tidal volume of 6 mL/kg and AV-ECLA; group 3, HFOV; group 4, HFOV and AV-ECLA. In groups 2 and 4, the femoral artery and vein were cannulated and a low-resistance membrane lung was interposed. After isolated evaluation of AV-ECLA, the mean airway pressure was increased by 3 cm H2O from 16 to 34 cm H2O every 20 minutes, accompanied by blood gas analyses and measurements of respiratory and hemodynamic variables. RESULTS: Only in AV-ECLA-treated animals was normocapnia achieved. No significant increase of Pao2 attributable to AV-ECLA alone was detected. Mean airway pressure augmentation resulted in a significant increase in Pao2 in all groups. Peak inspiratory pressure was significantly lower in HFOV-treated animals. CONCLUSIONS: The combination of AV-ECLA and HFOV resulted in normocapnia and comparable Pao2, although a smaller ventilator pressure amplitude was applied. Long-term animal studies are needed to assess whether this approach results in further lung protection.