Dose Response to Aerosolized Perflubron in a Neonatal Swine Model of Lung Injury

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Abstract
Aerosolized perfluorocarbon (PFC) improves gas exchange, lung mechanics, and pulmonary artery pressure. The objective of this intervention was to study the dose-response effect to aerosolized perfluorooctylbromide (PFOB; perflubron, LiquiVent, Alliance Pharmaceutical Corp.) in surfactant-depleted piglets. After induction of lung injury by saline lavage, 25 newborn piglets were randomly assigned to receive 0, 1.25, 2.5, 5.0, or 7.5 mL/kg aerosolized PFOB per hour. A 2-h therapy period was followed by a 3-h observation period. In all animals, respiratory support was performed with intermittent mandatory ventilation. After aerosol treatment and 3 h of observation, arterial oxygen pressure was similarly improved in the 2.5-, 5.0-, and 7.5-mL·kg−1·h−1 aerosol-PFOB groups and higher compared with the 1.25-mL·kg−1·h−1 aerosol-PFOB (P < 0.01) and the control groups (P < 0.001). Compared with the control group, arterial carbon dioxide pressure was significantly reduced with 2.5-, 5.0-, and 7.5-mL·kg−1·h−1 aerosol-PFOB (P < 0.001). Treatment with 1.25 mL·kg−1·h−1 aerosol-PFOB did not significantly affect arterial carbon dioxide pressure. The 20% terminal dynamic compliance/dynamic compliance was significantly improved in the groups that received 2.5, 5.0, and 7.5 mL·kg−1·h−1 aerosol-PFOB compared with control animals. Mean pulmonary artery pressure was lower after therapy with 5.0 and 7.5 mL·kg−1·h−1 aerosol-PFOB (P < 0.01) than in the control group. IL-1β gene expression in lung tissue was significantly reduced with PFOB 1.25 mL·kg−1·h−1. In summary, aerosolized PFOB improved terminal dynamic compliance, pulmonary gas exchange, and pulmonary artery pressure in a dose-dependent manner. In terms of oxygenation and lung mechanics, the optimum dose was between 2.5 and 5 mL·kg−1·h−1.