Dose response to aerosolized perflubron in a neonatal swine model of lung injury.

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-1beta 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).

• Authors: Michael Andreas Kandler, Katharina von der Hardt, Nelly Gericke, Martin Chada, Jörg Dötsch, Wolfgang Rascher
• Journal: Pediatric research (Pediatr Res) Vol. 56 Issue 2 Pg. 191-7 (Aug 2004) ISSN: 0031-3998 [Print] United States
• PMID: 15181181 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Chlorofluorocarbons, Methane
• Contrast Media
• Emulsions
• Fluorocarbons
• Hydrocarbons, Brominated
• Interleukin-1
• Pulmonary Surfactants
• perflubron

Topics

• Animals
• Animals, Newborn
• Chlorofluorocarbons, Methane (administration & dosage)
• Contrast Media (pharmacology)
• Dose-Response Relationship, Drug
• Emulsions (metabolism)
• Fluorocarbons (pharmacology)
• Humans
• Hydrocarbons, Brominated
• Interleukin-1 (genetics, metabolism)
• Lung (drug effects, immunology)
• Lung Injury
• Pulmonary Surfactants (metabolism)
• Random Allocation
• Swine