Dose response to aerosolized perflubron in a neonatal swine model of lung injury.
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).
Kandler
Michael Andreas
MA
Universitätsklinik für Kinder und Jugendliche, Loschgestrasse 15, 91054 Erlangen, Germany. michael.kandler@web.de
von der Hardt
Katharina
K
Gericke
Nelly
N
Chada
Martin
M
Dötsch
Jörg
J
Rascher
Wolfgang
W
D000818:Animals; D000831:Animals, Newborn; D005617:Chlorofluorocarbons, Methane / Q000008:administration & dosage; D003287:Contrast Media / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004655:Emulsions / Q000378:metabolism; D005466:Fluorocarbons / Q000494:pharmacology*; D006801:Humans; D006842:Hydrocarbons, Brominated; D007375:Interleukin-1 / Q000235:genetics / Q000378:metabolism; D008168:Lung / Q000187:drug effects* / Q000276:immunology; D055370:Lung Injury; D011663:Pulmonary Surfactants / Q000378:metabolism; D011897:Random Allocation; D013552:Swine
D005617:Chlorofluorocarbons, Methane; D003287:Contrast Media; D004655:Emulsions; D005466:Fluorocarbons; D006842:Hydrocarbons, Brominated; D007375:Interleukin-1; D011663:Pulmonary Surfactants; C003072:perflubron