Perfluorooctyl Bromide (Perflubron) Stimulates Mucin Secretion in the Ferret Trachea

Abstract

Partial liquid ventilation with perfluorooctyl bromide (perflubron) has been shown to be safe and effective in animal models with respiratory failure. However, airway mucus accumulation has been reported to be a problem in human trials. We hypothesized that this might be because perflubron directly affects mucociliary clearance or stimulates mucus secretion. We first measured the mucociliary transportability of secretions on the mucus-depleted frog palate exposed to perflubron and demonstrated that the ciliated epithelium remained intact with preservation of mucociliary transport. We then measured mucin and lysozyme secretion from isolated ferret tracheal segments to evaluate the secretagogue potential of perflubron. There was an 86% increase in mucin secretion with perflubron incubation at 40 min (n = 19; p < 0.01) and a 52% increase after 4 h of exposure followed by evaporation of perflubron (n = 19; p < 0.01). There was no significant difference in lysozyme secretion at any time between perflubron-exposed or buffer-exposed tissue (n = 4). The secretagogue effect was completely blocked by nordihydroguaiaretic acid, an inhibitor of arachidonic acid (AA) metabolism. These data suggest that although perflubron does not seem to be harmful to the airway, it induces mucus secretion in a noninflamed airway, and that this can be modulated by inhibitors of AA metabolism.