Objectives: 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.
and results: 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.
Conclusion: 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.
AA = arachidonic acid; DBA = Dolichos biflorus agglutinin;
ELLA = enzyme-linked lectin assay; KHS = Krebs-Henseleit solution;
MARS = modified amphibian Ringer’s solution; MCTR = mucociliary
transportability; NDGA = nordihydroguaiaretic acid;
PBS = phosphate-buffered saline; PIC = protease inhibitor cocktail;
PLV = partial liquid ventilation; SI = secretory index