18 Aug

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

Perfluorooctyl Bromide (Perflubron) Stimulates Mucin Secretion in the Ferret Trachea: ConclusionThe antioxidant NDGA is able to block directly and rapidly both the lipoxygenase and cyclooxygen-ase pathways, and NDGA suppressed mucin secretion both immediately (at 40 min) and after 4 h. Methylprednisolone only appeared to exert an effect after 4 h of incubation and did not show any effect at 40 min. Physiologically, methylprednisolone has a latent period for effects to be demonstrated, as this pathway of phospholipase A inhibition is mediated through lipocortin generation, which is time-depen-dent.
At the end of perflubron exposure, the bathing fluid around the tracheal segment was changed from KHS to perflubron. A change of microenvironment from liquid to air occurs because perflubron evaporates faster than KHS. This could stimulate secretion directly by mechanical changes in the epithelium or secondarily by stimulating AA metabolism.
After 4 h of perflubron plus evaporation, atropine and methylprednisolone partially inhibited, and NDGA and PIC completely inhibited, the increased mucin secretion. As expected, there was no inhibition of secretion with a- or ^-adrenergic receptor antagonists. The partial inhibition by atropine suggests the involvement of cholinergic mediators activated by mechanical stimulation of the epithelium Reading here buy ventolin inhaler. The protease inhibitors were chosen to inhibit the kinin pathway and complement the system rather than to inhibit proteolytic secretagogues, such as elastase, because the healthy tracheal tissue of these animals should be relatively free of proteases, and components of the kinin pathway can be activated in response to physical stimulus. These data are also most consistent with a role for AA metabolites in producing the observed secretory effect.
Extrapolating these results to the clinical setting should be done carefully, as these studies were conducted in healthy ferret tracheal tissue, whereas PLV is used in patients with respiratory failure and often with airway inflammation. However, if the principal secretagogue effect is due to generation of AA metabolites, this effect might be even more pronounced in the inflamed airway.
It is unlikely that the generation of AA metabolites is the only cause of the increase in secretions noted during PLV, because locally generated metabolites of AA probably would be washed away during the course of PLV. A primary role for perflubron lifting and mobilizing mucus that is present on the airway surface is experimentally suggested by the greater initial increase (86%) in mucin noted at 40 min of exposure with less difference (18%) between perflubron and KHS after 4 h of incubation with no evaporation. Together, these data suggest that the mucus mobilization and secretion-modifying effect is not directly harmful and can be partially inhibited by phospholipase A inhibitors. Although these experiments were not designed to evaluate any potential therapeutic benefits of mucus mobilization or secretion by perflubron, the results lend some support to the speculation that perflubron might be beneficial for airway clearance in patients with profound airway obstruction due to impacted secretions.

Categories: Perfluorooctyl Bromide
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