Laryngeal mucosa: its susceptibility to damage by acid and pepsin.
OBJECTIVE
Exposure of pig laryngeal mucosa to pepsin and acid will have a differential damaging effect depending on the anatomical site, mirroring the effects seen in the human larynx in laryngopharyngeal reflux (LPR). This study aims to quantitate damage caused to laryngeal tissue by acid alone, and acid and pepsin, and also to determine if the extent of this damage depends on the tissue site.


METHODS
Prospective translational research study.


METHODS
An excised porcine laryngeal damage model in a small Ussing chamber was used to measure the effect of pepsin and acid on five sites (ventricles, vocal folds, posterior commissure, supraglottic, and subglottic mucosa). The tissue samples were incubated on the lumenal side for 1 hour with pH 2 and 4 HCl, pH 2 plus 1 mg/mL pepsin, and pH 4 plus 1 mg/mL pepsin. Damage was assessed by changes in absorbance of the bathing solution at optical density (OD) 260 nm and OD 280 nm and by measurement of released DNA compared to tissues bathed in pH 7.4 buffer. Damage was also assessed histologically.


RESULTS
Based on histology, all the tissues were resistant to pH 4.0 except the subglottic mucosa. Only the posterior commissure was not damaged by pH 2.0 plus pepsin. Similar patterns were observed with absorbance changes and DNA release.


CONCLUSIONS
The subglottic mucosa was the most susceptible to damage and the posterior commissure the least. Laryngeal tissues are essentially resistant to damage at pH 4.0, but are damaged when pepsin is present. This suggests that in LPR, pH 4.0 or above refluxate would only be damaging if it contains pepsin.
Bulmer
David M
DM
Institute for Cell and Molecular Biosciences, The Medical School, Newcastle University, Framlington Place, Newcastle upon Tyne, United Kingdom.
Ali
Mahmoud S
MS
Brownlee
Iain A
IA
Dettmar
Peter W
PW
Pearson
Jeffrey P
JP
D000818:Animals; D004195:Disease Models, Animal; D005744:Gastric Acid / Q000378:metabolism*; D006863:Hydrogen-Ion Concentration; D007820:Laryngeal Mucosa / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D057045:Laryngopharyngeal Reflux / Q000209:etiology / Q000378:metabolism / Q000473:pathology*; D007830:Larynx / Q000378:metabolism / Q000473:pathology / Q000601:surgery; D010434:Pepsin A / Q000009:adverse effects* / Q000378:metabolism; D011446:Prospective Studies; D013552:Swine
D010434:Pepsin A