title: The role of gastric and duodenal agents in laryngeal injury: an experimental canine model.
abstract: OBJECTIVE
  The specific agents responsible for producing laryngeal signs and symptoms are currently unknown. We systematically evaluated the damaging role of gastric (acid and pepsin) and duodenal (bile acids and trypsin) ingredients individually and in combination on different laryngeal structures in an experimental canine model.
  
  
  METHODS
  A total of 42 beagles were studied (wt 9-15 kg each). After pentathol anesthesia all dogs underwent laryngoscopy. Injury (punch biopsy) was caused to the right vocal cord, medial arytenoid wall, and posterior cricoid wall on day 1. Pepsin (0.5 mg/ml), conjugated bile acid (CBA) (ursodeoxycholic acid, 300 micromolar), unconjugated bile acids (UBA) (cholic, 300 micromolar), trypsin (0.5 mg/ml) at pH 1-2, 4-5, and 6-7 were applied bilaterally to laryngeal sites three times per week for a total of 9-12 applications. Changes in laryngeal sites were scored visually. All dogs were sacrificed 1 day post last application. Laryngeal tissue was harvested and sent for blinded pathological examination. Histologic and visual scores were compared to each other and to control- and sham-treated dogs.
  
  
  RESULTS
  Pepsin alone (8.5 +/- 1.66) or combined with CBA (16.63 +/- 1.66) at pH 1-2 resulted in significant (p < 0.001) severe histological inflammation much greater than with other agents. Duodenal ingredients caused no or minimal degree of histological damage at all pH values. Visual scores above subtle erythema were significantly (p < 0.001) higher in the animals exposed to pepsin followed by CBA alone or in combination with pepsin at pH 1-2. There was a significant (p < 0.01) correlation between histology and visual scores (rho = 0.47; 95% CI = 0.30-0.60) for all sites combined. Of the three laryngeal sites, vocal cords were the most sensitive to injury by applied solutions.
  
  
  CONCLUSIONS
  (i) In acidic refluxate, pepsin and CBAs are the most injurious agents affecting laryngeal tissue. (ii) Duodenal agents do not play a significant role in causing laryngeal injury. (iii) Aggressive acid suppression should eliminate the injurious potential of any gastroduodenal refluxate.
authors.affiliation: Department of Gastroenterology and Hepatology, Center for Swallowing and Esophageal Disorders, Cleveland Clinic Foundation, Cleveland, Ohio 44195, USA.
authors.forename: Talal
authors.initials: T
authors.lastname: Adhami
authors.forename: John R
authors.initials: JR
authors.lastname: Goldblum
authors.forename: Joel E
authors.initials: JE
authors.lastname: Richter
authors.forename: Michael F
authors.initials: MF
authors.lastname: Vaezi
mesh_terms: D000818:Animals; D001647:Bile Acids and Salts / Q000494:pharmacology; D002756:Cholagogues and Choleretics / Q000494:pharmacology; D004285:Dogs; D005764:Gastroesophageal Reflux / Q000150:complications* / Q000473:pathology; D007818:Laryngeal Diseases / Q000209:etiology* / Q000473:pathology; D007830:Larynx / Q000187:drug effects / Q000473:pathology; D010434:Pepsin A / Q000494:pharmacology; D014357:Trypsin / Q000494:pharmacology; D014580:Ursodeoxycholic Acid / Q000494:pharmacology; D014827:Vocal Cords / Q000187:drug effects / Q000473:pathology
chemical_list: D001647:Bile Acids and Salts; D002756:Cholagogues and Choleretics; D014580:Ursodeoxycholic Acid; D014357:Trypsin; D010434:Pepsin A