title: Novel rat model of tympanostomy tube otorrhea.
abstract: OBJECTIVE
  Tympanostomy tube otorrhea (TTO), caused by the presence of pathogenic bacteria in the middle ear, is the most common complication of TT insertion. No studies have described a reproducible animal model of TTO. We aimed to develop a rat model of TTO which, in turn, could be used to assay the levels of TNF-α and IL-1β through the course of the infection.
  
  
  METHODS
  The left Eustachian tubes of 55 male Sprague-Dawley albino rats were occluded with gutta-percha (ETO=Eustachian Tube Occlusion). Middle ear (ME) effusion was ascertained by weekly otomicroscopy. At 3 weeks tympanostomy tubes were placed bilaterally and the MEs were inoculated bilaterally with Streptococcus pneumoniae through the tubes. The rats were randomly assigned to one of two daily ototopical treatments: ciprofloxacin/dexamethasone (CDX) or placebo. The animals in each of the two treatment groups were further divided to receive 1, 2, 5 or 7 days of treatment. The rats were sacrificed after treatment was finished. The rates of otorrhea, positive middle ear (ME) cultures, and levels of TNF-α and IL-1β in the ME fluid were measured.
  
  
  RESULTS
  Left ETO followed by ME inoculation with S. pneumoniae and treatment with placebo resulted in persistent infection (100% culture-positive ME fluid at 10 days) and otorrhea (85.7%). Persistent infection of the left ear was accompanied by significantly elevated the levels of IL-1β and TNF-α. Ears treated with CDX had lower rates of otorrhea at all time points and lower levels of IL-1β and TNF-α.
  
  
  CONCLUSIONS
  This study is the first to describe a reproducible animal model of acute TTO. Surgical obstruction of the ET, followed by TT placement and ME inoculation with S. pneumoniae induced persistent otorrhea and infection. Both IL-1β and TNF-α appear to be potential markers of persistent middle ear infection. This novel model may be used in future studies of the pathogenesis and therapy of TTO.
authors.affiliation: Department of Otolaryngology, University of Florida, Gainesville, FL 32610, USA. Rodrigo.Silva@ent.ufl.edu
authors.forename: Rodrigo C
authors.initials: RC
authors.lastname: Silva
authors.forename: Joseph E
authors.initials: JE
authors.lastname: Dohar
authors.forename: Patricia A
authors.initials: PA
authors.lastname: Hebda
mesh_terms: D000818:Animals; D000890:Anti-Infective Agents / Q000627:therapeutic use*; D002939:Ciprofloxacin / Q000627:therapeutic use*; D016207:Cytokines / Q000378:metabolism; D003907:Dexamethasone / Q000627:therapeutic use*; D004195:Disease Models, Animal; D005064:Eustachian Tube / Q000187:drug effects / Q000601:surgery; D018836:Inflammation Mediators / Q000378:metabolism; D053583:Interleukin-1beta / Q000378:metabolism; D008297:Male; D008876:Middle Ear Ventilation / Q000009:adverse effects* / Q000379:methods; D010034:Otitis Media with Effusion / Q000188:drug therapy* / Q000209:etiology; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D012016:Reference Values; D012307:Risk Factors; D012720:Severity of Illness Index; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D000890:Anti-Infective Agents; D016207:Cytokines; D018836:Inflammation Mediators; D053583:Interleukin-1beta; D014409:Tumor Necrosis Factor-alpha; D002939:Ciprofloxacin; D003907:Dexamethasone