Rat model of chronic tympanic membrane perforation: Ventilation tube with mitomycin C and dexamethasone

Int J Pediatr Otorhinolaryngol. 2016 Jan:80:61-8. doi: 10.1016/j.ijporl.2015.11.010. Epub 2015 Nov 25.

Abstract

Objective: Chronic tympanic membrane perforation (TMP) in a clinical setting may attract surgical intervention. With the advent of modern biomaterials, new options are available for myringoplasty but safety and efficacy need evaluation in a chronic TMP animal model. The aim of this study was to evaluate the efficacy of ventilation tube (VT) insertion in conjunction with topical application of mitomycin C/dexamethasone (M/D) for the creation of chronic TMP in rats.

Methods: Thirty male Sprague-Dawley rats underwent myringotomy of the right tympanic membrane (TM) and were divided into three experimental groups: spontaneous healing (myringotomy control), VT insertion for 2 weeks and VT insertion for 2 weeks in conjunction with topical application of M/D (VT-M/D). All TMs were regularly assessed by otoscopy for 10 weeks and then animals were sacrificed for histological evaluation.

Results: In the VT-M/D group, seven out of ten (70%) perforations were patent at 10 weeks (mean patency, 57.9 days; P<0.01). The VT group had two out of ten (20%) perforations patent at 10 weeks (mean patency, 26.5 days; P<0.01), while all TMPs from the myringotomy control group were closed by day 9 (mean patency, 7.2 days). Histologically, the TMPs patent at week 10 had a stratified squamous epithelialized rim, keratinocyte layer thickening around the perforation edge as well as increased collagen deposition and macrophage infiltration.

Conclusion: Chronic TMP in a rat model was successfully created by VT insertion and the efficacy was increased in combination with topical application of M/D.

Keywords: Animal model; Chronic; Dexamethasone; Mitomycin C; Tympanic membrane perforation; Ventilation tube.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Topical
  • Animals
  • Anti-Inflammatory Agents / pharmacology
  • Chronic Disease
  • Dexamethasone / pharmacology
  • Disease Models, Animal*
  • Male
  • Middle Ear Ventilation
  • Mitomycin / pharmacology
  • Myringoplasty
  • Nucleic Acid Synthesis Inhibitors / pharmacology
  • Otoscopy
  • Rats
  • Rats, Sprague-Dawley
  • Tympanic Membrane / drug effects*
  • Tympanic Membrane / surgery*
  • Tympanic Membrane Perforation / pathology*
  • Wound Healing / drug effects*

Substances

  • Anti-Inflammatory Agents
  • Nucleic Acid Synthesis Inhibitors
  • Mitomycin
  • Dexamethasone