Searching for a rat model of chronic tympanic membrane perforation: Healing delayed by mitomycin C/dexamethasone but not paper implantation or iterative myringotomy

Allen Wang, Y. Shen, Lawrence Liew, J.T. Wang, M. Von Unge, Marcus Atlas, Rodney Dilley

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    19 Citations (Scopus)

    Abstract

    Objectives: Surgical intervention such as myringoplasty or tympanoplasty is an option in the current clinical management of chronic tympanic membrane perforation (TMP). Animal models of chronic TMP are needed for pre-clinical testing of new materials and to improve existing techniques. We evaluated several reported animal model techniques from the literature for the creation of chronic TMPs. The aim of this study was to evaluate production of chronic TMPs in a rat model using topical mitomycin C/dexamethasone, paper insertion into middle ear cavity (MEC) or re-myringotomy.
    Methods: Forty male Sprague-Dawley rats underwent myringotomy of the right tympanic membrane (TM) and were randomly divided into 3 experimental groups: application of topical mitomycin C/dexamethasone, paper insertion into middle ear cavity, or re-myringotomy. Control perforations were allowed to close spontaneously. TMs were assessed regularly with otoscopy for 8 weeks. At the end of 8 weeks, animals were sacrificed for histology.
    Results: The closure of TMPs was significantly delayed by mitomycin C/dexamethasone (mean patency, 18.9 days; P≤. 0.01) compared with the control (mean patency, 7 days), but was not significantly delayed in the paper insertion group (mean patency, 9.4 days; P= 0.74). Repeated myringotomy of closed perforations (mean number of myringotomies, 8.9 per ear) stimulated acceleration of closure rather than delay. Histologically, the mitomycin C/dexamethasone group had almost normal TM morphology, while the paper insertion group revealed inflammatory and granulomatous responses. The re-myringotomy group had a thickened TM fibrous layer with collagen deposition. Conclusions: Mitomycin C/dexamethasone delayed TMP closure in rats but the effect was not sufficiently long-lasting to be defined as a chronic TMP. Neither paper insertion into middle ear cavity nor re-myringotomy created chronic TMP in rats.
    Original languageEnglish
    Pages (from-to)1240-1247
    JournalInternational Journal of Pediatric Otorhinolaryngology
    Volume79
    Issue number8
    Early online date26 May 2015
    DOIs
    Publication statusPublished - Aug 2015

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