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

Author

Wang AY, Shen Y, Liew LJ, Wang JT, von Unge M, Atlas MD, and Dilley RJ

Subjects
Alkylating Agents pharmacology, Animals, Anti-Inflammatory Agents pharmacology, Chronic Disease, Male, Paper, Prostheses and Implants, Rats, Rats, Sprague-Dawley, Time Factors, Dexamethasone pharmacology, Disease Models, Animal, Mitomycin pharmacology, Tympanic Membrane surgery, Tympanic Membrane Perforation pathology, Wound Healing drug effects
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., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

Published
2015
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2. Searching for a rat model of chronic tympanic membrane perforation: Healing delayed by mitomycin C/dexamethasone but not paper implantation or iterative myringotomy

Author

Jeffrey T. Wang, Magnus von Unge, Rodney J. Dilley, Lawrence J. Liew, Yi Shen, Allen Y. Wang, and Marcus D. Atlas

Subjects
Male, Paper, medicine.medical_specialty, Alkylating Agents, Time Factors, Tympanic Membrane, medicine.medical_treatment, Mitomycin, Anti-Inflammatory Agents, Dexamethasone, Myringotomy, Rats, Sprague-Dawley, Myringoplasty, Otology, medicine, Animals, Tympanic Membrane Perforation, Wound Healing, business.industry, Mitomycin C, General Medicine, Prostheses and Implants, Tympanoplasty, Surgery, Rats, Disease Models, Animal, medicine.anatomical_structure, Otorhinolaryngology, Pediatrics, Perinatology and Child Health, Chronic Disease, Middle ear, business, medicine.drug
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.

Published
2015