Otolaryngology - Theses
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ItemPrinciples of inner ear pharmacotherapy and its application to residual hearing protection in cochlear implantation: an animal model of residual hearing protection using locally delivered dexamethasone( 2011)BACKGROUND: There is growing experimental evidence to support that targeted application of steroid to the inner ear can ameliorate hearing loss resulting from the trauma of cochlear implantation in experimental animals. However, it is yet to be elucidated which factors in cochlear pharmacodynamics are more important in influencing protection, and whether the hearing protection achieved is long-term. This experimental project was designed to firstly confirm previous experimental observation that a single dose of steroid applied locally to a guinea pig cochlea can protect hearing, and then to assess whether such protection is sustained over a long term by following the animals up for 3 months. Furthermore, the study groups were designed to assess which variable between the duration of the application and the size of the applied dose is more important in therapeutic efficacy in terms of better and broader hearing protection. The results may be useful in helping to design a more clinically appropriate and adaptable treatment protocol in cochlear implantation surgery. METHODS: Dexamethasone or saline (control) was absorbed into a disc of polymeric sponge (Seprapack TM) and applied to the round window of adult guinea pigs prior to electrode implantation. The treatment groups were 2% (w/v) dexamethasone applied for 120 minutes; and 20% (w/v) applied for 30 minutes prior to the electrode implantation. Auditory sensitivity was determined pre-operatively and at 1 week, 4 weeks, 8 weeks and 12 weeks for all animals using pure-tone auditory brainstem response audiometry (2 – 32 kHz). Cochlear implantation was performed via a cochleostomy drilled into the basal turn of the cochlea, into which a miniature Sialistic electrode array was inserted using soft-surgery techniques. RESULTS: The implantation resulted in an increase in hearing thresholds across all frequencies examined (2 – 32 kHz). In all groups, after initial loss, auditory thresholds improved after the first week and stabilised by 4 weeks and remained stable until the end of the trial period. No mean progressive loss was evident in this experimental model beyond 4 weeks. Thresholds were less elevated after dexamethasone treatment with maximal protection occurring at 32 kHz. Much greater protection was achieved when dexamethasone was applied for longer period even at a lower loading dose. Higher concentration of dexamethasone applied for shorter duration resulted in protection over basal frequencies but no significant protection was afforded to more apical regions of cochlea. CONCLUSION: A single dose of steroid may be applied to cochlear round window to achieve protection of residual hearing against implantation related trauma, using a locally applied delivery vehicle such as a bio-degradable bead. Protection is both immediate and long-term. This effect occurs in a manner dependent upon an interplay between the loading dosage and the duration of the application, with the latter likely to be more important variable than the size of the dosing in achieving more potent and broader frequency protection. However, the requirement for such lengthy duration of treatment poses practical challenges for the clinical translation of this experiment.