title: Effects of a dexamethasone-releasing implant on cochleae: A functional, morphological and pharmacokinetic study.
abstract: OBJECTIVE
  This study evaluated the impact of a dexamethasone-releasing silicone implant on hearing function preservation, cochlear morphology and perilymph pharmacokinetics after cochlear implantation.
  
  
  METHODS
  Guinea pigs were implanted unilaterally with silicone rods containing either 2% dexamethasone (DEXA group, n = 18) or no dexamethasone (control group, n = 17). Auditory brainstem response (ABR) and distortion product otoacoustic emissions (DPOAEs) were measured preoperatively and over 6 months postoperatively. Cochlear histology using standard hematoxylin and eosin (H&E) staining and tumor necrosis factor (TNF)-alpha staining was performed 1 month postoperatively. Twenty-two guinea pigs were involved in the pharmacokinetic study, and real-time drug concentrations in perilymph were investigated using high-performance liquid chromatography (HPLC). The Mann-Whitney U test (1-tailed) was used for statistical analyses.
  
  
  RESULTS
  ABR and DPOAE testing demonstrated decreased hearing function immediately postoperatively followed by a progressive hearing loss within the first day postoperatively. There was almost no observable hearing improvement in the control group from 1 week to 6 months postoperatively, but hearing levels in the DEXA group improved gradually from 1 week to 12 weeks. Hearing loss in the DEXA and control group was 5.0 ± 3.4 dB and 21.7 ± 5.3 dB, respectively at a 16-kHz stimulus frequency 6 months postoperatively. The difference in threshold shifts was present throughout all measured frequencies, and it was significant at 4-24 kHz. The morphological study revealed new fibrosis formation in the scala tympani, which encapsulated the implanted electrode. TNF-alpha positive staining in the cochleae of the DEXA group was less evident than the control group. The pharmacokinetic study revealed a peak perilymph concentration 30 min postoperatively and sustained dexamethasone release at least 1 week postoperatively.
  
  
  CONCLUSIONS
  Cochlear implants that incorporate dexamethasone can release drug chronically in the inner ear and induce significant long-term recovery and preservation of auditory function after implantation.
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Beijing Naval General Hospital, Beijing 100048, PR China.
authors.forename: Ya
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Electrode Research Section, MED-EL Medical Electronics, Innsbruck, Austria.
authors.forename: Claude
authors.initials: C
authors.lastname: Jolly
authors.affiliation: MED-EL Deutschland GmbH, Starnberg, Germany.
authors.forename: Susanne
authors.initials: S
authors.lastname: Braun
authors.affiliation: Clinic for Otorhinolaryngology, Head- and Neck Surgery, Klinikum rechts der Isar, Technical University of Munich, Munich, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Janssen
authors.affiliation: Clinic for Otorhinolaryngology, Head- and Neck Surgery, Klinikum rechts der Isar, Technical University of Munich, Munich, Germany.
authors.forename: Elias
authors.initials: E
authors.lastname: Scherer
authors.affiliation: Clinic for Otorhinolaryngology, Head- and Neck Surgery, Klinikum rechts der Isar, Technical University of Munich, Munich, Germany.
authors.forename: Jochen
authors.initials: J
authors.lastname: Steinhoff
authors.affiliation: Clinic for Otorhinolaryngology, Head- and Neck Surgery, Klinikum rechts der Isar, Technical University of Munich, Munich, Germany.
authors.forename: Harald
authors.initials: H
authors.lastname: Ebenhoch
authors.affiliation: Clinic for Otorhinolaryngology, Head- and Neck Surgery, Klinikum rechts der Isar, Technical University of Munich, Munich, Germany.
authors.forename: Andrea
authors.initials: A
authors.lastname: Lohner
authors.affiliation: Clinic for Otorhinolaryngology, Head- and Neck Surgery, Klinikum rechts der Isar, Technical University of Munich, Munich, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Stark
authors.affiliation: HNO-Zentrum Neupfarrplatz, 12/II, 93047 Regensburg, Germany. Electronic address: Jn.Kiefer@googlemail.com.
authors.forename: Jan
authors.initials: J
authors.lastname: Kiefer
mesh_terms: D000161:Acoustic Stimulation; D000818:Animals; D001309:Auditory Threshold / Q000187:drug effects; D002851:Chromatography, High Pressure Liquid; D003051:Cochlea / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D003054:Cochlear Implants; D003907:Dexamethasone / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D004195:Disease Models, Animal; D004343:Drug Implants; D016057:Evoked Potentials, Auditory, Brain Stem / Q000187:drug effects; D005355:Fibrosis; D005938:Glucocorticoids / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D006168:Guinea Pigs; D006309:Hearing / Q000187:drug effects*; D034381:Hearing Loss / Q000175:diagnosis / Q000209:etiology / Q000378:metabolism / Q000503:physiopathology / Q000517:prevention & control*; D017084:Otoacoustic Emissions, Spontaneous / Q000187:drug effects; D010498:Perilymph / Q000378:metabolism; D012828:Silicones / Q000737:chemistry; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D004343:Drug Implants; D005938:Glucocorticoids; D012828:Silicones; D014409:Tumor Necrosis Factor-alpha; D003907:Dexamethasone