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Gentamicin Applied to the Oval Window Suppresses Vestibular Function in Guinea Pigs

Journal of the Association for Research in Otolaryngology volume 18, pages 291–299 (2017)Cite this article

Abstract

Intratympanic gentamicin therapy is widely used clinically to treat the debilitating symptoms of Ménière’s disease. Cochleotoxicity is an undesirable potential side effect of the treatment and the risk of hearing loss increases proportionately with gentamicin concentration in the cochlea. It has recently been shown that gentamicin is readily absorbed through the oval window in guinea pigs. The present study uses quantitative functional measures of vestibular and cochlea function to investigate the efficacy of treating the vestibule by applying a small volume of gentamicin onto the stapes footplate in guinea pigs. Vestibular and cochlea function were assessed by recording short latency vestibular evoked potentials in response to linear head acceleration and changes in hearing threshold, respectively, 1 and 2 weeks following treatment. Histopathology was analyzed in the crista ampullaris of the posterior semi-circular canal and utricular macula in the vestibule, and in the basal and second turns of the cochlea. In animals receiving gentamicin on the stapes footplate, vestibular responses were significantly suppressed by 72.7 % 2 weeks after treatment with no significant loss of hearing. This suggests that the vestibule can be treated directly by applying gentamicin onto the stapes footplate.

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References

  • Aran JM, Chappert C, Dulon D, Erre JP, Aurousseau C (1995) Uptake of amikacin by hair cells of the guinea pig cochlea and vestibule and ototoxicity: comparison with gentamicin. Hear Res 82:179–183

    CAS  Article  PubMed  Google Scholar 

  • Becvarovski Z, Bojrab DI, Michaelides EM et al (2002) Round window gentamicin absorption: an in vivo human model. Laryngoscope 112(9):1610–1613

    CAS  Article  PubMed  Google Scholar 

  • Bohmer A (1995) Short latency vestibular evoked responses to linear acceleration stimuli in small mammals: masking effects and experimental applications. Acta Otolaryngol Suppl 520(Pt1):120–123

    Article  PubMed  Google Scholar 

  • Bohmer A, Hoffman LF, Honrubia V (1995) Characterization of vestibular potentials evoked by linear acceleration pulses in the chinchilla. Am J Otol 16:498–504

    CAS  PubMed  Google Scholar 

  • Bremer GH, de Groot JC, Versnal H, Klis SF (2012) Combined administration of kanalycin and furosemide does not result in loss of vestibular function in Guinea pigs. Audiol Neurootol 17:25–38

    CAS  Article  PubMed  Google Scholar 

  • Carey J (2004) Intratympanic gentamicin for the treatment of Meniere’s disease and other forms of peripheral vertigo. Otolaryngol Clin N Am 37:1075–1090

    Article  Google Scholar 

  • Chia SH, Garnst AC, Anderson JP, Harris JP (2004) Intratympanic gentamicin therapy for Mèniére’s disease: a meta analysis. Otol Neurotol 25:544–552

    Article  PubMed  Google Scholar 

  • Chihara Y, Wang V, Brown DJ (2013) Evidence for the utricular origin of the vestibular short-latency-evoked potential (VsEP) to bone-conducted vibration in guinea pig. Exp Brain Res 229(2):157–170

    Article  PubMed  Google Scholar 

  • Diamond C, O’Connell DA, Hornig JD et al (2003) Systematic review of intratympanic gentamicin in Meniere’s disease. J Otolaryngol 32(6):351–361

    Article  PubMed  Google Scholar 

  • Floc’h JL et al (2014) Markers of cochlear inflammation using MRI. J Magn Reson Imaging 39(1):150–161

    Article  PubMed  Google Scholar 

  • Goycoolea MV (2001) Clinical aspects of round window membrane permeability under normal and pathological conditions. Acta Otolaryngol 121(4):437–447

    CAS  Article  PubMed  Google Scholar 

  • Hirose K et al (2014) Systemic lipopolysaccharide compromises the blood-labyrinth barrier and increases entry of serum fluorescein into the perilymph. J Assoc Res Otolaryngol 15(5):707–719

    Article  PubMed  PubMed Central  Google Scholar 

  • King EB, Salt AN, Eastwood HT, O’Leary SJ (2011) Direct entry of gadolinium into the vestibule following intratympanic applications in Guinea pigs and the influence of cochlear implantation. JARO 12(6):741–751

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  • King EB, Salt AN, Kel GE, Eastwood HT, O’Leary SJ (2013) Gentamicin administration on the stapes footplate causes greater hearing loss and vestibulotoxicity than round window administration in guinea pigs. Hear Res 304:159–166

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  • Kingma CM, Wit HP (2010) The effect of changes in perilymphatic K+ on the vestibular evoked potential in the guinea pig. Eur Arch Otorhinolaryngol 267:1679–1684

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  • Kujawa SG, Liberman MC (2009) Adding insult to injury: cochlear nerve degeneration after “temporary” noise-induced hearing loss. J Neuroscience 29:14077–14085

    CAS  Article  PubMed  Google Scholar 

  • Lange G (1989) Gentamicin and other ototoxic antibiotics for the transtympanic treatment of Menière’s disease. Arch Otorhinolaryngol 246(5):269–270

    CAS  Article  PubMed  Google Scholar 

  • Lindeman H (1969) "Regional differences in structure of the vestibular sensory regions." The Journal of Laryngology & Otology 83.01: 1-17

  • McCall AA, Leary Swan EE, Borenstein JT, Sewell WF, Kujawa SG, McKenna MJ (2010) Drug delivery for treatment of inner ear disease: current state of knowledge. Ear & Hearing 31:156–165

    Article  Google Scholar 

  • Merchant SN (1999) A method for quantitative assessment of vestibular otopathology. Laryngoscope 109:1560–1569

    CAS  Article  PubMed  Google Scholar 

  • Merchant SN, Nadol JB (2010) Schuknecht’s Pathology of the Ear, People’s Medical Publishing House USA, 3rd Edition

  • Nadol JB (1977) Positive Hennebert’s sign in Ménierè’s disease. Arch Otolaryngol 103:524–530

    Article  PubMed  Google Scholar 

  • Nakashima T, Teranishi M, Hibi T, Kobayashi M, Umemura M (2000) Vestibular and cochlear toxicity of aminoglycosides: a review. Acta Otolaryngol 120:904–911

    CAS  Article  PubMed  Google Scholar 

  • Oei MLYM, Segenhout JM, Wit HP, Albers FW (2001) The vestibular evoked response to linear, alternating, acceleration pulses without acoustic masking as a parameter of vestibular function. Acta Otolaryngol 121:62–67

    CAS  Article  PubMed  Google Scholar 

  • Plontke SKR, Wood AWW, Salt AN (2002) Analysis of gentamicin kinetics in fluids of the inner ear with round window administration. Otol Neurotol 23:67–974

    Article  Google Scholar 

  • Quaranta A, Aloisi A, De Benedittis G, Scaringi A (1999) Intratympanic therapy for Ménière’s disease. High-concentration gentamicin with round-window protection. Ann N Y Acad Sci 884:410–424

    CAS  Article  PubMed  Google Scholar 

  • Salt AN, Gill RM, Plontke SK (2008) Dependence of hearing changes on the dose of intratympanically applied gentamicin: a meta-analysis using mathematical simulations of clinical drug delivery protocols. Laryngoscope 118:1793–1800

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  • Schuknecht HF (1993) Pathology of the ear, 2nd edn. Lea & Febiger, Philadelphia/Baltimore

    Google Scholar 

  • Shi H, Li Y, Yin S, Zou J (2014) The predominant vestibular uptake of gadolinium through the oval window pathway is compromised by endolymphatic hydrops in Ménière’s disease. Otol Neurotol 35(2):315–322

    Article  PubMed  Google Scholar 

  • Smith BM, Myers MG (1979) The penetration of gentamicin and neomycinin to perilymph across the round window membrane. Otolaryngol Head Neck Surg 87(6):888–891

    CAS  Article  PubMed  Google Scholar 

  • Tanaka K, Motomura S (1981) Permeability of the labyrinthine window in guinea pigs. Arch Otorhinolarygnol 233:67–73

    CAS  Article  Google Scholar 

  • Wackym PA, Schuknecht HF, Ward PH, Linthicum FH, Kerner MM, Aframian D et al (1994) Blinded control study of endolymphatic duct and sac fibrosis in Meniere’s disease. In: Filipo R, Barbara M (eds) Meniere’s disease: perspectives in the 90s. Kugler Publishing, Amsterdam/New York, pp. 209–215

    Google Scholar 

  • Zou J, Pyykkö I, Bjelke B, Dastidar P, Toppila E (2005) Communication between the perilymphatic scalae and spiral ligament visualized by in vivo MRI. Audiol Neurotol 10:145–152

    Article  Google Scholar 

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Acknowledgements

This study was funded by the Garnett Passe & Rodney Williams Memorial Foundation. This authors wish to thank Mr. Rodney Millard, Mr. Mark Harrison, and Dr. Mohit Shivdasani from the Bionics Institute and Professor Ian Curthoys from the University of Sydney for their input into setting up the VsEP recording equipment at the Bionics Institute; Professor Alec Salt from Washington University School of Medicine, St Louis, USA, for technical advice; Ms. Shefin George from the Bionics Institute for her assistance with perfusions; and Miss Prudence Neilson from University of Melbourne for preparing histology slides. The time invested by A/Prof Fallon, Prof Shepherd, Dr. Brown were supported by research grants from the NHMRC (GNT1081478) and the Garnett Passe and Rodney Williams Memorial Foundation.

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Authors and Affiliations

  1. Bionics Institute of Australia, 384-388 Albert Street, East Melbourne, VIC, 3002, Australia

    E. B. King, R. K. Shepherd & J. B. Fallon

  2. Medical Bionics Department, University of Melbourne, Melbourne, VIC, Australia

    R. K. Shepherd & J. B. Fallon

  3. The Brain and Mind Research Institute, Sydney Medical School, The University of Sydney, Sydney, NSW, Australia

    D. J. Brown

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  1. E. B. King
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  2. R. K. Shepherd
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  3. D. J. Brown
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  4. J. B. Fallon
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Correspondence to J. B. Fallon.

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King, E.B., Shepherd, R.K., Brown, D.J. et al. Gentamicin Applied to the Oval Window Suppresses Vestibular Function in Guinea Pigs. JARO 18, 291–299 (2017). https://doi.org/10.1007/s10162-016-0609-1

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  • DOI: https://doi.org/10.1007/s10162-016-0609-1

Keywords

  • Gentamicin
  • Aminoglycoside
  • Vestibulotoxicity
  • Ototoxicity
  • Oval window
  • Stapes
  • Stapediovestibular joint
  • Annular ligament
  • Intratympanic
  • Pharmacokinetics