Objective - The round window membrane (RWM) is known to be permeable to various biological substances. Application of biological substances to the RWM has been shown to affect inner ear fluid composition and damage hair cells, resulting in functional changes. RWM instillation of gentamicin, a preferentially vestibulotoxic aminoglycoside, is used as a therapeutic treatment for patients with intractable vertigo and is gaining acceptance as a chemical vestibular ablation agent, despite considerable variations in the incidence and severity of hearing loss associated with gentamicin. Clearly, the susceptibility of vestibular and auditory hair cells to the ototoxic effects of gentamicin is not well understood. The aim of this study was to understand the kinetics of urea and methylene blue instilled into the inner ear space through the RWM and to establish a method for determining the optimal dosage for the treatment of inner ear disorders. Material and Methods - We used inner ear microdialysis to quantify changes in perilymph concentration of low molecular weight agents applied to the RWM in a chinchilla model. Results - Preliminary results after placement of a microdialysis probe and application of a low molecular weight marker (urea) to the RWM were extrapolated from a time versus concentration plot from dialysates sampled over a 3-min interval using modifications of standard microdialysis equations for estimation of in vivo recovery. Our data suggest that inner ear microdialysis can be used to measure the pharmacokinetics of a low molecular weight agent within the perilymphatic space without the need for repeated direct sampling. Conclusion - Inner ear microdialysis may be a useful method for establishing a therapeutic dosage for ototoxic agents used in the treatment of inner ear disorders.
Bibliographical noteFunding Information:
We thank Dr Alec Salt for reviewing this manuscript and for the generous contribution of his modeling software used to evaluate the dynamics of inner-ear fluid movement in our microdialysis method. Funding for this research was provided by the Minnesota Medical Foundation and the Lions 5M Hearing Foundation.
- Hair cells
- Inner ear disease