Pharmacological protection of auditory function against noise and hypoxia with MK 801
INTRODUCTION: Pharmacological protection of cochlear function is one of the most exciting goals of inner ear medicine. The selective glutamate antagonist MK 801 may be neuro-protective to the cochlea.1 This study aims to investigate whether round window administration of MK 801 protects cochlear function against a combination of noise and atmostpheric hypoxia. METHODS: Eight guinea-pigs were studied. Round Window E. Catheters (Durect Inc., USA) were implanted through a trans-bulla approach and EcoG thresholds determined at 8, 16, 24 and 30 kHz. Artificial perilymph (n = 4) or 10 mM MK 801 (n = 4) was then perfused onto the round window membrane. After 15 min the anaesthetized animals were exposed to 100 dB white noise in 11.5-12. 5% atmospheric oxygen. Thresholds were determined before and 15 min after exposure. RESULTS: The mean threshold shifts from pre-perfusion at 8, 16, 24 and 30 kHz were 40, 33, 35 and 17 dB, respectively (in control animals) and 29, 28, 33 and 41 dB, respectively (in treated animals). A marginal protective effect was demonstrated at 8 kHz (P = 0.06). The 30-kHz thresholds in the treated group fell by 61 dB before noise exposure compared to < 1 dB in the controls (P = 0.0007), suggesting that at high frequencies, 10 mM MK 801 may itself be ototoxic. CONCLUSIONS: These results partially support existing data suggesting that pharmacological protection against noise/hypoxia is possible. Administration of round window NMDA antagonists may affect normal auditory threshold making detailed evaluation of the toxicity of potential inner ear therapies essential before clinical use is contemplated.
Selvadurai
DK
Department of ENT Surgery, Leicester Royal Infirmary, Leicester, Medicine Evaluation and Applied Technology Group, Glaxco-Wellcome and MRC Centre for Toxicology, Leicester University, Leicester, UK).
Etheridge
S
Jones
P
Mulheran
M
Cook
JA