Reversible Changes in Inner Ear Function Following Hyaluronan Application in the Middle Ear

Abstract

A safety study regarding the potential ototoxicity of 1.9% hyaluronan was performed in 20 rats. In all animals the middle ear was completely filled with hyaluronan three times at 2-day intervals between the administrations. Inner ear function was evaluated by computerized auditory brainstem response (ABR) measurements. ABR recordings were performed prior to exposure, after myringotomy (but prior to administration of hyaluronan), 5 days after the last administration (n = 15; these animals were then sacrificed for analysis of the middle ear), one month and 3 months later (n =5). The hearing thresholds were improved in animals 5 days after the last administration of hyaluronan at 6–8 kHz, whereas the hearing thresholds were impaired at 12 and 20 kHz. After one month, ABR thresholds were even better than precontrol levels at 2, 4 and 6 kHz, whereas at all other frequencies the ABR threshold was normal. Three months after hyaluronan exposure, all ABR thresholds were normal, but viscous material was present in the middle ear in 3 of 5 animals. It is concluded that hyaluronan causes revesible changes in inner ear function but lacks ototoxic adverse effects.

Key Words:

• hyaluronan
• middle ear
• inner ear
• ototoxicity
• hearing threshold
• function