Inner ear effects of exogenous hyaluronan in the middle ear of the rat.

1.9% hyaluronan (HA) (mol. wt. 3 x 10(6] was applied repeatedly into the middle ear of rats through a myringotomy. The function and structure of the cochlea was analysed by auditory brainstem recordings (ABR) at 2-31.5 kHz and by light microscopy. The myringotomy significantly impaired the ABR thresholds at frequencies below 8 kHz. Five days after the last application of HA, the ABR thresholds showed minor improvements at 6-8 kHz but were impaired at 12 and 20 kHz, as compared with control levels. One month after the last administration of HA, ABR thresholds were significantly improved as compared with the initial level at 2-6 kHz but normal at all other frequencies. After 3 months, all ABR thresholds had returned to the pre-treatment (normal) level. Five days after the last application of HA, the latencies for almost all frequencies were significantly prolonged for waves II and IV at the ABR threshold. After 3 months all latencies had returned to their pre-treatment (normal) values. Highly concentrated hyaluronan (1.9%) is free from ototoxicity but does have transient functional effects on the inner ear.