COCHLEAR FUNCTION AFTER SELECTIVE INNER HAIR CELL DEGENERATION INDUCED BY CARBOPLATIN

The ototoxicity of carboplatin, a second generation anti-cancer agent, was examined using the chinchilla as an animal model. In animals trea ted with a clinical therapeutic dose (400 mg/m(2)), the dominant degen erative change is to inner hair cells (IHCs). This is in sharp contras t to most other ototoxic agents, which damage primarily the outer hair cells (OHCs). Functional changes to the cochlea have been evaluated i n carboplatin treated subjects by recording cochlear action potentials (CAP) and cochlear microphonics (CM); cochlear lesions were evaluated using scanning electron microscopy. In carboplatin treated animals, C AP thresholds to tone-pip stimuli were elevated in proportion to IHC d amage in corresponding cochlear regions. In contrast, CM amplitudes an d 'thresholds' remained close to normal in most cases, reflecting the preservation of OHCs in the basal turn. These results indicate a high degree of independence between the inner and outer hair cell systems i n the cochlear transduction mechanism. We suggest that this species-sp ecific preparation with selective IHC loss will provide a valuable too l for studying, separately, the role of OHCs in both afferent and effe rent cochlear function.