Quantitative relationship of carboplatin dose to magnitude of inner and outer hair cell loss and the reduction in distortion product otoacoustic emission amplitude in chinchillas

Abstract

The outer hair cells (OHCs) are thought to be the dominant source of distortion product otoacoustic emissions (DPOAEs) in the mammalian cochlea; however, little is known about the quantitative relationship between reduction in DPOAE amplitude and the degree of inner hair cell (IHC) and OHC loss. To examine this relationship, we measured the DPOAE input/output functions in the chinchilla before and after destroying the IHCs and/or OHCs with carboplatin. Low-to-moderate doses (38-150 mg/kg, i.p.) of carboplatin selectively destroyed some or all of the IHCs along the entire length of the cochlea while sparing the OHCs. Selective loss of all the IHCs had little effect on DPOAE amplitude as long as the OHCs were present. With high doses of carboplatin (200 mg/kg, i.p.), there was complete destruction of IHCs plus massive OHC loss that decreased from the base towards the apex of the cochlea. OHC loss resulted in a large decrease in DPOAE amplitude. DPOAE amplitude at 9.6 kHz decreased at the rate of 4.1 dB for every 10% loss of OHCs. At 7.2 and 4.8 kHz, DPOAE amplitude decreased 3.1 dB and 2.4 dB per 10% OHC loss, respectively. These results indicate that OHCs are the dominant source of DPOAEs.