Perilymphatic application of cisplatin over several days in albino guinea pigs: dose-dependency of electrophysiological and morphological effects

Cisplatin, at 0, 3, 30 or 300 mug/ml in saline, was applied to the scala ty mpani of the cochlea of guinea pigs via osmotic mini-pumps, operating at a pump rate of 0.5 mul/h. Electrocochleographic recordings were made from an implanted round window electrode. When an electrocochleographic criterion o f ototoxicity was reached (40 dB loss in compound action potential (CAP) th reshold at 8 kHz), or after 1 week if this criterion was not reached, the a nimals were sacrificed for light microscopy. A subgroup of animals had endo cochlear potentials (EPs) measured prior to sacrifice. Hearing remained sta ble in the 0 mug/ml control group, but a sudden drop of auditory sensitivit y across the whole frequency range was observed in all other groups. It too k 15 days before the drop occurred, dependent on cisplatin concentration. C AP and cochlear microphonics were lost simultaneously. The EP was severely depressed in the affected animals, suggesting that cisplatin effects on the EP are primary. However. histology revealed an accompanying loss of outer hair cells, primarily in the basal turn. It is concluded that if cisplatin is given until ototoxicity becomes apparent electrophysiologically, then th e cochlear pathology from intrascalar cisplatin administration resembles th at from daily parenteral administration at 1.5-2.0 mg/kg. The cochlear path ology from the parenteral treatment was greater than that observed with 30 mug/ml pumps, and less than that From 300 mug/ml pumps. (C) 2001 Elsevier S cience B.V. All rights reserved.