BLOOD FLOW-INDEPENDENT ACCUMULATION OF CISPLATIN IN THE GUINEA-PIG COCHLEA

Considerable interindividual variability in the ototoxic effect of cis platin has become the unpredictable dose-limiting factor in its use as curative as well as palliative therapy. The drug accumulates in highl y vascular areas in the cochlea, causing dose-related hair cell loss. The purpose of this study was to assess blood how-dependent aspects of cisplatin absorption in the cochlea in order to better understand fac tors that may influence cisplatin-induced ototoxicity. The effect of r educed cochlear blood flow on the ototoxic action of cisplatin was stu died in guinea pigs. Before cisplatin administration the cochlear vasc ulature in each animal was unilaterally pre-constricted, by the applic ation of 2% epinephrine to the round window. A 20-30% reduction in coc hlear blood flow, assessed by laser Doppler flowmetry, was maintained before and after intravenous infusion of 0.1% cisplatin. Cisplatin inf usion affected cochlear blood flow but not vessel conductivity. The co chlear blood how decrease, maintained by local epinephrine application to the round window during cisplatin infusion, did not alter the cisp latin-induced hearing loss. In addition, the concentration of free cis platin in scala tympani perilymph did not differ between epinephrine-t reated and non-treated ears. Our results indicate that cisplatin trans port into the cochlea is not an energy-dependent process in the latera l wall vasculature.