A Guinea Pig Model of Selective Severe High-Frequency Hearing Loss

Hypothesis: Using an appropriate dose of an aminoglycoside antibiotic cotreated with a loop diuretic a guinea pig model of high-frequency loss can be obtained mimicking cochlear implant candidates with low-frequency residual hearing. We examined the stability of this model over time. Background: A well-established method to create an animal model for profound deafness is cotreatment with an aminoglycoside antibiotic and a loop diuretic. Recent data indicated that reduction of the aminoglycoside dose might yield selective high-frequency hearing loss. Such a model is relevant for studies related to hybrid cochlear implant devices, for example, with respect to preservation of residual hearing. Methods: Guinea pigs received an electrode for chronic recording of compound action potentials to tones to assess thresholds. They were treated with a coadministration of kanamycin (200 mg/kg) and furosemide (100 mg/kg), after which, the animals were sacrificed for histologic analysis at 2, 4, or 7 weeks. Results: After 2 to 7 weeks threshold shifts were greater than 50 dB for 8 to 16 kHz in 15 of 17 animals, whereas threshold shifts at 2 kHz or lower were less than 50 dB in 13 animals. Major threshold shifts occurred the first 2 to 4 days; subsequently, some spontaneous recovery occurred and, after 2-3 weeks thresholds, remained stable. Inner hair cell loss still progressed between 2 and 4 weeks in the most basal cochlear region; thereafter, hair cell loss was stable. Conclusion: An appropriate animal model for selective severe high-frequency hearing loss was obtained, which is stable at 4 weeks after ototoxic treatment.