title: Profound hearing loss in the cat following the single co-administration of kanamycin and ethacrynic acid.
abstract: Co-administration of kanamycin (KA) with the loop diuretic ethacrynic acid (EA) has previously been shown to produce a rapid and profound hearing loss in guinea pigs. In the present study we describe a modified technique for developing a profound hearing loss in cats. By monitoring the animal's hearing status during the intravenous infusion of EA the technique minimizes the effects of individual variability to the drug regime. Seven cats received a subcutaneous injection of KA (300 mg/kg) followed by intravenous infusion of EA (1 mg/min). Click-evoked auditory brainstem responses (ABRs) were recorded to monitor the animal's hearing during the infusion. When the ABR thresholds rose rapidly to levels in excess of 90 dB SPL the infusion of EA was stopped. This occurred at EA doses of 10-25 mg/kg, indicating considerable individual variability to the deafening procedure. However, there was a strong negative correlation (r = -0.93) between the EA dose and body weight which accounted for much of this variability. Subsequent ABR monitoring showed that this profound hearing loss was both bilateral and permanent. Significantly, blood urea and creatinine levels, monitored for periods of up to three days after the procedure, remained within the normal range. Furthermore, there was no clinical evidence of renal dysfunction as indicated by weight loss or oliguria. Cochlear histopathology, examined after a two months to three year survival period, showed an absence of all inner and outer hair cells in the majority of cochleas. The extent of loss of spiral ganglion cells was dependent on their distance from the round window and the period of survival following the deafening procedure. Clearly, the degeneration of spiral ganglion cells continued for several years following the initial insult. Finally, we observed no evidence of renal histopathology. In conclusion, the co-administration of KA and EA produces a profound hearing loss in cats without evidence of renal impairment. Monitoring the animal's hearing status during the procedure ensures that the dose of EA can be optimised for individual animals. Moreover, it may be possible to adapt this procedure to produce animal models with controlled high frequency hearing losses.
authors.affiliation: Department of Otolaryngology, University of Melbourne, Parkville, Victoria, Australia.
authors.forename: S A
authors.initials: SA
authors.lastname: Xu
authors.forename: R K
authors.initials: RK
authors.lastname: Shepherd
authors.forename: Y
authors.initials: Y
authors.lastname: Chen
authors.forename: G M
authors.initials: GM
authors.lastname: Clark
mesh_terms: D000818:Animals; D002415:Cats; D003051:Cochlea / Q000473:pathology*; D003638:Deafness / Q000139:chemically induced / Q000473:pathology; D003712:Dendrites / Q000187:drug effects / Q000473:pathology; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004976:Ethacrynic Acid / Q000633:toxicity*; D016057:Evoked Potentials, Auditory, Brain Stem / Q000187:drug effects*; D006198:Hair Cells, Auditory / Q000187:drug effects / Q000473:pathology; D007612:Kanamycin / Q000633:toxicity*; D007668:Kidney / Q000187:drug effects / Q000502:physiology; D009925:Organ of Corti / Q000187:drug effects / Q000473:pathology; D013136:Spiral Ganglion / Q000166:cytology / Q000187:drug effects / Q000473:pathology
chemical_list: D007612:Kanamycin; D004976:Ethacrynic Acid