PROFOUND HEARING-LOSS IN THE CAT FOLLOWING THE SINGLE COADMINISTRATION OF KANAMYCIN AND ETHACRYNIC-ACID

Co-administration of kanamycin (KA) with the loop diuretic ethacrynic acid (EA) has previously been shown to produce a rapid and profound he aring loss in guinea pigs. In the present study we describe a modified technique for developing a profound hearing loss in cats. By monitori ng the animal's hearing status during the intravenous infusion of EA t he technique minimizes the effects of individual variability to the dr ug regime. Seven cats received a subcutaneous injection of KA (300 mg/ kg) followed by intravenous infusion of EA (1 mg/min). Click-evoked au ditory 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 oc curred at EA doses of 10-25 mg/kg, indicating considerable individual variability to the deafening procedure. However, there was a strong ne gative correlation (r = -0.93) between the EA dose and body weight whi ch accounted for much of this variability. Subsequent ABR monitoring s howed that this profound hearing loss was both bilateral and permanent . Significantly, blood urea and creatinine levels, monitored for perio ds of up to three days after the procedure, remained within the normal range. Furthermore, there was no clinical evidence of renal dysfuncti on as indicated by weight loss or oliguria. Cochlear histopathology, e xamined after a two months to three year survival period, showed an ab sence of all inner and outer hair cells in the majority of cochleas. T he extent of loss of spiral ganglion cells was dependent on their dist ance from the round window and the period of survival following the de afening 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-ad ministration of KA and EA produces a profound hearing loss in cats wit hout evidence of renal impairment. Monitoring the animal's hearing sta tus during the procedure ensures that the dose of EA can be optimised for individual animals. Moreover, it may be possible to adapt this pro cedure to produce animal models with controlled high frequency hearing losses.