Onset of ototoxicity in the cat is related to onset of auditory function

Abstract

Cats are altricial mammals; they are born deaf and undergo rapid maturation of the auditory periphery late in the first and throughout the 2nd week of life. Previous studies, using multiple aminoglycoside administration over several days or weeks, have indicated that there is a reduction in the degree of ototoxicity in young animals provided the drug is administered prior to the onset of auditory function. In order to provide a more precise relationship between the degree of ototoxicity and auditory development, we used a single administration of Kanamycin (KA) and the loop diuretic ethacrynic acid (EA), as the co-administration of these drugs is known to produce a rapid and profound hearing loss in adult animals. Thirty kittens were administered with KA and EA at ages that varied from 2 to 16 days after birth (DAB) using a fixed dose per kilogram body weight sufficient to profoundly deafen adult animals. All animals made an unevenful recovery from the procedure. At 26 DAB, tone-pip-evoked auditory brainstem responses (ABR) were recorded from each animal in order to establish the extent of the hearing loss. The degree of hearing loss was compared with normal ABR audiograms recorded from 6 age-matched control animals. All animals treated with KA/EA at 9 DAB or older had a profound hearing loss similar to adult animals. Animals treated between 2 and 8 DAB exhibited severe high-frequency hearing losses. The extent of the loss was correlated with age ( r = 0.63) and body weight ( r = 0.72) such that hearing loss tended to spread towards lower frequencies as age and/or weight increased. All animals exhibited bilaterally symmetrical hearing losses which remained relatively stable over monitoring periods of up to 6 months following the drug treatment. These findings imply that the onset of ototoxicity is related, at least in part, to the onset of auditory function in the kitten. The rapid onset of deafness following this procedure makes it a useful technique in the study of both ototoxicity and cochlear development.