An Experimental Study on the Progressiveness of Cochlear Damage by Aminoglycoside Drug

Abstract

The administration of the aminoglycoside antibiotics often gives rise to sensori-neural hearing loss. in a study undertaken to explore the progression of hearing loss caused by these drugs, guinea pigs were administered with kanamycin, a representative member of this family of antibiotics, and subsequently were investigated for the presence or absence of hearing loss and its progressive-ness during and after the period of medication in terms of audiogenic brain stem response (BSR). Further, in an attempt to investigate the relationship between the function and morphology of a KM-damaged inner ear, light microscopic as well as scanning and transmission electron microscopic examinations were made of the cochleas excised from the treated animals. the results are summarized as follows

(1) Four distinct wave forms, i.e., P₁, P₂, P₃ and P₄, were seen in BSR tracings from normal guinea pigs.

(2) a comparative study was made of BSR amplitude as an index of hearing. in the group receiving KM in consecutive daily doses of 500 mg/kg, the amplitude of BSR, after showing a transient increase around the 7th day of medication, decreased rapidly to zero thereafter. It became thus obvious that hearing is kept normal over a certain period of time after the initiation of KM administration and becomes quickly impaired once past this critical point of time.

(3) a major morphological correlate of a failure of the organ of Corti to respond to phonic stimuli was severe destruction and disappearance of the outer hair cells. Fragments of degenerated outer hair cells were seen to be scattered on the reticular membrane on electron microscopy.

(4) in some instances KM medication, at 400 mg/kg daily, was discontinued before an appreciable change occurred in the BSR pattern but, nevertheless, the amplitude of BSR was reduced to zero on the 9th day after withdrawal of the drug. at that time pronounced degenerative changes in and disappearance of the outer hair cells were noted in the organ of Corti. These findings, though varied to a considerable extent with different individuals, suggest the likelihood that KM therapy gives rise to hearing loss even when it is discontinued before its ototoxic effect becomes manifest.

1) in den Hirnstammpotentialen von den normalen Meerschweinchen waren namentlich P₁-, P₂-, P₃- und P₄-Wellen bemerkbar.

2) in den mit 500 mg/kg von Kanamycin täglich be-handelten Tieren nahm die Amplitude der Potentiale gegen den siebenten Tag vorübergehend zu, um danach schnell abzunehmen und zu verschwinden. Es soil be-deuten, daβ das Gehörvermögen während einer bestimmten Zeit der Behandlung mit Kanamycin erhalten bleibt, doch danach schnell verlorengeht.

3) Zu der Zeit, wo sie auf den Gehörstimuli nicht mehr reagierten, waren besonders die äuβeren Haarzellen des Cortischen Organs in hohem Grade zerstört oder verschwunden, so dβ sich degenerierte äuβere Haarzellen vereinzelt auf der reticulären Membran befanden.

4) Wenn auch man die Behandlung (mit 400 mg/kg von Kanamycin fünfmal täglich) vor dem Eintritt der veränderten Potentiale unterbrach, konnte man infolgedessen die fast null gewordene Amplitude und die in hohem Grade entarteten äuβeren Haarzellen des Cortischen Organs in mehreren Fällen konstatieren, obwohl es individuelle Unterschiede gab. Demgemäβ soil es möglich sein, daβ trotz der Unterbrechung der Behandlung vor dem Eintritt des veränderten Gehörvermögens, sich zuweilen Schwerhörigkeit ereignet.