Combined Administration of Kanamycin and Furosemide Does Not Result in Loss of Vestibular Function in Guinea Pigs

Abstract

Aminoglycoside antibiotics are known to damage the vestibular and auditory sensory epithelia. Although loop diuretics enhance the cochleotoxic effect of aminoglycosides, it is not known whether concomitant administration of an aminoglycoside and a loop diuretic affects the vestibular system. The aim of our study was to investigate the effect of co-administration of kanamycin and furosemide upon the otolith organs and to compare it to the known vestibulotoxic effect of gentamicin. Five guinea pigs were injected with a single dose of both kanamycin (400 mg/kg, s.c.) and furosemide (100 mg/kg, i.v.), 5 animals received gentamicin (100 mg/kg, i.p.) for 10 days, and 5 untreated animals served as controls. After 7 days, vestibular function was assessed by measuring vestibular short-latency evoked potentials (VsEPs) to linear acceleration stimuli and cochlear function by auditory brainstem responses (ABRs) to clicks. Hair cell densities were determined in phalloidin-stained whole mounts of the utricles and saccules, and in midmodiolar sections of resin-embedded cochleae. Co-administration of kanamycin and furosemide had no significant effect on VsEPs and hair cell densities in the utricles and saccules were not reduced. ABR thresholds were increased to a great extent (by ∼60 dB), and histologically a severe loss of cochlear hair cells was observed. The effect of gentamicin, both on vestibular and cochlear function, was just the opposite. VsEP thresholds to horizontal stimulation were elevated and suprathreshold amplitudes showed a decrease, whereas cochlear function was not reduced. With this protocol, we have a tool to selectively induce cochlear or vestibular damage, which may be of interest to researchers and clinicians alike.

Does Vestibular End-Organ Function Recover after Gentamicin-Induced Trauma in Guinea Pigs?

“…Later peaks in the VsEP do not solely originate from nuclei in the vestibular pathway, but may originate from the cranial nerve nuclei [Li et al, 1997: cat] or the auditory nuclei [Böhmer, 1995: chinchilla;Oei et al, 2001;Bremer et al, 2012: guinea pig]. Three control experiments on the VsEP in our laboratory showed that the N 1 peak of the VsEP originates from the end-organ vestibular organs [Bremer et al, 2012]. Furthermore, destruction of the cochlear hair cells with a single cotreatment of kanamycin and furosemide, which leaves the vestibular hair cells intact, did not reduce the N 1 [Bremer et al, 2012], which confirmed that the N 1 is mainly vestibular.…”

“…The skin on the skull was locally infiltrated with lidocaine 2%. An incision was made from the vertex until 2 cm rostral of the bregma [Bremer et al, 2012]. The skin including periost was incised and lateralized for exposition of the skull.…”

“…The VsEP typically consists of 3 or 4 prominent waves occurring within 5 ms after stimulus onset. The positive and negative peaks, P 1 and N 1 , occurring with latencies of about 0.75 and 1.0 ms, respectively, have been demonstrated to be reliable indicators for otolith organ function in various rodents [Böhmer, 1995: chinchilla;Jones and Jones, 1999: mouse;Oei et al, 2001;Bremer et al, 2012;Chihara et al, 2013: guinea pig]. Later peaks in the VsEP do not solely originate from nuclei in the vestibular pathway, but may originate from the cranial nerve nuclei [Li et al, 1997: cat] or the auditory nuclei [Böhmer, 1995: chinchilla;Oei et al, 2001;Bremer et al, 2012: guinea pig].…”

“…Thus, long-term effects of ototoxic damage on the otoliths reflected by direct parameters of end-organ function are not known. To address this, we recorded vestibular shortlatency evoked potentials (VsEPs) which reflect end-organ function in guinea pigs Jones and Jones 1999;Oei et al, 2001;Bremer et al, 2012;Chihara et al, 2013]. At various times before and after gentamicin treatment VsEPs were recorded in a longitudinal design.…”

“…At various times before and after gentamicin treatment VsEPs were recorded in a longitudinal design. The VsEPs were evoked with linear accelerations in 3 directions in order to assess both saccular and utricular function [Bremer et al, 2012]. Histological evaluation followed after assessment of function.…”