Quantitative Evaluation of Nitromin Ototoxicity and Analysis of Compound Action Potential Responses in Electrocochleography in Guinea Pig Cochlea

Abstract

Listen

Translate article

Quantitative evaluation of Nitromin ototoxicity was examined in guinea pigs given one dose of the drug intravenously. Pathological changes in the cochlear sensory hair cells were then observed under a light microscope following surface preparation after cold phosphate-buffered 2% osmic acid solution fixation. Possibility of frequency specificity of tone pip electrocochleography and modification of input-output functions of cochlear whole-nerve action potentials in absence of outer hair cells were studied by examining the relationship between the degree of outer hair cell damage and the cochlear AP responses.I) Degree of outer hair cell damage:At the initial stage, the degeneration of the outer hair cells were the most extensive in the basal turn, and least in the third turn. With the advance of degenerative changes, the damage in the lower turns proceeded rapidly and became more extensive than that in the apical turns.The outer hair cells in the first row were significantly more vulnerable in each coil. However, at the initial stage, the outer hair cells in the fourth coil were more vulnerable in the third than the first row.II) Cochlear AP responses in guinea pigs treated with drugs:Both the prolongation of minimum latency and increase in the width of the AP-SP wave form complex of AP responses to low-frequency (1, 2KHz) tone pip were more prominent than to high-frequency (4, 8KHz) one.Decrease of the maximum amplitude of AP responses to low-frequency (0.5, 1, 2KHz) tone pip was greater than to high-frequency (4, 8KHz) one, comparing each decrease of that with the degree of the outer hair cell damage in respective coils. Therefore, changes of each parameter at high intensities indicated the decrease of the number and the degree of synchronization of the activity of the auditory units located in the lower turns, especially in the basal turn, regardless of the frequency of the stimulation tone.The elevation of the threshold of AP response to each frequency tone pip was comparatively correlative with the degree of outer hair cell damage in each coil, respectively.For the input-output curves of AP responses to 4 and 8KHz tone pips, the L-curve disappeared according to the advancement of the degenerative changes, after which the maximum output of the H-curve decreased respectively to 22.9% and 24.1% of each average output in the normal group, despite the finding that almost all the inner hair cells survived. Accordingly, it was considered that the outer-hair-cell units had a significant influence on the synchronous firing of the inner radial fibers connecting to the inner hair cell system, though the L-response and the H-response component mainly depended on the auditory units originating in the outer and inner hair cells, respectively.At higher intensities, the polarity of SP as the earlier fraction of AP-SP wave form complex, changed to negative with 4 and 8KHz tone pips and click stimulations in case of severe outer hair cell damage in the lower turns.