The severe ototoxic interaction of the combined administration of furosemide and aminoglycoside antibiotics (kanamycin, streptomycin and gentamicin) was studied in rabbits, and its mechanism clarified. Severe damage occurred not only in the inner ear but also in the kidney when both furosemide and aminoglycoside antibiotics were administered to rabbits. Kanamycin concentration after a single injection of kanamycin with furosemide was much higher not only in the perilymph but also in the cerebrospinal fluid and serum than that after a single injection of kanamycin alone. The ototoxic interaction following the combined use of furosemide and aminoglycoside antibiotics seems to be caused mainly by the inhibitory effect of furosemide on the excretion of aminoglycoside antibiotics from the kidneys.

The afferent and efferent nerve endings of the outer hair cells of the rabbit were investigated electron-microscopically. The afferent nerve ending was 1.4 X 2.0 microns in size and contained small vesicles, spherical mitochondria, and occasionally multivesicular bodies. The partially thick and dense membranes on either side of the synaptic cleft were observed and this region of the synaptic cleft was high in electron density. This area was considered to be an active zone of the afferent nerve ending. The efferent nerve ending was 4.0 X 6.0 microns in size and contained many synaptic vesicles, many oblong mitochondria, and multivesicular bodies. Synaptic vesicles were concentrated at some sites opposite the synaptic cleft. This area was thought to be an active zone where vesicles discharge their contents into the synaptic cleft. Furthermore, in some places of the synaptic cleft there were gaps (0.16 X 0.68 microns) which contained small vesicles. The gaps in the synaptic cleft have been briefly discussed.

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Rabbits were exposed to 100 dB pure-tone sound at 2 kHz for 2 h. Electron microscopy was used to study the relationship between changes in the outer hair cells, afferent nerve endings and efferent nerve endings. There was no relationship found between the degree of changes produced in the afferent nerve endings and that the outer hair cells. However, there was a relationship demonstrable between the degree of changes seen in the efferent nerve endings and the infranuclear region of the outer hair cells. These findings show that acoustic trauma will damage most the infranuclear region of the outer hair cells, while efferent nerve endings are injured next and least affected are afferent nerve endings.

The afferent and efferent nerve endings of the outer hair cells of the rabbit after acoustic exposure were investigated under the electron microscope. After acoustic stimulation, the afferent and efferent nerve endings of normal range were respectively 57 per cent and 64 per cent. This result suggests that half of the afferent and efferent nerve endings maintain their function under the conditions of this experiment. An abnormal inclusion body forming an oblong dense body and cistern in addition to the postsynaptic cisterna was observed. The active zone and the vesicular gap-structure of the synapse are discussed.