Study on Ototoxicity of Gentamicin Injected into the Cerebrospinal Fluid Space of Rabbits

Abstract

The ototoxicity of gentamicine is well-known. Ototoxic abnormalities were examined by electrocochleography in adult rabbits after daily gentamicin injections of 0.05mg/kg (group I), 0.1mg/kg (group II), 0.25mg/kg (group III), 0.5mg/kg (group IV), and saline (control) into the cerebrospinal fluid space. Electrodes were implanted in the middle ear, and action potential (AP) responses to clicks were recorded. AP changes, especially input-output function curve changes were observed daily. The general condition and changes in equilibrium of the rabbits were also noted. The cochleas were then examined histologically.
1) AP changes: No changes were seen in the controls or group I. In one of the four rabbits in group II, AP amplitude decreased and then AP disappeared. In the other three no changes were observed. In all rabbits in groups III and IV, AP decreased rapidly and disappeared. The total dose of gentamicin was 2.5mg/kg in group III and 3.1mg/kg in group IV. The input-output curve changes of gentamicin-damaged rabbits were; early disappearance of L-curve and persistence of H-curve only. This change suggests that the stimulation function represented by the L-curve is more vulnerable to damage by gentamicin than in the H-curve.
2) General condition and equilibrium disturbance: No abnormalities were seen in the controls or group I rabbits. The rabbit which showed AP changes in group II and all group III and IV rabbits showed weight loss, reduced activity, and equilibrium disturbances, including positional abnormality, indicating vestibular damage.
3) Histological findings: Rabbits in which the AP disappeared were examined histologically. Marked changes were seen in the cells of the organ of Corti. The stria vascularis and the spiral ganglion cells were normal. Almost all the inner and outer sensory hair cells of all the cochlear turns were damaged.