ABSTRACT
BACKGROUND: Transtympanic administration of gentamicin may be suitable to achieve unilateral vestibular ablation, in order to control unilateral Ménière's disease. In low doses, gentamicin appears to affect selectively the vestibular system, with relative sparing of the cochlea. An experimental study on guinea pigs was conducted to determine what single dose of gentamicin would produce a unilateral vestibular organ lesion when applied to the middle ear. STUDY DESIGN: Experimental and prospective. METHODS: Four groups of guinea pigs received different gentamicin doses (1, 5, 10 and 25 mg) administered to the middle ear. The animals' vestibular organs were then assessed by scanning electron microscopy, in order to quantify the level of vestibular damage. RESULTS: Study of the utricular macula and the ampullar crista of the lateral semicircular canal revealed vestibular neuroepithelial lesions in all infused ears. CONCLUSIONS: The severity of the vestibular neuroepithelial lesions was dose-dependent. Lower gentamicin doses were observed to damage vestibular structures more than cochlear structures.
Subject(s)
Anti-Bacterial Agents/pharmacology , Ear, Middle/drug effects , Gentamicins/pharmacology , Animals , Anti-Bacterial Agents/administration & dosage , Dose-Response Relationship, Drug , Ear, Middle/ultrastructure , Female , Gentamicins/administration & dosage , Guinea Pigs , Male , Microscopy, Electron, Scanning , Saccule and Utricle/drug effects , Saccule and Utricle/ultrastructure , Semicircular Ducts/drug effects , Semicircular Ducts/ultrastructureABSTRACT
Afferents of the frog semicircular canal (SCC) respond to acetylcholine (ACh) application (0.3-1.0 mM) with a facilitation of their activity while frog saccular afferents respond with suppression (Guth et al., 1994). All recordings are of resting (i.e., non-stimulated) multiunit activity as previously reported (Guth et al., 1994). Substitution of 80% of external chloride (Cl-) by large, poorly permeant anions of different structures (isethionate, methanesulfonate, methylsulfate, and gluconate) reduced the suppressive effect of ACh in the frog saccular afferents. This substitution did not affect the facilitatory response of SCC afferents to ACh. Chloride channel blockers were also used to test further whether Cl- is involved in the ACh suppressive effect. These included: niflumic and flufenamic acids, picrotoxin, 5-nitro-2-(-3-phenylpropylamino)benzoic acid (NPPB), and 4,4'-dinitrostilbene-2,2'-disulfonic acid (DNDS). As with the Cl- substitutions, all of these agents reduced the suppressive response to ACh in the saccule, but not the facilitatory response seen in the SCC. The suppressive effect of ACh on saccular afferents is considered to be due to activation of a nicotinic-like receptor (Guth et al., 1994; Guth and Norris, 1996). Taking into account the effects of both Cl- substitutions and Cl- channel blockers, we conclude that changes in Cl- availability influence the suppressive effect of ACh and that therefore Cl- may be involved in this effect.