The effects of histamine and its antagonists on the cochlear microphonic and the compound action potential of the guinea pig.

OBJECT: we studied the effects of histamine, the H1 receptor antagonist pyrilamine, and the H2 receptor antagonist cimetidine on the cochlear potential of guinea pigs (cochlear microphonic, CM; compound action potential, CAP). METHODS: histamine was applied into the cochlear perilymph at three different dosages (10 microM, 50 microM or 10 mM). Pyrilamine and cimetidine were applied at 50 microM each. RESULTS: histamine increased the CAP at 10 and 50 microM without any significant effects on the CM. The effects of histamine at 50 microM were suppressed by the 50-microM of pyrilamine and cimetidine. At 10 mM of histamine, CAP and CM amplitudes were significantly decreased. CONCLUSION: in low concentrations, histamine may act as an extracellular signal on inner hair cells (IHCs) or it may stimulate the afferent nerve by binding to their H1 and H2 receptors. A possible explanation for the inhibitory effects of histamine at 10-mM dosage was apparently found in that the effects of the high concentration may be supraphysiological; and furthermore, there is a difference in the mechanism by which histamine exerts its effects mediated by the histamine receptors on the cochlea.

Neurologic and otologic findings in Fisher's syndrome.

We performed neurologic and otologic examinations in 14 patients with Fisher's syndrome to determine whether its manifestations inducing acute ophthaloplegia, ataxia and areflexia may involve the auditory and vestibular systems. Tests included pure tone audiometry, auditory brainstem response, observations of nystagmus, smooth pursuit test, saccade test, optokinetic nystagmus test, and the caloric test. One patient showed downbeat nystagmus and lateral gaze nystagmus without restriction of eye movement, two patients showed dysmetria on saccades without restriction of eye movement, and three patients showed superimposed saccadic eye movement on smooth pursuit without lateral gaze nystagmus. The abnormalities in those six cases could not be explained by solely muscular weakness, but also appeared to involve the central oculomotor system. In the other patients, nystagmus could be explained by muscular weakness alone. Additionally, three patients, including two patients with dysmetria on saccades, showed a unilateral diminished response to caloric testing with no severe restriction of eye movements. In evaluating the auditory brainstem response of these three patients, one patient, who showed abnormality on the saccade and caloric tests, showed an elongation of wave I latencies and of wave I-III interpeak latencies at both ears, and one other patient showed an elongation of wave III-V interpeak latencies at both ears. This disorder may involve the peripheral and central auditory systems as well as the peripheral vestibular system.

PAF- and histamine-receptor antagonists lessen allergen-induced hearing impairment in guinea pigs.

We have demonstrated degranulation of mast cells in the endolymphatic sac as well as an increase in audiological threshold shift in the experimental animal models following antigen provocation. Mast cells, however, release such chemical mediators as histamine, platelet activating factor (PAF), and leukotriene due to an antigen-antibody reaction on the cell surface. The aim of this study was to clarify the major chemical mediators responsible for hearing impairment in the animal models following antigen provocation. Guinea pigs were actively sensitized with DNP-Ascaris and provoked with an injection of DNP-BSA. A significant audiological threshold shift was observed at 1, 10, 24, and 72 h following challenge with allergen. The peak shift was at 10 h; all changes were reversed after 7 days. This threshold shift was abolished by prior injection of either a histamine- or PAF-receptor antagonist to allergen, but not of a leukotriene-receptor antagonist. Results suggest that histamine and PAF are involved in the hearing impairment induced by allergen exposure in the guinea pig.

Recurrent hearing impairment and nystagmus induced by repeated antigen exposure in actively sensitized guinea pigs.

Although many studies have suggested a relation between allergy and Ménière's disease, the pathophysiology of this condition remains controversial. The aim of this study was to clarify whether an anaphylactic reaction in the inner ear can disturb hearing and equilibrium, and whether such disturbances recur in response to repeated anaphylactic reactions. Increases in audiological threshold, nystagmus, and endolymphatic hydrops were observed in response to a single exposure to antigen administered to actively sensitized guinea pigs. The increase in audiological threshold was maximal 10 h after antigen challenge (p < 0.005) and returned to the baseline level after 7 days. Nystagmus and the increase in audiological threshold induced by antigen exposure were inhibited by prior administration of pemirolast potassium (p < 0.05), an inhibitor of chemical mediator release from mast cells. A second challenge with antigen 7 days after the first also induced an increase in audiological threshold (p < 0.05) and nystagmus. These results suggest that studies of repeated antigen challenge in actively sensitized animal models may increase our understanding of the pathophysiology of Ménière's disease.