Our objective is to find the cause of and a cure for Meniere's disease by developing an animal model and using such a model for treatment. Endolymphatic hydrops, a consistent pathological feature in Meniere's disease, is believed to be due to an increase in endolymphatic pressure and is suspected to cause a sensation of fullness of the ear, tinnitus, dizziness, and hearing loss. Although consistent endolymphatic hydrops can be produced by ablation of the endolymphatic sac in animals, some doubt remains as to whether malfunction of this structure is really the sole cause of Meniere's disease. Because endolymphatic hydrops is shown in other pathological conditions in both human and animals, different etiologies are suspected to produce a similar condition. We will explore the possibility of producing hydrops by other methods. One of our approaches is to apply a slightly higher pressure to the inner ears of normal animals to disturb the homeostasis of inner ear fluids. The pressure, in a magnitude which will cause ischemia of the inner ear, will be applied through the middle ear cavity. The pressure will be an intermittent positive and/or alternating positive and negative pressure which will affect the secretory activity of the stria vascularis, spiral ligament, and vestibular dark cells. Another approach is to administer enzyme inhibitors of secretory cells directly into the inner ear. Based on our own finding that Ca++-ATPase activity in the spiral ligament of the hydropic inner ear is decreased, an inhibitor of this enzyme, vanadate, will be introduced into the normal inner ear. An inhibitor of Na+,K+-ATPase, ouabain, will be infused into the inner ear to affect secretory function of the stria vascularis. Dizziness and the cause of dizziness will be investigated. The middle ear pressure in animals with endolymphatic hydrops will be increased to determine the effect on vestibular symptoms. The theory of the membrane rupture will be tested by rupturing the distended membranous wall by increasing the endolymphatic pressure. With a theory that the vestibular symptoms are not due to rupture of the membranes, osmotic and hydrostatic pressures will be increased by infusion of Ca+ + into the endolymph compartment without rupturing the membranes. For treatment, attempts to decompress endolymphatic hydrops will be made by administering the steroid aldosterone and a potassium-sparing diuretic drug, Dyazide. Gentamicin will be administered into the cistern of the vestibule to affect primarily the vestibular sensory cells.

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National Institute on Deafness and Other Communication Disorders (NIDCD)
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Hearing Research Study Section (HAR)
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Massachusetts Eye and Ear Infirmary
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