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The effect of furosemide on sodium and potassium concentrations in guinea-pig perilymph.

To observe the effects of furosemide on electrolyte concentrations in inner-ear fluids, experiments were performed on 286 normal guinea-pigs. Intravenous injection of furosemide (15 mg/kg) induced increases of Na concentration in scala tympani perilymph, scala vestibuli perilymph, and cerebrospinal fluid (CSF). K concentrations in both perilymphs and CSF were also increased by furosemide. The increased Na concentrations are thought to be due to the dehydration of body fluids induced by the diuretic action of furosemide. The increase of K concentrations in perilymphs could be attributable to either a characteristic action of furosemide on the electrolyte transport in the inner ear or a secondary change caused by a rise of K concentration in the endolymph.

Animals↗

Asymptotic analysis of a viscous cochlear model.

A model of cochlear macromechanics, involving a viscous cochlear fluid, is analyzed asymptotically for slowly varying membranes. The results exhibit the effect of viscosity on the amplitude, wavelength, and damping rate, and confirm the conclusion that viscosity is not important. However the method can be used on other models, such as those of cochlear micromechanics, where viscosity is more important.

Animals↗

Osmotically induced motility of outer hair cells: implications for Menière's disease.

Osmolarity changes in inner ear fluids have long been considered to be contributing factors to Menière's disease. Our present study demonstrates that small changes in the osmolarity of a surrounding in vitro medium induce fast contractions (hypo-osmotic solution) or elongations (hyperosmotic solution) in isolated outer hair cells of the guinea pig. These changes were reversible upon returning cells to iso-osmotic conditions. Up to five cycles of shape change could be sustained by these cells without obvious detriment to their morphology. These findings suggest that fluctuant changes in osmolarity of inner ear fluids can result in similar fluctuant changes of hair cell shape. Since the outer hair cells may control cochlear micromechanics and function by their active motility, osmotically induced abnormalities of cell dimensions and motility may contribute to the audiological manifestations of fluctuant hearing loss.

Animals↗

Elemental composition of the mature inner ear.

An X-ray energy dispersive analysis was performed on the mature serial sectioned freeze-dried mammalian labyrinth (CBA/CBA mouse). The elemental distribution in the endolymphatic and perilymphatic spaces revealed similar results as have been reported in the literature when withdrawing fluid for microanalysis. The cupulae of the vestibular organs showed only minimal relative peak intensities of chlorine and potassium in contrast to the tectorial membrane in the cochlea with elemental identification also of sodium, sulphur and calcium. A difference in structural composition is therefore likely between these two tissues.

Animals↗

Electrophysiological and biochemical findings in four cases of Meniere's disease.

In 4 cases of Meniere's disease, E.P., concentrations of Na, K, Cl, and protein, and osmolality were determined in endolymph from the basal coil of the cochlea. In 3 cases, endolymph was found normal in nature as compared with normal animals. In one long-standing (11 years) case, a strial dysfunction was evidenced. In 2 cases, the surgical treatment consisted in the mere withdrawal of endolymph. This resulted in the transitory aggravation of the hearing loss. This observation might suggest that, at the considered stages of the disease: 1) hearing loss is not related to the excess of fluid; 2) the rate of endolymph production averages 0.35 microliter per day; 3) the water displacement induced by the glycerol test concerns rather perilymph than endolymph; 4) any pharmacological or surgical therapy aiming at reducing the excess of endolymph is unlikely to succeed as far as hearing is concerned.

Adult↗

Pressure relationship between perilymph and endolymph in guinea pigs.

The pressure difference between the perilymph and the endolymph was studied in guinea pigs, using two sets of a servo-nulling system. Asphyxia caused characteristic pressure changes both in the perilymph and in the endolymph, but no pressure difference was seen between them. When the perilymphatic space was opened to the atmosphere, asphyxia did not cause such dynamic pressure changes either on the perilymph or the endolymph. An increase in the perilymphatic pressure induced by the infusion of artificial cerebrospinal fluid into the subarachnoid space resulted in an increase in the endolymphatic pressure, but no pressure difference between the endolymph and the perilymph was evident, regardless of the patency of the vestibular aqueduct. The authors conclude that the endolymphatic pressure is dependent on the perilymphatic pressure and there is no pressure difference between them.

Animals↗

Modulation of inner ear pressure in experimental endolymphatic hydrops.

Physiologic study of the guinea pig model of endolymphatic hydrops has been used to better understand the manifestations of Meniere's disease. Quantitative vestibular function testing demonstrates some changes in the hydrops subjects, especially if an additional stress such as postural inversion is imposed. Understanding the hydrodynamic changes on the endolymphatic and perilymphatic fluids by the hydrops condition as well as postural inversion may be useful in explaining the vestibular findings. These pressure effects may alter the micromechanics of the inner ear or possibly induce a relative vascular ischemia. Auditory dysfunction is speculated to occur through similar mechanisms.

Animals↗

Cochlear neurons: frequency selectivity altered by perilymph removal.

Removal of perilylmph from the scala tympani of the guinea pig cochlea reversibly broadened the tuning curves of single spiral ganglion cells emanating from the basilar membrane. Thus, fluid continuity along the membrane is essential for normal cochlear function, in particular for sharp neural tuning curves. These data reveal a possible source of error in some estimates of basilar membrane motion and suggest a reappraisal of current concepts of the mechanism of sharp tunig in primary auditory nerve fibers.

Acoustic Stimulation↗

Endolymphatic hydrops and III type allergic reaction.

IgG antibody and complement are both present in endolymphatic fluid, and it is possible that immune complex may form in endolymphatic fluid. However, there are still obscure points as to whether endolymphatic hydrops is due to immune complex, but it is quite possible that it is only one causative factor in endolymphatic hydrops.

Animals↗

A new immunohistochemical method for the detection of gentamicin in inner ear fluid compartments.

A new method was developed for frozen section detection of antigens that natively occur in the cochlear peri- and endolymph. A combination of immuno-histochemistry and immunoblot assay enabled topological and quantitative detection of small and hydrophilic molecules (such as the aminoglycoside antibiotics) in frozen sections of the inner ear compartments (scala tympani, scala vestibuli and cochlear duct). A selective localization is possible in the peri- and endolymphatic region of each coil of the cochlea. During sectioning of the cochlea, a small piece of a nitrocellulose membrane is placed to the surface of the intersection and briefly warmed. The sections are cut, simultaneously attached to a nitrocellulose membrane on which the aminoglycoside antibiotics remain adsorbed without any fixation procedure. Using this method, immunoincubation to detect gentamicin was performed in a way usually done in western blot analysis. Results with two different enzyme reactions with the enzyme conjugated to a second antibody (i.e., dye as substrate and the chemiluminescence detection system) are presented and compared. This histoimmunoblot assay provides a general non-radioactive and sensitive immunohistochemical tool for the localization of compounds occurring in extracellular body fluid compartments. For inner ear research this method now enables the investigation of the penetration and distribution of therapeutics in peri- and endolymphatic sites and can even be applied to separately quantifying concentrations of a substance in different coils of the same cochlear section.

Animals↗

Fluid dynamics in sudden sensorineural hearing loss.

A change in fluid pressure in one intracochlear compartment also causes a pressure gradient in the other. Thus, one membrane break is likely to cause a secondary break. We have presented indirect evidence for such double membrane breaks in sudden hearing loss, and argue that one of the two breaks can heal spontaneously while the other remains active.

Adult↗

Experimental alteration of physiological state of inner ear fluids.

Mechanisms of endolymphatic hydrops formation in the inner ear are not yet fully understood. The available knowledge of the composition and the function of inner ear fluids, of mechanisms for maintenance of microhomeostasis, and the possible factors responsible for hydrops formation were reviewed. The nature of the functional barrier systems of the inner ear was investigated by measuring the amount of intravenously or intracisternally injected test substances which entered the perilymph. Based on studies of the osmotic relationship between the blood and the perilymph, an hypothesis of hydrops formation is proposed. The hypothesis predicts an osmotic imbalance, resulting from an upset of the homeostasis between the fluid compartments and the tissues of the inner ear, as a factor responsible for endolymphatic hydrops formation. An osmotic imbalance can be induced by various experimental conditions including metabolic disorders. The results of animal experiments strongly suggest the necessity of further survey of metabolic imbalance in Ménière's patients.

Adenosine Triphosphatases↗

Fluid kinetics of endolymph during rotation.

Rotatory vestibular excitability is discussed on the basis of a fluid-mechanical theory. The principle of this theory, already described for caloric excitation, is that appropriate stimulus causes flows within the endolymph. Experimental and mathematical approaches indicate these flows to be essentially the same in caloric as in rotatory stimulation. The direction of a horizontal nystagmus is apparently determined by a circuit of endolymph in the lateral part of the ampulla.

Endolymph↗

The effect of changes in endolymphatic ion concentrations on the tectorial membrane.

The development of a new preparation technique has allowed the effects of fluid-substitution experiments on the tectorial membrane (t.m.) to be studied morphologically and not only, as previously, electrophysiologically. The organ of Corti and t.m. were examined in situ, unfixed and with in vivo-like ionic conditions under light-microscopical control (differential-interference-contrast, magnification 400--800X). An irreversible shrinkage of the marginal and middle zones of the t.m. was observed under the influence of Na+ ions (substitution of endolymph with artificial perilymph). This shrinkage is also seen in specimens prepared for scanning electron microscopy after perfusion of scale media with perilymph. If endolymph is replaced by an isotonic solution of EDTA (ethylenediaminetetraacetate) the t.m. can swell in its vestibulo-tympanal extent, e.g. from 39 to 72 microns. This swelling is reversible on addition of CaCl2. Although the size of the t.m. is not influenced to any great extent by changes in fluid osmolarity, reduction of H+ ion concentration leads to a minimal state of hydration of the protobril system at pH 4.3 (i.e. region of isoelectric point). The mechanism of Na+ and Ca2+ effects are discussed. These results indicate that the subtectorial space is morphologically separated from the scala media proper by the marginal zone.

Animals↗

Experimental study on Meniere's disease.

Experimental hydrops caused by underabsorption of endolymphatic fluid is a model of remissional stage of Meniere's disease. In this study, another type of model, ie, hydrops caused by overproduction of endolymphatic fluid, was accomplished by applying various pressures into scala media through a micropipette via stria vascularis. This type of hydrops could be a model of attacks of Meniere's disease. By using two types of the model, effects of glycerol administration and of opening the endolymphatic sac were discussed.

Animals↗

Application of loop diuretics for treatment of sensorineural hearing impairment. Experimental and clinical study.

In a series of animal experiments on guinea pigs and rats, conducted in an attempt to find a better solution for the treatment of sensorineural hearing impairment and tinnitus-known as diseases almost impossible to heal-it was revealed electrophysiologically, biochemically and electronmicroscopically that loop diuretics, referred to as ototoxic drugs, cause an increased amount of the therapeutic preparation to transfer to the inner ear fluid. It is concluded, on the basis of the encouraging results of these experiments, that combined medication with metabolic activator, steroid hormone and loop diuretics is significantly more effective in improving the symptoms of patients with inner ear deafness and tinnitus.

Animals↗

[Pathophysiological aspects of therapeutic procedures in Menière's disease (author's transl)].

Meniére's disease is a nosologic entity. Its underlying pathophysiological mechanism is based on a disturbance of the quantitative correlation between peri- and endolymph volume on the one side and on a qualitative disorder of sodium and potassium concentration in the inner ear fluids on the other, resulting in a disregulation of osmotic pressure within the labyrinth. However, a critical review of the current literature as well as personal observations confirm that at the present time the scientific basis of a causal therapy is still lacking. Hence, both conservative and surgical treatment of Menière's disease does not allow to cure the cause but only some of the symptoms.

Humans↗

[Comparative analysis of the variants of experimental intra-aural pharmacophysical intervention].

The permeability of the blood-brain barrier of rabbits was measured in response to different methods of endaural pharmacophysical intervention and intravenous injection of radioactive DL (2,3-3H2) leucine. The concentration of labelled leucine was measured in the inner ear fluids. The experiments were performed using 28 rabbits. The maximum amount of the drug entered the labyrinth as a result of endaural superphonoelectrophoresis. In this case the positive effect was reached after a smaller number of therapeutic sessions. This method is recommended for clinical treatment of cochleovestibular lesions.

Animals↗