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Conclusion: In the present study, classification of the patterns of 3D CT images of the ductus reuniens (reuniting duct) (RD), saccular duct (SD), and endolymphatic sinus (ES) gave more precise information for assessing the pathological condition of Meniere's disease (MD) than our previous study., Objective: This study attempted to provide more detailed information on MD by classifying the patterns of 3D CT images of the RD, SD, and ES in patients with MD., Methods: We examined the ears of 62 patients with definitely diagnosed unilateral MD based on the criteria of the Committee on Hearing and Equilibrium of the American Academy of Otolaryngology-Head and Neck Surgery (AAO-HNS) using 3D CT. The 3D CT images of bony grooves of RD, SD, and ES (BRD, BSD, and BES) were classified into patterns according to aspects of their patency., Results: BRD could be classified into six types by assessing their patency defined using the criteria in this study. In the ears on the affected side of patients with MD, the BRD, BSD, and BES lost continuity in 3D CT images along their bony routes and were significantly different from normal healthy ears (p < 0.01). There were no significant differences among each stage of MD in the distributions of BRD and BES except for BSD.

Strial marginal cells are known to secrete K+ into endolymph via apical IsK/KvLQT1 (IKs) channels. Regulation of K+ secretion by several hormones is important for inner ear homeostasis but the role of vasopressin in the cochlea is still controversial. We examined the effect of arginine vasopressin (AVP) on marginal cells in the middle turn of the neonatal rat cochlea using nystatin-perforated whole-cell recordings at 24 degrees C. Whole-cell capacitance was 27.3 + 1.1 pF (n = 31). AVP(10(-8) M) gradually increased the IKs channel current in 30 min from the basal (1.1 +/- 0.3 pA; n = 6) to the peak level (714.7 +/- 197.5 pA; n = 6). The deactivation curve of the IKs channel current was best fitted to a biexponential function. 1-Deamino-D-arginine vasopressin (DDAVP; 10(-8) M; n = 5) and 8-bromo-cAMP (10(-4) M; n = 5) also mimicked the effect of AVP with similar time courses. However, 10(-9) M AVP (n = 7) and DDAVP (n = 5) showed no response. The majority of the increase in the IKs channel current caused by 10(-8) M AVP, 10(-8) M DDAVP or 10(-4) M cAMP was blocked within 2 min by the application of chromanol 293B (10(-5) M), a selective blocker of the IKs channel. Our results demonstrate that AVP increases the IKs channel current in marginal cells of the neonatal rat at a concentration of 10(-8) M, and the fact that 8-bromo-cAMP (10(-4) M) and DDAVP (10(-8) M) also showed similar effects at 24 degrees C may suggest the involvement of V2 receptors and the subsequent activation of the cAMP signal pathway.

Evaluation of some 200 endolymph proteins indicates that they are predominantly derived from plasma. However, the profile of endolymph proteins is remarkably similar to that of perilymph and entirely different from that of plasma. This supports the current consensus that perilymph rather than plasma is the (direct) source of endolymph. Although the levels of total protein of endolymph is extremely low, a few plasma-derived proteins, such as apolipoproteins J and D, are selectively enriched, conceivably for protection of cell membranes bounding the endolymphatic space. A small number of endolymph proteins, mostly glycosylated ones, are continually secreted into the endolymph by specialized epithelial cells, primarily for the maintenance of the structural and functional integrity of the extracellular superstructures comprising tectorial membrane, otoconial complex (membrane) and cupula. These complex macromolecules cannot be eliminated in the periphery of the compartment, but are transported to the endolymphatic sac for elimination. Impaired clearance of these negatively charged macromolecules by a dysfunctional endolymphatic sac will contribute to the chemical imbalance of endolymph which accompanies long-standing endolymphatic hydrops, and may be one of the reasons for the observed loss of function.

The endolymphatic potential is assumed to result from active K transport into the endolymphatic compartment and passive K diffusion in the opposite direction. However, in several in vivo experiments, changes in the endolymphatic potential differed from those in the endolymphatic K concentration. Moreover, in in vitro experiments, a negative endolymphatic potential was observed in the presence of ouabain without K gradient between the two compartments. These observations suggest that the coupling between the K transport and the genesis of the endolymphatic potential is not tight. Several factors may separately influence the endolymphatic potential and the K transport such as the acid-base equilibrium, the integrity of Reissner's membrane, the hormonal status, and the Na transport.

Secretion of endolymph is localized in some structures of the inner ear, namely the stria vascularis in the cochlea and the dark cells in the vestibule and in the lower vertebrate inner ear. In isolated semicircular canal it is possible to study separately the endolymphatic composition in the ampulla, which contains the dark cells, and in its non-ampullar part, which is devoid of these cells. Further, in vitro preparation of the semicircular canal provides access to both faces of the epithelium so that different agents can be applied separately to the apical or to the basolateral membranes of the epithelium. In this structure, the following results were obtained: i) in vitro, the semicircular canal secreted a K-rich, positively polarized fluid; ii) this fluid was secreted only in the ampulla of the semicircular canal; iii) the secretion of endolymph was dependent on basolateral Na+, K(+)-ATPase, inhibited by ouabain, and basolateral Na-K-Cl co-transporter, inhibited by bumetanide; iv) approximately 60% of luminal Na absorption occurred across a luminal Na channel inhibited by amiloride; v) the permeability of the paracellular pathway of the semicircular canal epithelium was 7.10(-7) cm/s. These results indicate that endolymph secretion involves basolateral Na+, K(+)-ATPase and Na-K-Cl co-transporter. An Na channel has been shown at the apical membrane.

Soybean agglutinin (SBA), Helix pomatia agglutinin (HPA), Ricinus communis agglutinin-II (RCA-II), Limax flavus agglutinin (LFA) and wheat germ agglutinin (WGA) were employed to determine the localization of specific carbohydrates on thin sections of lowicryl K4M embedded guinea pig striae vasculares using the lectin-gold and glycoprotein-gold techniques. SBA, HPA and RCA-II gold labeling was observed in many of the cytoplasmic vesicles, endosomes and apical tubules located in the supranuclear region as well as on the microvilli and micropinocytotic invaginations of the luminal plasma membrane of the marginal cells. LFA labeling was found on the basal plasma membrane of the marginal cells as well as in the basement membrane of the perivascular spaces. WGA binding sites were detected along the plasma membrane of all types of cells constituting the stria vascularis. Our present results revealed that the membranes of internalization and many of the cytoplasmic vesicles, endosomes and apical tubules in the supranuclear region of the marginal cells are associated together and it is suggested that these structures may be related to the regulation of endolymph.

Potassium canrenoate (PC) is a diuretic with antialdosterone action, reducing the reabsorption of sodium in the efferent renal tubules. This drug has been reported to damage only the marginal cells of the stria vascularis in the cochlea. The perilymphatic space of the guinea pig cochlea was perfused with an artificial perilymph containing 5 x 10(-3) M potassium canrenoate. Following the onset of perfusion, the endocochlear dc potential (EP) gradually declined to around 10 mV but did not become negative even when the perfusion was continued. A similar decrease in EP was observed in kanamycin-deafened guinea pigs. When the respirator was turned off and perfusion discontinued, a large negative EP appeared during 5 min of anoxia in normal guinea pigs but not in the kanamycin-deafened guinea pigs. The decreased EP recovered to preanoxic level after resumption of ventilation. The cochlear microphonics (CM) also gradually declined in parallel with the EP. The summating potential (SP) showed only a minor change. The potassium ion activity in the endolymph decreased slightly but the sodium ion activity remained unchanged during perfusion. These findings suggest that the main target of the PC is the cells of the stria vascularis.

In the chinchilla, quantitative changes in strial thickness, area of the endolymphatic space, serum osmolality, and serum levels of glycerol, glucose, total protein sodium, potassium and chloride were determined at 1, 2, 3 and 5 h after the intraperitoneal administration of 6 g/kg glycerol. The serum osmolality, glycerol, glucose and potassium levels increased, while serum sodium and chloride decreased. Quantitative changes in cochlear structure included an increase in strial thickness and a decrease in area of the endolymphatic space. In all the animals (n = 50), the increase in strial thickness was closely correlated (correlation coefficient r = 0.57) to an increase in serum osmolality. This correlation with strial thickness improved (R = 0.71) when the interval between injection and animal sacrifice was used in combination with serum osmolality. The increase in stria thickness was also closely correlated to an increase in serum glycerol and to a decrease in serum chloride. A decrease in endolymphatic volume was found most consistently at 3 h after the i.p. administration of glycerol.

Healthy guinea pigs were exposed to broadband noise at 115 dBA for 7 days. When perfusion of the scala vestibuli was carried with artificial perilymph containing 43K, the 43K concentrations in the perilymph of the scala tympani were very low in both control and noise-exposed guinea pigs. The transport rate constant for K+ was computed by utilizing compartmental analysis. The results indicate that exposure to noise at 115 dBA for 7 days does not alter the permeability to K+ of Reissner's membrane or the lateral wall of the cochlear duct but does decrease K+ conductance of the organ of Corti.

In a previous paper we demonstrated physiologically a sensitive period for acoustic trauma in the rat pup cochlea, with a maximum at 22 days of age. Seven or 60 days after noise exposure these 22-day exposed rats were used for light and electron microscopy. At 7 days, surface preparation revealed restricted damage to the basal cochlear coil, while with electron microscopy signs of cytoplasmic degeneration appeared in the great majority of basal coil structures. Two months after noise exposure these structures have completely degenerated. These results were discussed in terms of mechanical versus metabolic explanations of the critical period for acoustic trauma.

[3H]Dihydrostreptomycin was given intramuscularly to young pigmented guinea pigs and rats. Whole-body autoradiography, combined with densitometric measurement of the blackening of the autoradiograms, and liquid scintillation counting were used to determine the levels of radioactivity in the inner ear in relation to blood and other tissues. It was found that there was an accumulation of radioactivity in the perilymph of both the cochlear and vestibular parts of the labyrinth. The labelling of the endolymph was weak. The levels of radioactivity in the membranous linings of the labyrinth including the areas covered with the neuroepithelial structures, were about the same as in the perilymph. The general distribution pictures were characterized by a localization of radioactivity in extracellular tissues, such as cartilages and connective tissues and by strong labelling of the kidney cortex. The preferential uptake in the perilymph indicates a route by which the inner ear hair cells can be exposed to high levels of aminoglycoside antibiotics.

Ca++ concentrations and d.c. potential within the endolymphatic space of the cochlear duct and the semicircular canal following acute anoxia or ethacrynic acid intoxication (100 mg/kg i.v.) were measured by means of double-barrelled microelectrodes. Ionic calcium content and d.c. potential were found to change in a roughly biphasic fashion after either intervention. The maximal increase in Ca++ concentration coincided with the decline in the d.c. potential, which after a rapid decline finally reached and maintained negative voltages. This phenomenon was more pronounced in the cochlear part than in the semicircular canal. A model of calcium homeostasis is proposed in an attempt to reconcile the data presented with earlier evidence.

Radioactive-labelled sodium does not penetrate via the round window in the inner ear of guinea-pigs. The findings reported confirm the mechanism assumed by Arslan for his "osmotic induction" surgery in the treatment of morbus Menière.

After obliteration of endolymphatic sac and duct, no significant alteration in d.c. potential, K+ activity or protein content during the development of endolymphatic hydrops could be observed. The K+ activity of endolymphatic sac was only one-ninth of that in the cochlear part of the endolymph. After injection of Thorotrast into the endolymphatic sac, aggregated particles were found in the cochlear endolymph 2 days later. Ethacrynic acid (60 mg/kg) caused a decrease in K+ activity in the cochlear endolymph, but an increase in the endolymphatic sac. Intercellular edema was observed both in stria vascularis and in endolymphatic sac by light and electronmicroscopy after ethacrynic acid administration. These results suggest the existence of an active transport mechanism in the endolymphatic sac epithelium.

The efflux of Na-24 was investigated in isolated labyrinths from a membrane section containing stria vascularis and spiral ligament in artificial endolymph medium. The efflux curves were calculated and compartmental analyses were made. The theoretical possibility of a exchange of sodium between compartments connected in different ways was considered. The calculated values of rate constant of transmembranal sodium fluxes are 0.0282+/-0.0052 min-1 and the half-time of the exchange of sodium between intracellular compartments is 24.27+/-4.53 min. The distribution of sodium in tissue with a commonly applied simplification gives 90% Na+ in the extracellular compartment and 3% Na+ in the intracellular compartment of the total tissue sodium content. The possibility of measuring the rate constant of transmembranal electrolyte fluxes in this tissue seems encouraging for future investigation of the mechanism by which they are transported.

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.

Guinea pigs were treated for 7 days by daily subcutaneous injection of methyl mercury chloride labeled with 14C, the total dose of which was 17 mg Hg/kg. In these animals the cochlear microphonics and whole-nerve action potentials were suppressed in the basal turn but there was no marked losses in the third turn of the cochlea. The endocochlear potential was not decreased in magnitude. At the end of the treatment there was no accumulation of mercury in the perilymph, endolymph and cerebrospinal fluid. Uptake and elimination of mercury in the cochlear fluids were studied in guinea pigs which were treated by a single intravenous injection of 203Hg-labeled methyl mercury, the dose of which ranged from 0.2 to 17 mg Hg/kg. The results indicated that mercury concentration ratio of the blood relative to cochlear fluids was comparable with the blood to plasma ratio reported previously. In contrast to lack of accumulation in the extra cellular environment, it is likely that tissues of the sensory end organs in the cochlea accumulated methyl mercury.

The oxygen tension (pO2) of endolymph of the guinea pig cochlea was measured during exposure to loud sound (12 kHz or high-pass noise; 110 dB SPL up to 1 h duration). A small, but significant, steady decline in mean pO2 was observed after both pure tone and high-pass noise exposure. The extent of the change in pO2 varied from 0-50% in individual animals, compared with unexposed control animals. All exposed animals had an extensive loss of compound action potential (CAP) thresholds at frequencies of 8-30 kHz. However, there was no relationship between the extent of the change in pO2 of endolymph and CAP threshold loss.

14C-glucose was used as a tracer to study the effect of phlorizin on glucose transport into perilymph and endolymph. The transport was found to be lowered in phlorizin-injected animals compared with that in normal controls. This inhibitory effect corresponding to a phlorizin-sensitive part of glucose transport was greater in the perilymphatic system than in the endolymphatic system. Pathways which are not affected by phlorizin, are considered to exist in both compartments of perilymph and endolymph.

The endolymphatic changes produced by an intravenous injection of 60 mg kg-1 ethacrynic acid were followed for up to 120 min using conventional and ion-sensitive (Na+, K+ and pH) microelectrodes in the rat. They were found to be caused by three distinct effects upon the endolymph system. Initially, the drug completely inhibited the strial potential-producing and cation-transporting processes. Recovery began quickly and was rapid at first. Then its rate declined considerably, probably due to diminution in strial energy production of delayed onset and prolonged duration. Coincident with these actions upon active transport, there was a decrease in the overall cation permeability of the endolymph system. This followed a different time course and affected K+ much more than Na+. The findings also provided further information about the mechanisms responsible for the normal endolymphatic composition. Qualitatively similar results were obtained in a subsidiary study on guinea pigs.

The endolymphatic effects of perilymphatic ouabain (2 X 10(-3) M) were followed in 3 guinea pigs using ion-sensitive micro-electrodes, enabling a Na+-related permeability increase to be identified. Investigation of the strial ultrastructural changes in 11 more animals revealed early swelling of the marginal cells, while the intermediate and basal cells became shrunken with characteristically dark-staining cytoplasm. The subsequent cellular alterations were complex. The findings suggest that a major function of the Na+-K+-activated ATPase is preservation of the normal intracellular environment, inhibition resulting in widespread indirect effects. General measures of strial function, consequently, do not document just ATPase inhibition.

A time sequence study of the effect of hemilabyrinthectomy on the endolymphatic sac was performed in mice. Light and transmission electron microscopy of the sac showed significant morphological changes of the epithelial lining and adjacent structures. Initially (2 and 4 days post-labyrinthectomy) the sac lumen was collapsed, but later (7 days post-labyrinthectomy) it was dilated or 'ballooned' and filled with a darkly staining homogeneous substance. This substance, which has been identified histochemically as a proteoglycan, appeared to be secreted from the epithelium of the endolymphatic sac. This finding suggests that the endolymphatic sac may be capable both of absorbing and of secreting endolymph.