[Imaging characteristics of patients with large vestibular aqueduct syndrome and its relationship with the acoustically evoked short latency negative response].

Objective: To explore the imaging characteristics of large vestibular aqueduct syndrome (LVAS) patients and their relationship with the acoustically evoked short latency negative response (ANSR), so as to provide reference for the diagnosis of LVAS. Methods: Clinical data of 174 patients(334 ears) with LVAS diagnosed and treated by the Department of Otorhinolaryngology Head and Neck Surgery of the First Affiliated Hospital of Guangxi Medical University, from October 2009 to December 2017 were retrospectively analyzed, including 117 males and 57 females, aged from 5 months to 47 years old, with the median age of 4 years and 4 months. ABR and imaging data of patients were collected. Midpoint diameter and the outlet diameter of the vestibular aqueduct were measured on CT images, the midpoint diameter of the intraosseous parts and the extraosseous parts of enlarged endolymphatic sac(EES) were measured on MRI images. The correlation between the above measurements was analyzed by Pearson test using SPSS 17.0. According to whether ASNR was detected in ABR, the above data were divided into two groups, and the differences of the above imaging measurements were compared by the Independent-Sample Test. Results: The average midpoint diameter of the vestibular aqueduct was (1.87±0.58) mm (x±s, the following was the same), and the outlet diameter was (3.07±0.99) mm on CT; the average midpoint diameter of the intraosseous parts in enlarged endolymphatic sac(EES) was (2.39±1.37) mm, and the extraosseous parts was (2.50±2.18) mm on MRI. There was a correlation between the four measurements (P<0.05), among which the midpoint diameter of vestibular aqueduct was strongly positively correlated with the outlet diameter (r=0.760), and the remaining pairs were weakly correlated. ASNR was detected in 241 ears (72.16%,241/334) and undetected in 93 ears (27.84%, 93/334) of the 334 ears with LVAS. Midpoint diameter and the outlet diameter of the vestibular aqueduct in no ASNR group were smaller than the ASNR group, and the difference was statistically significant (t value was 2.814 and 2.754, P<0.05). There was no significant difference in the midpoint diameter of the intraosseous parts and the extraosseous parts of enlarged endolymphatic sac between the two groups, and the difference was no statistically significant(t value was 0.101 and 0.683, P>0.05). Conclusions: There is a strong positive correlation between the midpoint diameter of vestibular aqueduct and the outlet diameter in LVAS patients. There is a certain correlation between the size of vestibular aqueduct and the size of endolymphatic sac. The smaller the diameter of vestibular aqueduct, the lower the occurrence rate of ASNR.

Pathophysiologic Findings in the Human Endolymphatic Sac in Endolymphatic Hydrops: Functional and Molecular Evidence.

BACKGROUND: The endolymphatic sac (ES) is a cystic structure situated on the posterior fossa dura and is connected to the luminal space of the vestibular organ through the endolymphatic duct, which branches into the utricular and saccular ducts. Unlike the cochlea and vestibule, the ES does not contain sensory epithelium in its luminal space, and a single layer of epithelial cells line the luminal surface area. The ES in the inner ear is thought to play a role in the regulation of inner ear homeostasis, fluid volume, and immune reaction. If these functions of the ES are disrupted, dysfunction of the inner ear may develop. The most well-known pathology arising from dysfunction of the ES is endolymphatic hydrops, characterized by an enlarged endolymphatic space due to the accumulation of excessive endolymphatic fluid. Although, molecular identities and functional evidence for the roles were identified in animal studies, basic studies of the human ES are relatively uncommon compared with those using animal tissues, because of limited opportunity to harvest the human ES. METHODS: In this study, molecular and functional evidence for the role of the human ES in the development of endolymphatic hydrops are reviewed. RESULTS AND CONCLUSIONS: Although evidence is insufficient, studies using the human ES have mostly produced findings similar to those of animal studies. This review may provide a basis for planning further studies to investigate the pathophysiology of disorders with the finding of endolymphatic hydrops.

Dehydration effects of a V2 antagonist on endolymphatic hydrops in guinea pigs.

We investigated the influence of vasopressin type 2 receptor antagonist (OPC-41061; Tolvaptan) on experimentally induced endolymphatic hydrops (EH) in guinea pigs. In the first series, the endolymphatic sac (ES) of the left ear of all animals was electrocauterized. Four weeks after surgery, the animals were allocated to four groups: three systemic applications groups (saline, OPC 10 and 100 mg/kg) and a local round window (RW) OPC 1 mg/body application group. We examined the histopathology of the temporal bones and assessed volumetric changes of the endolymphatic space in the cochlea and saccule. In the second series, we investigated the effects of systemic and topical applications of OPC on plasma vasopressin (p-VP) concentrations and plasma osmolality (p-OSM). In the first series, we found that EH was reduced in the OPC 10 mg/kg systemic and OPC RW application groups. In contrast, EH increased in the OPC 100 mg/kg systemic application group. In the second series, neither p-VP levels nor p-OSM were significantly different among the non-OPC, OPC 10 mg/kg systemic, and OPC RW application groups. However, in the OPC 100 mg/kg systemic application group, the p-VP level was significantly higher than that in other groups, and p-OSM was higher than that in the non-OPC group. The systemic application of a low dose of OPC and topical application of OPC resulted in reduced EH in the face of minimal systemic effects (p-VP and p-OSM). These findings suggest that OPC-41061 may be one useful treatment option for EH.

Effects of endolymphatic sac decompression surgery on endolymphatic hydrops.

CONCLUSIONS: The present findings suggest that complete control of vertigo after endolymphatic sac decompression surgery (ESDS) does not always depend on improved vestibular function or reduced endolymphatic hydrops. Vertigo control is, however, associated with hearing stability. OBJECTIVE: Among surgical treatments for intractable Meniere's disease, ESDS is performed to preserve and improve inner ear function. We examined the correlation between changes in vertigo frequency and neuro-otologic function to understand the condition of the inner ear in patients whose vertigo was completely controlled after undergoing ESDS. METHODS: This was a retrospective cross-tabulation study. Between 1997 and 2001, we treated 52 patients with intractable vertigo using ESDS and followed the patients regularly for 2 years. Postoperatively we evaluated and recorded changes in vertigo attack frequency, maximum slow phase eye velocity, worst hearing level, and glycerol test results according to modified American Academy of Otolaryngology-Head and Neck Surgery 1995 criteria. RESULTS: We found no correlation between vertigo control and vestibular function. There was also no correlation between vertigo control and negative conversion of the glycerol test. There was a significant correlation between vertigo control and hearing control .

Mice deficient in H+-ATPase a4 subunit have severe hearing impairment associated with enlarged endolymphatic compartments within the inner ear.

Mutations in the ATP6V0A4 gene lead to autosomal recessive distal renal tubular acidosis in patients, who often show sensorineural hearing impairment. A first Atp6v0a4 knockout mouse model that recapitulates the loss of H(+)-ATPase function seen in humans has been generated and recently reported (Norgett et al., 2012). Here, we present the first detailed analysis of the structure and function of the auditory system in Atp6v0a4(-/-) knockout mice. Measurements of the auditory brainstem response (ABR) showed significantly elevated thresholds in homozygous mutant mice, which indicate severe hearing impairment. Heterozygote thresholds were normal. Analysis of paint-filled inner ears and sections from E16.5 embryos revealed a marked expansion of cochlear and endolymphatic ducts in Atp6v0a4(-/-) mice. A regulatory link between Atp6v0a4, Foxi1 and Pds has been reported and we found that the endolymphatic sac of Atp6v0a4(-/-) mice expresses both Foxi1 and Pds, which suggests a downstream position of Atp6v0a4. These mutants also showed a lack of endocochlear potential, suggesting a functional defect of the stria vascularis on the lateral wall of the cochlear duct. However, the main K(+) channels involved in the generation of endocochlear potential, Kcnj10 and Kcnq1, are strongly expressed in Atp6v0a4(-/-) mice. Our results lead to a better understanding of the role of this proton pump in hearing function.

Posterior semicircular canal dehiscence following endolymphatic sac surgery.

Posterior semicircular canal dehiscence is a rare otologic entity that presents with third window signs and symptoms. Petrous apex cholesteatoma, fibrous dysplasia, high riding jugular bulb, and eosinophilic granuloma have been reported to be associated with posterior semicircular canal dehiscence. Here we report a case of development of posterior semicircular canal dehiscence following an endolymphatic sac surgery for the first time.

von Hippel-Lindau disease: surveillance strategy for endolymphatic sac tumors.

PURPOSE: : Up to 16% of patients with the hereditary von Hippel-Lindau disease develop endolymphatic sac tumors of the inner ear. Early diagnosis and treatment of endolymphatic sac tumors can prevent audiovestibular morbidity, but optimal endolymphatic sac tumor surveillance strategy has yet to be determined. We aimed to evaluate endolymphatic sac tumor surveillance to determine the best surveillance strategy. METHODS: : In a national prospective study, 40 VHL mutation carriers were interviewed about audiovestibular symptoms and had audiological examinations and magnetic resonance imaging of the inner ear. Further, we performed a meta-analysis including all reported endolymphatic sac tumor von Hippel-Lindau disease cases in the literature (N = 140 with 156 endolymphatic sac tumors). RESULTS: : In the prospective study, endolymphatic sac tumors were suspected based on audiovestibular symptoms, audiometry, and magnetic resonance imaging in 34%, 30%, and 12.5% of subjects, respectively. In total, more than 90% of radiologically diagnosed endolymphatic sac tumors were associated with abnormal audiometric findings. No endolymphatic sac tumor genotype-phenotype correlations were found. CONCLUSION: : We recommend annual audiometry as a first-line endolymphatic sac tumor screening tool, and in countries where periodic surveillance magnetic resonance imaging of the central nervous system is performed, specific images of the inner ear should be included. Audiometric abnormalities in patients with von Hippel-Lindau disease without magnetic resonance imaging-visible endolymphatic sac tumors could be due to microscopic endolymphatic sac tumors. Determination of audiometric endolymphatic sac tumor characteristics could further target screening and improve endolymphatic sac tumor diagnosis.

Management of von Hippel-Lindau disease-associated CNS lesions.

Patients with von Hippel-Lindau disease (VHL) often harbor significant disease burden within the CNS, specifically craniospinal-axis hemangioblastomas and endolymphatic sac tumors (ELSTs). The majority (60-80%) of patients with VHL harbor hemangioblastomas, and 10-15% will develop ELSTs. Advances in the understanding of the natural history and outcomes associated with the surgical management of VHL-associated tumors have led to improved management of patients with VHL. Optimizing indications for surgical intervention and refining of surgical techniques for these lesions can reduce patient morbidity associated with the management of this syndrome. In this article, we review the various aspects of perioperative management of patients with VHL, surgical indications and general operative principles for the management of hemangioblastomas and ELSTs, and outcomes associated with the surgical treatment of these tumors.

Induced endolymphatic flow from the endolymphatic sac to the cochlea in Ménière's disease.

OBJECTIVE: The aim of the present study was to verify whether drugs injected into the endolymphatic sac (ES) can reach the cochlea and possibly treat inner ear disorders. STUDY DESIGN: Prospective cohort study. SETTING: Tertiary referral center, Otolaryngology Department, University of Verona. SUBJECTS AND METHODS: Patients with Ménière's disease (MD) who were candidates for ES decompression were selected. Nineteen subjects received dexamethasone (DEX) via injection into the ES. To objectively define whether substances administered into the ES could reach the cochlea, we added gadolinium (GD) in three patients. All subjects had intraoperative electrocorticogram recordings and an audiologic follow-up. The three subjects who underwent injection of the DEX-GD solution were followed-up with magnetic resonance imaging. The audiological data are presented during a follow-up period of 12 months. RESULTS: Intraoperative electrocochleography recordings revealed no changes in two patients and summating potentials and compound action potential latency and wave-form modifications in all the other subjects. GD distribution was observed from 48 hours to one week after ES injection into the cochlea of the three subjects injected with DEX-GD. GD-related enhancement of inner ear structures lasted more than two weeks in all subjects. Pure tone average results showed hearing improvement of at least 20 dB HL in 42 percent of patients (8 of 19) at the 12-month follow-up. Statistically significant differences emerged between the mean pure tone average of the ES procedure subjects at one and 12 months after surgery (P = 0.0096). CONCLUSION: This novel approach might reveal new prospects for treating viral, metabolic, autoimmune, and genetic disorders of the cochlea.

Analysis of hearing preservation after endolymphatic mastoid sac surgery for Meniere's disease.

OBJECTIVES/HYPOTHESIS: Comparison of audiometric outcomes between patients with definite Meniere's disease who underwent endolymphatic mastoid sac surgery (EMSS) following failed medical therapy and patients who underwent medical therapy only. STUDY DESIGN: Retrospective chart review of 456 consecutive patients between 1997 and 2006. METHODS: Outcome measures were changes in pure-tone average (PTA), word recognition score (WRS), and speech reception threshold (SRT). RESULTS: Of 58 qualified patients, 29 who underwent EMSS after failing medical therapy showed a 4 dB decrease in PTA, a 2% increase in WRS, and a 2 dB decrease in SRT. Twenty-nine patients treated with medical therapy only demonstrated a 1 dB PTA increase, 2% WRS improvement, and 2 dB SRT improvement. No significant difference was noted between the medically and surgically managed patients in terms of changes in PTA (P = .34) or WRS (P = .95) after treatment. Of all patients in the study, 60% had no clinically significant change in hearing, whereas 24% improved and 16% worsened. The distribution of post-treatment hearing changes between the medical and surgical groups was statistically insignificant (P = .17). CONCLUSIONS: The changes in PTA and WRS among patients with Meniere's disease managed with medical therapy or EMSS were not statistically significant. Although performing EMSS to treat the vertigo of Meniere's disease does not appear to be associated with an increased risk of deteriorating auditory function after treatment, surgery also does not confer an increased likelihood of stabilizing or improving hearing.

Antisecretory factor-inducing therapy improves the clinical outcome in patients with Ménière's disease.

CONCLUSION: Intake of antisecretory factor (AF)-inducing SPC-flakes significantly reduced vertigo in patients suffering from Ménière's disease (MD). The positive effect may be due to a modulation of the transport of water and ions in the endolymphatic space. OBJECTIVE: To evaluate the effects of a 3-month treatment period with SPC-flakes in patients suffering from MD. PATIENTS AND METHODS: A prospective, double-blind, placebo-controlled study was performed. A total of 51 adult patients with MD were included in the study: 27 subjects treated with SPC-flakes and 24 subjects with control cereals. The patients received SPC-flakes or control cereals (1 g per kg body weight per 24 h in two servings) for 3 months. Otoneurological examinations were carried out before and after this period. RESULTS: The severity of MD was classified according to the American Academy of Otolaryngology-Head and Neck Surgery (AAO-HNS) grading system. Fourteen of the 27 patients randomized to intake of the AF-inducing SPC-flakes reported decreased vertigo, compared with 2 of 24 in the control group (p < 0.001). No consistent change in the otoneurological examinations could be demonstrated in any of the groups of patients.

A new animal model for Ménière's disease.

CONCLUSION: A new murine model for the study of Ménière's disease has been developed by treatment with both lipopolysaccharide (LPS) and aldosterone. Induction of vestibular dysfunction in the hydropic animal model may entail additional stress such as reduced inner ear blood flow, and sudden acute changes in endolymph volume and/or pressure. OBJECTIVE: The purpose of this study was to develop a more suitable animal model, showing closer resemblance to the pathophysiological process in Ménière's disease. MATERIALS AND METHODS: Adult CBA/J mice were treated by intratympanic injection of LPS, intraperitoneal injection of aldosterone, or injection of both LPS and aldosterone. Morphological analyses were performed in the cochlea and endolymphatic sac. RESULTS: All experimental animals showed mild to moderate endolymphatic hydrops. Those treated with both LPS and aldosterone showed reversible vestibular dysfunction after the intratympanic injection of epinephrine.

Endolymphatic sac decompression as a treatment for Meniere's disease.

OBJECTIVES/HYPOTHESIS: Endolymphatic sac decompression is a surgical treatment option for patients with medically intractable Meniere's disease. However, effectiveness is debated because published data show great variability. Outcome-based research studies are useful in incorporating the patient's perspective on the success of treatment. To further assess effectiveness of endolymphatic sac decompression, we performed a prospective study to examine both symptom-specific and general health outcomes. STUDY DESIGN: Prospective, observational outcome study. METHODS: Nineteen patients with endolymphatic sac decompression responded to symptom-specific questionnaires and the Medical Outcomes Short-Form 36 Health Survey (SF-36) before and after surgery. Follow-up ranged from 6 to 58 months with a mean duration of 50 months. RESULTS: Overall measures of physical health were significantly improved following endolymphatic sac decompression (P = .04), whereas overall measures of mental health were unchanged (P = .74). Role Physical and Social Functioning scores were significantly improved following endolymphatic sac decompression (P = .04 and P = .03, respectively). Study patients scored significantly lower (P < .05) than SF-36 normative data in 6 of 10 categories before endolymphatic sac decompression but patient scores were not significantly different from normal scores in all but one category (General Health) following endolymphatic sac decompression. The mean number of vertigo episodes was significantly reduced from an average of 8.3 times per month to an average of 2.6 times per month following endolymphatic sac decompression (P = .006). Ninety-five percent of patients (18 of 19 patients) reported improvement in symptoms (frequency, duration, or intensity) of vertigo and 37% (7 of 19 patients) reported complete resolution of vertigo. CONCLUSION: Endolymphatic sac decompression significantly improved perception of physical health, as well as symptom-specific outcomes, in patients with medically intractable Meniere's disease.

Local overpressure treatment reduces vestibular symptoms in patients with Meniere's disease: a clinical, randomized, multicenter, double-blind, placebo-controlled study.

OBJECTIVES: To evaluate the efficacy of a new device, the Meniett, in the treatment of Meniere's disease. The device delivers pressure pulses to the middle ear through a ventilating tube in the tympanic membrane at a frequency of 6 Hz for 0.6 second. After rising to a pressure level of 1.2 kPa, the pressure oscillates between 0.4 and 1.2 kPa. It is believed that the pressure changes are conveyed to the inner ear, inducing a transport of fluids via the pressure outlets and thus reducing the endolymphatic hydrops. STUDY DESIGN: A clinical, randomized, multicenter, double-blind, placebo-controlled study. A total of 40 patients were included that had active Meniere's disease according to American Academy of Otolaryngology-Head and Neck Surgery criteria, aged between 20 and 65 years, with a history of at least eight attacks during the past year. After insertion of the ventilation tube, the patients should have had attacks of vertigo for 2 months before entering the study. OUTCOME MEASURES: Primary study endpoints were change in frequency of vertigo, change of functionality profile, and change in patient perception of vertigo (visual analogue scale); secondary endpoints were perception of tinnitus, aural pressure, and hearing, as well as an audiologic evaluation of hearing before and after the treatment period. RESULTS: The functionality level improved statistically significantly in the active group compared with the placebo group (p=0.0014), as did the visual analogue scale evaluation of vertigo (p=0.005). There was a trend toward a reduction of the frequency of vertiginous attacks that was not significant (p=0.090). With regard to the secondary endpoints, there was no statistical difference between active and placebo groups. CONCLUSION: Local overpressure treatment is a novel treatment that is noninvasive, nondestructive, and safe. It significantly reduces vestibular symptoms in patients with Meniere's disease. The Meniett was cleared by the Food and Drug Administration in 2000.

Measurement of the endolymphatic sac potential in human.

In this study, we measured human endolymphatic sac potential (ESP) in 8 patients with vestibular schwannoma and in five patients with Ménière's disease during surgery. ESP was measured with a glass electrode filled with 154 mM NaCl and with an outside tip diameter ranging from 2 to 3 microm. The mean value of human ESP in patients with vestibular schwannoma was +13.3+/-1.9 mV. Since electron microscopy showed that the endolymphatic sacs of the eight patients with vestibular schwannoma were normal in the ultrastructures the value can be close to normal human ESP. While in Ménière's disease, three cases showed low potentials and two cases showed almost the same values observed as in the eight patients with vestibular schwannoma. In the two cases with Ménière's disease, the epithelial cells of the endolymphatic sac were preserved. Our study can be considered as the first successful measurement of human ESP and revealed the existence of Ménière's disease having normal endolymphatic sac in function as well as morphology.

Endolymphatic sac surgery for Meniere's disease: experience with over 3000 cases.

The foregoing discussion has attempted to substantiate and clarify the six propositions outlined at the outset in light of the author's personal experience. In sum, the following points are emphasized: Employment of ESS for treatment of intractable Meniere's disease in cases where the sac is definitively delineated, the real sac lumen entered, the sac's integrity preserved, and sac enlargement technique is employed has an approximate 90% chance of achieving complete or substantial control of vertigo in the short run (2-3 years). Although there seems to be little likelihood of pushing the short-term rate of vertigo control obtainable with ESS significantly beyond the 90% mark, there is still room for improvement of longer-term control of Meniere's disease symptoms, either through modification of surgical procedure or, as the author recommends, through treatment at an early stage of the disease. The efficacy of ESS almost certainly has a definite, although presently ill-understood, pathophysiologic basis and cannot be purely attributable to a placebo effect. Regardless of limitations and uncertainties surrounding Meniere's disease and treatment of it, ESS is indisputably both safe and highly effective and, in the author's opinion, continues to be the preferred treatment for medically refractory Meniere's symptom-complex.

Intratympanic gentamicin therapy for persistent vertigo after endolymphatic sac surgery.

OBJECTIVES: To evaluate the role of intratympanic gentamycin therapy (ITGM) in controlling vertigo in patients with refractory Meniere's who have recurrent or persistent vertigo after endolymphatic sac surgery. STUDY DESIGN AND SETTING: A retrospective review of 491 patients seen in a university balance clinic between July 1999 and July 2000. Of these, 68 patients had Meniere's disease; 4 patients had recurrent vertigo after endolymphatic sac surgery and were followed for at least 1 year. These 4 patients received a series of ITGM injections. Outcome measures included control of vertigo and audiometric results. RESULTS: Three of 4 (75%) patients had control of their vertigo with ITGM therapy. The 1 patient who failed ITGM therapy underwent a successful vestibular neurectomy with ultimate control of his vertigo. No patients had progression of their sensorineural hearing loss. CONCLUSION: ITGM therapy can be used to control vertigo in selected patients with Meniere's disease who have persistent vertigo after unsuccessful endolymphatic sac surgery. SIGNIFICANCE: ITGM therapy may reduce the need for vestibular neurectomy in patients with refractory Meniere's disease after endolymphatic sac surgery.

Ultrastructure of the endolymphatic sac in two-phase endolymphatic hydrops in the guinea pig.

Two-phase endolymphatic hydrops is a subtle experimental model for Meniere's disease. Chronic dysfunction of the endolymphatic sac, induced by dissection of the most distal part without causing damage to the intermediate part, is combined with increased endolymph production induced by administration of aldosterone which stimulates the N/K-ATPase in the stria vascularis. A transmission electron microscopic study was performed on the endolymphatic sacs of four groups of guinea pig cochleas: controls: non-operated aldosterone-treated cochleas; operated (dissection of the endolymphatic sac) cochleas; operated and aldosterone-treated cochleas. Light and electron microscopy showed a normal morphology in the controls. Aldosterone treatment had no visible effect. Dissected ears revealed severe deviations. The epithelium of the intermediate sac was low, showed dilated lateral intercellular spaces indicating elevated fluid transport and displayed serious degenerative processes. Distally, the endolymphatic sac was completely blocked by newly formed bone. Additional aldosterone treatment had no cumulative effect on the dissected ears.

Effect of locally applied drugs on the endolymphatic sac potential.

In Ménière's disease, an inner ear disorder related to an endolymphatic hydrops, an alteration of the functioning of the endolymphatic sac has been proposed. The endolymphatic sac is assumed to be involved in the secretion/resorption of endolymph. The epithelial transport systems have been indirectly studied by the recording of the endolymphatic sac transepithelial potential (ESP) in control conditions and after the local injection of drugs such as diuretics that have been proposed in the treatment of Ménière's disease. The ESP was recorded, in vivo, in guinea pigs up to 150 minutes after the perisaccular injection of 5 microL of a 150 mmol/L (mM) NaCl solution containing various drugs known to inhibit ionic transport systems. The initial ESP was +8.4+/-0.3 mV (mean +/- SEM, n = 78). The basolateral injection of 5 microL of 150 mM NaCl induced an ESP decrease of 64%+/-6.0% (n = 12), 5 minutes after the end of the injection. Then ESP increased, returning to its initial value at 60 minutes and surpassing it at 120 minutes. Diuretics such as acetazolamide (10[-3] mol/L [M]), an inhibitor of carbonic anhydrase, and amiloride (10[-4] M), an inhibitor of Na channel or Na/H exchanger, decreased the ESP recovery. At variance, bumetanide (10[-6] M, 10[-4] M), the Na-K-Cl cotransport inhibitor, and chlorothiazide (10[-4] M), a Na-Cl cotransporter inhibitor, failed to alter the ESP as compared with the control group. Ouabain (10[-3] M), the Na+,K+-adenosine triphosphatase (ATPase) inhibitor, prevented the ESP recovery otherwise observed 60 minutes after the NaCl injection. Bafilomycin A1, the inhibitor of the vacuolar-type H+-ATPase, prevented the recovery of the ESP with a log-dose/effect (10[-5] M, 10[-6] M, 10[-8] M). Disulfonic acid stilbene (DIDS) (10[-4] M), an inhibitor of transporters involving HCO3-, also prevented the ESP recovery. These results suggest that the genesis of the ESP was highly dependent on acid-base transport systems including carbonic anhydrase, a vacuolar-type H+-ATPase, and an anionic transport system blocked by DIDS. Further studies are needed to confirm the alteration of the acid-base balance in this epithelium and its possible involvement in the pathogenesis of Ménière's disease.