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PubMed1979

Fluid motion in the mammalian organ of Corti. A possible source of the second filter.

A mechanical analysis of the functioning of the mammalian organ of Corti as deduced from experimental observations and electronmicroscopic studies of the organ has been conducted. It was found that the arch of Corti is responsible for initiating a fluid motion in the spiral sulcus and reticular lamina which could stimulate the inner hair cells. A three-dimensional linear mathematical model with no arbitrary parameters is proposed to describe the force acting on the inner hair cell cilia as a function of arch displacement. Analysis of the model results show that the model (a) correctly predicts the form of the neural response for a low frequency square wave of arch motion, (b) demonstrates a physiologically reasonable time constant of 245 musec, (c) shows a sharpening of neural stimulation of physiological importance, (d) can explain the qualitative difference of neural responses to arch motions of opposite polarity, (e) demonstrates a phase difference between outer and inner hair cell stimulation, and (f) appears to be chemically and metabolically vulnerable.

Animals↗
PubMed2004

Do forward- and backward-traveling waves occur within the cochlea? Countering the critique of Nobili et al.

The question of whether or not forward- and backward-traveling waves occur within the cochlea constitutes a long-standing controversy in cochlear mechanics recently brought to the fore by the problem of understanding otoacoustic emissions. Nobili and colleagues articulate the opposition to the traveling-wave viewpoint by arguing that wave-equation formulations of cochlear mechanics fundamentally misrepresent the hydrodynamics of the cochlea [e.g., Nobili et al. (2003) J. Assoc. Res. Otolaryngol. 4:478-494]. To correct the perceived deficiencies of the wave-equation formulation, Nobili et al. advocate an apparently altogether different approach to cochlear modeling--the so-called "hydrodynamic" or "Green's function" approach--in which cochlear responses are represented not as forward- and backward-traveling waves but as weighted sums of the motions of individual basilar membrane oscillators, each interacting with the others via forces communicated instantaneously through the cochlear fluids. In this article, we examine Nobili and colleagues' arguments and conclusions while attempting to clarify the broader issues at stake. We demonstrate that the one-dimensional wave-equation formulation of cochlear hydrodynamics does not misrepresent long-range fluid coupling in the cochlea, as claimed. Indeed, we show that the long-range component of Nobili et al.'s three-dimensional force propagator is identical to the hydrodynamic Green's function representing a one-dimensional tapered transmission line. Furthermore, simulations that Nobili et al. use to discredit wave-equation formulations of cochlear mechanics (i.e., cochlear responses to excitation at a point along the basilar membrane) are readily reproduced and interpreted using a simple superposition of forward- and backward-traveling waves. Nobili and coworkers' critique of wave-equation formulations of cochlear mechanics thus appears to be without compelling foundation. Although the traveling-wave and hydrodynamic formulations impose strikingly disparate conceptual and computational frameworks, the two approaches ultimately describe the same underlying physics.

Animals↗
PubMedDate not supplied

Hyaluronan content in human inner ear fluids.

Histochemical analyses of the luminal contents of the endolymphatic sac in numerous mammalian species have indicated a presence of acid mucopolysaccharides or proteoglycans. In the present study, one of these substances, hyaluronan (hyaluronic acid; HA), in endolymphatic sac endolymph and vestibular perilymph in humans, was biochemically determined with a highly specific radioassay. A considerable variation in HA concentration was noted between the individual ES endolymph samples, with a mean value of 2.50 micrograms/g (range 0.00-10.86). In perilymph the HA concentrations were less variable and the mean concentration was 0.91 micrograms/g (range 0.56-1.51). The difference between endolymph and perilymph HA concentration was not statistically significant (p greater than 0.05). The ability of HA to interact with proteoglycans, thereby forming giant hydrophilic molecules, could be important for ES function. These molecules may create a swelling pressure which is resistant to compressive forces that under conditions of increased intracranial hydrostatic pressure otherwise could cause ES collapse and impaired function.

Adult↗
PubMed1973

The mutual independence of the endolymphatic potential and the concentrations of sodium and potassium in endolymph.

The relationship between the endolymphatic potential (EP) and the sodium and potassium concentration gradients between endolymph and interstitial fluid was studied both by measuring the EP at varying concentrations of sodium and potassium in endolymph and by measuring the effect of a depressed EP on the concentrations of these cations. Ethacrynic acid was used in dogs to change the concentration of sodium and potassium (meq/liter) in endolymph from 5.8 and 148 to 134 and 24.3, respectively. No change in the EP accompanied these alterations. In a second series of experiments the EP was reduced from + 72 mV to + 31 mV for a mean duration of 20 min. No change in the concentration of sodium and potassium in endolymph was found during the period of reduced EP. These data suggest that there is little relationship between the EP and the sodium and potassium concentrations in endolymph.

Animals↗
PubMed1984

Inter- and intracompartmental osmotic gradients within the rat cochlea.

The osmolality and the electrochemical composition of the endolymph, a potassium-rich positively polarized extracellular fluid in the cochlea, was studied in the rat. Endolymph of each cochlear turn was hyperosmotic to perilymph and plasma. Osmolalities (mosmol/kg H2O) were 329 +/- 2.9 (mean +/- SE) (n = 13) in basal turn endolymph, 322 +/- 2.7 (n = 9) in middle turn endolymph, 317 +/- 5.2 (n = 3) in apical turn endolymph, 289 +/- 3.1 (n = 14) in perilymph of the scala vestibuli, and 298 +/- 1.8 (n = 7) in plasma. Moreover, differences in osmolality and electrochemical composition of endolymph, involving resting potential and K and Cl concentrations, were observed between the basal and the middle cochlear turns, suggesting the presence of an electrical and osmotic gradient within endolymph, declining from the base to the apex of the cochlea. The active potassium transport into endolymph, located presumably in the stria vascularis, could account for both the internal and external osmotic gradients.

Animals↗
PubMed1987

Early effects of acetazolamide on anionic activities of the guinea pig endolymph: evidence for active function of carbonic anhydrase in the cochlea.

The effect of acetazolamide (ACZ) on HCO3- and Cl- activities in inner ear fluid was investigated by ion-selective microelectrode methods. The endocochlear potential, at 81.6 +/- 1.5 mV under normal conditions, was reduced by 4.9 +/- 0.9 mV in 30 min following the ACZ injection. The HCO3- concentrations by 11.5 +/- 1.7 mM in 30 min, while the change of Cl- level was not consistent but showed a tendency toward slight increase in average. The calculated PCO2 in endolymph was 39.6 mmHg. ACZ induced a constant elevation of the endolymph PCO2, with an increase in the venous PCO2 during the initial 20 min and thereafter the endolymph PCO2 attained a plateau despite the continuous increase of the venous PCO2. We postulate that the HCO3- secretion into the endolymph is mediated by carbonic anhydrase (CAH) and is decreased by ACZ due to the inhibition of CAH.

Acetazolamide↗
PubMed1981

Pharmacokinetics of gentamicin in perilymph and endolymph of the rat as determined by radioimmunoassay.

The kinetics of gentamicin in the inner ear fluids of the rat were studied with a sensitive radioimmunoassay. Continuous infusion over a broad range (7.5--150 micrograms/min) was used to obtain equilibrium. The lowest rate of infusion produced plasma concentrations after 45 min that were within the range of peak serum levels desirable in humans. The purity of perilymph and endolymph was ensured by measurement of sodium and potassium concentrations. The concentration of gentamicin in perilymph was linearly related to its concentration in plasma, which depended on the rate of infusion. After six days of constant infusion of gentamicin at 15 microgram/min, the concentrations in plasma, perilymph, and endolymph averaged 25.8, 5.1, and 1.2 micrograms/ml, respectively, for five of 11 rats. Gentamicin cleared from the perilymph with a half-life of 3 hr.

Animals↗
PubMedDate not supplied

The preparation of acetic acid for use in otic drops and its effect on endocochlear potential and pH in inner ear fluid.

The ototoxicity of an otic drop preparation containing 2% acetic acid and 3% propylene glycol (VoSol, Denver Chemical Co., Humacao, PR) was investigated according to measurements of endocochlear potential (EP) and inner ear fluid pH. The application of this preparation to the round window membrane for 30 minutes caused a depression in EP from 80.5 +/- 2.5 mV (mean +/- SD; n = 6) to 11.7 +/- 7.7 mV, and lowered inner ear fluid pH from 7.55 +/- 0.09 to 5.06 +/- 0.19 (n = 6) in perilymph and from 7.52 +/- 0.07 to 5.88 +/- 0.63 (n = 6) in endolymph. Two percent acetic acid produced similar changes after 30 minutes: EP was reduced from 83.0 +/- 2.2 mV to 34.0 +/- 2.9 mV and endolymphatic pH from 7.49 +/- 0.04 to 6.83 +/- 0.21 (n = 4). However, the application of artificial perilymph of pH 4 titrated with HCl induced no significant changes in either EP or endolymphatic pH. We suggest that the mechanisms of ototoxicity in the otic drop preparation are Na+ and K+-ATPase inhibition, and that such inhibition is due to the intracellular acidification of strial cells resulting from the penetration of acetic acid across the cell membrane, and to the direct and synergistic actions of propylene glycol.

Acetates↗
PubMed1999

Salt-load electrocochleography.

OBJECTIVE: To introduce a new protocol for diagnostic electrocochleography using a pretest oral salt load to improve test sensitivity in patients with suspected inner ear fluid imbalance. STUDY DESIGN: A retrospective review of patients who reported vertigo that, by medical history, was suggestive of an inner ear fluid imbalance was preformed. The patients received a complete audiovestibular evaluation that included a baseline electrocochleogram. Despite the incapacitating nature of their vertigo, there were no symptoms or electrophysiologic abnormalities that would isolate an etiologic ear. After the baseline studies, the patients received 4 g of sodium chloride daily for 3 days before repeat electrocochleography. A control group of 13 healthy volunteers with normal baseline electrocochleography and pure tone audiometry was tested under similar conditions. SETTING: This study was conducted at an ambulatory care clinic associated with a tertiary referral medical center. INTERVENTION: Electrocochleography was performed using alternating polarity clicks presented at a rate of 9.7/sec at 95 dB nHL by an extratympanic TIPtrode electrode and recorded with a Nicolet Spirit (Nicolet Instrument Corp., Madison, WI, U.S.A.). Responses were averaged for 1000 sweeps using a 10-msec time base with bandpass filtering from 5 to 1500 Hz. A summating potential/action potential (SP/AP) ratio of 0.37 was considered the upper limit of normal. MAIN OUTCOME MEASURES: Enhancement in the SP/AP ratio from a normal baseline value to > 0.37 after oral salt loading was indicative of a positive test. RESULTS: None of the ears from control subjects had a positive salt load electrocochleogram, and one or both ears in 38% of the patients in the study group with normal baseline SP/AP ratios and symptoms of inner ear fluid imbalance converted to abnormal. The mean SP/AP ratio of the control group for the conditions before and after salt-load was not statistically different (p = 0.48), although the difference in the mean SP/AP ratio in the study group after salt loading was statistically significant (p = 1.329 x 10(-5)). CONCLUSIONS: A group of patients who reported vertigo with no localizing abnormalities had a statistically significant increase in the mean SP/AP ratio after ingestion of a large quantity of sodium chloride. A modest percentage had elevation of the SP/AP ratio above the upper limit of normal for our audiovestibular lab. The localization of a "salt-senstitive" ear could assist the clinician in the management of these difficult problems with long-term medical therapy or surgical treatment when alternative measures fail.

Adolescent↗
PubMed1983

Energy dispersive x-ray analysis of inner ear fluids and tissues during the ontogeny of cochlear function.

Energy dispersive x-ray analysis (EDXA) was used to characterize freeze-dried, microdissected samples of inner ear fluids and tissues from neonatal gerbils throughout the period of cochlear functional development, between 10 and 18 days after birth. EDXA spectra from endolymph residue demonstrated that the adult ionic composition of this fluid is established before functional onset, and before the appearance of the endocochlear potential. However, stria vascularis spectra showed substantial increases in relative phosphorus and sodium content during the period in which auditory thresholds improve by approximately 100 dB, in which the endocochlear potential appears and increases to its adult value, and in which the level of metabolism of the stria increases dramatically. The increase in relative phosphorus content of stria in particular occurred with a time course which was very similar to, though slightly earlier than, that of the developmental increase in the endocochlear potential. It is concluded that increases in the relative phosphorus content of stria may represent increases in inorganic phosphate associated with strial metabolism. Increases in relative sodium content may reflect the action of an ion transport system which directs this element into strial cells during generation of the endocochlear potential.

Aging↗
PubMedDate not supplied

Electrochemical composition of the cochlear fluids in the early experimental hydrops. Preliminary results.

The composition of endolymph and perilymph was studied in the guinea pig cochlea after 2 and 6 weeks of blockage of the vestibular aqueduct in an experimental model of hydrops. Compound action potential was monitored several times in the observation period. The endocochlear potential was measured and the endolymph was sampled at the first and third turns of the scala media. The Na, K, and Cl concentrations were determined in nanolitre aliquots of endolymph and of perilymph, the latter sampled from the basal scala vestibuli. After 2 weeks, no change in endolymphatic electrochemical composition was observed. After 6 weeks, endocochlear potential was decreased by 25% at both cochlear turns; K concentration was decreased in endolymph of the basal turn and Cl concentration was decreased in both turns; the calculated osmolality (Na + K + Cl) was decreased in both turns. These results indicate that the blockage of the vestibular aqueduct induced early auditory dysfunction whereas alterations of the electrochemical composition of endolymph occurred later after a time lag of more than 2 and less than 6 weeks.

Action Potentials↗
PubMed1981

[Lactate and pyruvate concentrations in perilymph, blood, and cerebrospinal fluid of guinea pigs].

Lactate and pyruvate were studied comparatively in perilymph (PL), blood, and cerebrospinal fluid (CSF) of anesthetized guinea pigs. Arterial blood pressure, heart and respiration rate (Fig. 1), and arterial blood-gas state (Table 2) were simultaneously checked in a group of the animals. The metabolites were determined enzymatically by using the fluorometric technique. The studies have shown (Table 1) that both the lactate and the pyruvate concentrations are in PL at a similar rate (about 3:1) higher than in native blood and also higher than in CSF. The metabolite values of blood, especially the lactate values, were lower when blood was taken alone, e.g., more physiological, than in the case when CSF and PL had been sampled before. The lactate/pyruvate ratios of Pl are somewhat higher than the blood ratios. The ratio of CSF was found to be lower. The high metabolite levels in PL suggest an intracochlear origin. A direct perilymphatic lactate origin could not be detected.

Animals↗
PubMedDate not supplied

Elemental composition of the developing inner ear.

The elemental composition of the inner ear fluid-filled compartments has been analyzed using the x-ray energy dispersive technique (CBA mouse). Special attention has been focused on the maturation of endolymph. A few days before and after birth the relative peak intensity of potassium (RK) in the vestibular endolymphatic compartment was slightly surpassing that in the cochlear part of the labyrinth. From the fourth day after birth (DAB) a rapid increase occurred concerning the RK. The highest RK was found in the endolymphatic space in the basal part of the cochlea followed by that in the vestibular endolymph. The lowest RK was measured in endolymph of the apical part of the cochlea. These obvious differences were abandoned already on the sixth DAB. A mature composition of endolymph was reached on the eighth DAB. The present technique does not allow analyses of differences between cochlear and vestibular endolymph with regard to minimal shifts.

Animals↗
PubMed2005

Determinants of spatial and temporal coding by semicircular canal afferents.

The vestibular semicircular canals are internal sensors that signal the magnitude, direction, and temporal properties of angular head motion. Fluid mechanics within the 3-canal labyrinth code the direction of movement and integrate angular acceleration stimuli over time. Directional coding is accomplished by decomposition of complex angular accelerations into 3 biomechanical components-one component exciting each of the 3 ampullary organs and associated afferent nerve bundles separately. For low-frequency angular motion stimuli, fluid displacement within each canal is proportional to angular acceleration. At higher frequencies, above the lower corner frequency, real-time integration is accomplished by viscous forces arising from the movement of fluid within the slender lumen of each canal. This results in angular velocity sensitive fluid displacements. Reflecting this, a subset of afferent fibers indeed report angular acceleration to the brain for low frequencies of head movement and report angular velocity for higher frequencies. However, a substantial number of afferent fibers also report angular acceleration, or a signal between acceleration and velocity, even at frequencies where the endolymph displacement is known to follow angular head velocity. These non-velocity-sensitive afferent signals cannot be attributed to canal biomechanics alone. The responses of non-velocity-sensitive cells include a mathematical differentiation (first-order or fractional) imparted by hair-cell and/or afferent complexes. This mathematical differentiation from velocity to acceleration cannot be attributed to hair cell ionic currents, but occurs as a result of the dynamics of synaptic transmission between hair cells and their primary afferent fibers. The evidence for this conclusion is reviewed below.

Afferent Pathways↗
PubMed1984

Electrochemical heterogeneity of the cochlear endolymph: effect of acetazolamide.

The electrochemical composition of endolymph (EL) of two adjacent cochlear turns was studied in anesthetized rats. Differences in [K]EL, [Cl]EL, and endocochlear potential (EP) were found between the basal turn (165.6 +/- 3.0 mM, n = 14; 144.6 +/- 2.1 mM, n = 14;96.6 +/- 1.9 mV, n = 5, respectively) and the middle turn (155.7 +/- 2.5 mM, n = 15; 133.2 +/- 1.5 mM, n = 15; 87.0 +/- 1.6 mV, n = 6, respectively). The pH values of inner ear fluids were evaluated with 5,5-dimethyloxazolidine-2,4-dione: EL pH of either turn was not different from blood and perilymph (PL) pH. Acetazolamide (40 mg X kg body wt-1) reduced EP and [Cl]EL at each turn by about 20 and 6%, respectively, but [K]EL was unchanged. The electrochemical differences between the two turns persisted. Acetazolamide produced a 0.2-unit decrease in blood pH while the pH values of EL and PL remained unchanged. These results suggest the existence of an electrochemical gradient within EL from the base to the apex of the cochlea involving K+ and Cl- concentrations. H+ and HCO-3 do not appear to participate in this gradient, and the acid-base status in EL could be maintained both by active H+ transport into EL and by HCO-3 formation in the cochlear epithelium.

Acetazolamide↗
PubMed1978

The effects of ethacrynic acid upon the potassium concentration in guinea pig cochlear fluids.

After i.v. injection of 50 mg/kg ethacrynic acid (EA), potassium concentration in the endolymph (Ke+) measured with K+-specific microelectrodes decreases by 10 mM at the most and endocochlear potential falls to negative values. Potassium concentration in the perilymph (Kp+) generally does not change, but sometimes a transient decrease in Kp+ level of about 0.5 mM was observed, presumably due to the electrogenic effect of the time-related decrease of the endocochlear potential. When anoxia is induced approximately 120 min after EA administration Ke+ slowly decreases. The decrease in Ke+ 50 min after the arrest of ventilation is smaller when compared with the Ke+ anoxic decrease without preceding EA administration. The endocochlear potential, which falls to negative values during anoxia after EA administration, does not return to the zero level as in the case when only anoxia is applied. Similarly, during anoxia, which follows EA administration, the perilymphatic Ke+ concentration increases more slowly than in the case when only anoxia is introduced. It is assumed from the results that EA abolishes activity of the positive electrogenic K+ pump and reduces the passive permeability of the walls of the cochlear duct to the potassium ions.

Animals↗
PubMed1988

Chronic perilymphatic fistula: experimental model in the guinea pig.

Chronic perilymphatic fistulas were created in guinea pig cochleas using silicone rubber tubing placed into the scala tympani through the round window. Fistula patency was determined by fluorescein perfusion into cerebral spinal fluid. Fistula were found to be patent in 6 of 6 animals at 7 days and 8 of 13 animals at 28 days. Analysis of ABRs revealed threshold increases of 10 to 15 dB across all frequencies at 1 hour and 7 days. However, thresholds returned to pre-fistula levels by 28 days. Animals with acute fistulas (simple laceration of the round window) had similar threshold increases at 1 hour; however, recovery to baseline levels occurred by day 7. Control animals with intact round windows did not have threshold shifts. Scanning electron microscopy revealed hair cell loss localized to the apical and basal turns of the cochlea. The morphologic changes observed occurred acutely (within 7 days) and were not progressive, despite the presence of a fistula. Hair cell loss or degeneration did not correlate with hearing loss.

Animals↗
PubMed1991

Ionic activities of the inner ear fluid and ionic permeabilities of the cochlear duct in endolymphatic hydrops of the guinea pig.

Ionic activities (K+, Na+, and Cl-) of the perilymph and endolymph of the basal turn were measured using ion-selective microelectrodes in experimentally induced endolymphatic hydrops of the guinea pig. Three months following the obstruction of the endolymphatic duct and sac, the endocochlear potential (EP) of hydroptic ears was measured at 59.7 +/- 9.6 mV (N = 12) which was significantly lower than the EP of the contralateral control ears (84.4 +/- 2.8 mV, N = 12). A paired t-test (P greater than 0.05) showed no significant differences of ion concentrations of the inner ear fluid between the hydroptic and contralateral ears. Ion permeabilities of the cochlear duct following anoxia were calculated according to the Nernst-Planck equation. Comparing hydroptic and normal ears following anoxia, a statistically significant decrease was observed in the permeability coefficients for K+. Similarly, K+ conductance was significantly lower in the hydroptic ears than in the normal ears. Total conductance of the cochlear duct, defined as the sum of each ion conductance, was 0.560 siemens in the normal ears and 0.217 siemens in the hydroptic ears. On the basis of the Goldman-Hodgkin-Katz equation, preexisting negative EP in the normal state was calculated to be -24.5 mV in normal ears and -21.4 mV in hydroptic ears. Therefore, the positive component of the EP was 108.9 mV in normal ears and 81.1 mV in hydroptic ears. These findings suggest that the pathophysiology of hydrops involves changes in K+ permeability and the inhibition of the electrogenic transport processes.

Animals↗