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Turn-specific differences in the endocochlear potential between albino and pigmented guinea pigs.

Recent findings indicate that structural differences exist in the stria vascularis (SV) between albino and pigmented guinea pigs. In the higher cochlear turns, volume density for marginal cells in the albino SV is abnormally large, while that for intermediate cells (melanocytes) is abnormally small. These anatomical variations suggest that functional differences between albino and pigmented inner ears also may be found. To examine this possibility, four strains of guinea pigs were studied, consisting of Hartley albino (N = 9) and NIH outbred pigmented (N = 15) guinea pigs, as well as albino (N = 11) and pigmented (N = 15) guinea pig siblings born to mixed litters. Tracheotomy and carotid artery cannulation were performed. Animals were mechanically ventilated, with periodic samples drawn for arterial blood gas analysis. Blood pressure, heart rate and rectal temperature were monitored. Compound action potentials were measured first to assess cochlear viability. Positive endocochlear potentials (+EP) then were recorded, beginning with the fourth turn, followed by the first, second and third turns. Results showed that the +EP in albinos remained relatively constant across cochlear turns, but decreased significantly from base to apex in the pigmented inner ears. Across all animals, mean +EPs (mV +/- S.E.M.) for turns 1-4 in albinos were: 72.5 (2.5), 68.7 (2.3), 59.2 (2.7), 68.1 (3.3); pigmented values were: 72.9 (2.9), 66.9 (2.6), 53.8 (3.0), 57.0 (2.7). One-way ANOVAs did not show a significant difference in albino +EPs between any of the cochlear turns, but did indicate a highly significant difference between turns in the pigmented inner ears (P < 0.000004). Post hoc comparisons demonstrated +EPs in turns 3 and 4 were smaller than in turn 1. Since turn 3 was recorded last in these experiments, and was reduced in value relative to turn 4 in both groups, it is likely that cochlear deterioration contributed to this result more than any other factor. These results, combined with previous anatomical data, indicate that a diminution of melanocyte cell volume in the albino SV is accompanied by an increase in marginal cell volume density and larger +EPs in the higher cochlear turns, at least at resting levels.

Albinism↗

Changes in off-lesion endocochlear potential following localized lesion in the lateral wall.

Endocochlear potential (EP) was measured at various off-lesion sites after a small focal lesion was made in the lateral wall of the guinea pig cochlea. Lesions were produced by a photochemical reaction between systemically administered rose bengal and focused green light illumination. In 21 ears, continuous measurement for 30 min after onset of the reaction at turns apical or basal to the site of illumination revealed no significant changes in EP compared with the control value (p < 0.01). In another group of 43 ears, EP was measured at 3 days post-illumination. A significant decline was seen at every site located apical to the lesion (p < 0.001). Conversely, no significant change was measured at any site located basal to the lesion. These findings suggest that the decrease in EP assumes the form of a gradient from the lower to upper turns in the guinea pig cochlea.

Analysis of Variance↗

The clinical application of acoustic distortion products.

Otoacoustic emissions provide an objective measure of hair-cell function that is independent of retrocochlear activity. Because of their frequency specificity, distortion-product emissions have great potential for clinical use. The present report describes the results of initial studies in patients with known cochlear or retrocochlear disease, diagnosed with standard otologic and audiologic tests. The cochlear group consisted of those diagnosed with noise-induced hearing loss, Meniere's disease, or hereditary hearing loss, whereas patients with acoustic neuroma comprised a retrocochlear group. A final group consisted of patients with sudden sensorineural hearing loss of unknown origin. Detailed distortion-product emission testing included the computer-controlled acquisition of "audiograms" and response/growth functions. The outcomes of these studies demonstrated that distortion-product emissions provide a noninvasive, frequency-specific test of sensory-cell function that objectively depicts the boundary between normal and abnormal hearing. These emissions were also able to effectively track dynamic changes in progressive disease processes. Finally, as a screening tool, acoustic distortion products provide an objective means of assessing cochlear status in infants and young children and in adults at risk for hearing loss. Because acoustic distortion products accurately measure the sensory component of a sensorineural hearing loss, distortion-product testing may play an important role in the diagnosis and treatment of cochlear dysfunction.

Adolescent↗

The effect of endocochlear potential suppression upon susceptibility to acoustic trauma.

In the present study we investigated the influence of decreased endocochlear potential (EP) on acoustic trauma. Guinea pigs with decreased EP following i.v. administration of furosemide (FUR) and normal EP given physiological saline solution (PSS) i.v. instead of FUR were exposed to 2 kHz pure tone ranging from 110 to 130 dB SPL for 5 min. The input-output curves of the compound action potential (CAP) before acoustic overstimulation were compared with those at 2 h after the exposure. In 125 and 130 dB SPL exposure there was no difference in threshold shift between the FUR and PSS groups. In 115 and 120 dB SPL exposure, however, the threshold shift of the FUR group was significantly smaller than that of the PSS group. There was no significant difference between the two groups in 110 dB SPL exposure. These results indicate that the threshold shift of the CAP is mainly due to excessive vibration of the basilar membrane in the greater stimulus groups (125-130 dB SPL) but that the energy exhaustion of the hair cells to a certain extent participates in the threshold shift when the stimulus is milder (115-120 dB SPL). It is concluded that susceptibility to acoustic trauma of a milder intensity (115-120 dB SPL) is reduced when the energy consumption rate of the organ of Corti is decreased by EP suppression.

Acoustic Stimulation↗

[Measurement of Ca2+ concentration and endocochlear potential in experimental endolymphatic hydrops in vivo].

This study was based on observations on 14 normal guinea pigs and 17 guinea pigs in which the left endolymphatic duct and sac had been surgically obliterated to induce endolymphatic hydrops. Three groups of hydropic animals were tested 1, 2 and 3 months after surgery. The Ca2+ concentration and endocochlear potential (EP) were recorded by means of double-barrelled ion selective micro-electrode in the third turn of the cochlea. The results indicated that a decrease in EP and an increase in Ca2+ in hydropic cochlea, a negative correlation was present. In the control ear, the values of Ca2+ and EP were 26.4 +/- 0.33 microns/L (n = 14) and 72.78 mV (n = 14), respectively; in the hydropic ear, the value of Ca/+ was 404.47 +/- 79.74 microns/L (n = 17), while the EP was 55.82 +/- 3.28 mV (n=17). According to Nerstian formula, the slope of electrochemical gradient in the control was 31 mV/decade (n = 14), but in the hydropic ear it increased to 72.5 mV/decade change in Ca2+ (n = 17). The statistical analysis showed significant difference between the control and hydropic ears. The changes were progressive and became more pronounced as the duration of hydrops prolonged. The cause of hearing loss in the Ménière's disease and the relation between the EP and CA2+ concentration had been discussed.

Animals↗

Focal damage to cochlear microcirculation measured using a non-contact laser blood flowmeter in guinea pigs.

The focal microcirculation damage induced by a photochemical reaction in the stria vascularis (SV) of the guinea pig cochlea was evaluated using a non-contact laser blood flowmeter (NCLBF) and the endocochlear potential (EP). Focal degeneration, including vascular thrombosis in the SV produced by the systemic infusion of rose bengal, and the illumination of green light in the second cochlear turn were observed with scanning and transmission electron microscopy. The NCLBF probe was placed at a position 10 mm from the cochlear surface, and the diameter of the laser light was focused to 1 mm in the green light illumination area. The change in NCLBF values induced by the loading of anoxia and administration of epinephrine agreed very well with those obtained with a conventional contact-type laser Doppler flowmeter. Significant decreases in the cochlear blood flow (CBF) (p < 0.01) and EP (p < 0.01) were observed at the site of the photochemical injury compared with the values at the non-illuminated area. CBF gradually decreased (82.0+/-7.3% at 10 min, 71.2+/-5.5% at 20 min, 64.3+/-11.2% at 30 min from the baseline, n=7), but blood pressure was stable. The EP values also decreased gradually during the first 13 min (79.9+/-3.7 mV at pre-illumination, 11.4+/-10.7 mV at 13 min, n=7). The gradual decline in the EP was comparable to the changes in the CBF. The NCLBF was useful for evaluating the haemodynamic properties of the cochlear microcirculation disorders, and this animal model is expected to be suitable for studying the pathology of focal cochlear vascular disease.

Animals↗

Electrocochleography and brainstem potentials in the diagnosis of the deaf child.

The deaf child must receive sound amplification before he reaches the age of two years. At this age the hearing threshold is best measured objectively by electrocochleography (ECochG) and auditory brainstem response (ABR) audiometry. When used correctly, both methods allow an exact threshold estimation which is informative enough for adequate hearing aid prescription. Both methods have advantages and disadvantages when used in children. The advantages of ECochG are: (a) a more exact threshold estimation and (b) strictly monaural evaluation. The advantages of ABR are: (a) ease of performance; it is not invasive and does not require general anaesthesia and (b) allows for exploration of higher levels in the auditory pathway up to the midbrain. We believe that ECochG and ABR are compatible and complementary in the diagnosis of childhood deafness. ABR could be used in first instance, while ECochG could be reserved for doubtful cases and for those who cannot be adequately sedated. Extra-audiological factors such as the availability of anaesthetists and varying hospital facilities, play a further role in determining the choice of electric response technique.

Audiometry↗

Susceptibility of the endocochlear potential to pH and osmolarity changes in the perilymph of the cochlea in the guinea pig.

The effects of artificial perilymph at various pH levels and osmolarities on the endocochlear potential (EP) were investigated in a guinea pig model. In 47 ears, the mean EP was 74.5 +/- 0.5 mV in the second turn of the cochlea before perilymphatic perfusion. The artificial perilymph with a pH ranging from 5 to 9 and tonicity less than 1.25 (osmolarity, 345 mosmol/l) did not alter the EP when testings were recorded for at least 1 h. However, after the start of a perfusion with a pH less than 4, the EP declined gradually but recovered to the pre-perfusion level rapidly when the perfusion was stopped. The artificial perilymph with a pH over 10 decreased the EP considerably but showed no recovery, even after cessation of the perfusion. Tonicity more than 1.35 (osmolarity, 372.6 mosmol/l) also decreased the EP, with this decrease paralleling further increases in the tonicity used. From these data, we have concluded that a perilymph perfusate with a pH from 5 to 9 and an osmolarity less than 350 mosmol/l can be used in animal testing without any noxious effects on the EP.

Animals↗

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↗

[Effects of submarine engine room steady noise on the compound action potential tuning curves and its relation to cochlear pathology in guinea pigs].

Compound Action Potential Tuning Curves (CAP-TC) for tone pip of 2k, 4 kHz were examined in 8 guinea pigs before and after exposure to noise with main energy centered in the range of 0.25-4.0 kHz. CAP-TC was measured with the pure tone simultaneous masking profiles. AP was evoked by tone pip with an intensity of 10 dB above threshold. Masker level producing 40% reduction in AP amplitude was used. Relations between changes in CAP-TC and AP threshold shifts and the pathology of the stereocilia of hair cells were evaluated by surface preparation and SEM observation in 13 ears. After noise exposure, animals with damaged stereocilia showed AP threshold shift of 20-50 dB, deteriorations of CAP-TC, decrease of Q10 dB value, threshold shift of characteristic frequencies (CF) and displacement of CF towards higher frequencies. It showed that stereocilia damage may affect the susceptibility and frequency selectivity of the cochlea. We consider the CAP-TC may be an useful and sensitive index for detecting physiological and pathological conditions of the cochlea.

Animals↗

Development of endocochlear potential and its negative component in mouse cochlea.

The chronological developmental processes of endocochlear potential (EP) and negative endocochlear potential (-EP) were investigated as a function of age from birth in the basal and second cochlear turns in normal ICR-strain mice. The EP of the basal turn developed between 5 and 17 days after birth (DAB). The -EP of the basal turn attained to its mature level on 11 DAB and it increased its absolute value further between 12 and 16 DAB and then, recovered to its mature level again on 20 DAB. The developmental processes of EP and -EP of the second turn followed similar courses to those of the basal turn although they were several millivolts different on each day in detail. The results suggest that the developmental processes of the +EP and the -EP are different. The time of reaching minimum -EP during anoxia were measured and the rate of EP decline were calculated on each animal. The rate of EP decline increased rapidly on 10 DAB, almost coinciding the day which EP began to increase abruptly. Although the rate of EP decline is influenced by several processes, this result showed one of the possibility that the sensitivity of the stria vascularis to hypoxia may develop parallel to the development of the EP.

Age Factors↗

Acoustic neuroma surgery: absent auditory brainstem response does not contraindicate attempted hearing preservation.

OBJECTIVE: Absence of auditory brainstem response (ABR) waveforms has been associated with a poor likelihood of hearing preservation following resection of acoustic neuromas. Our experience is reviewed for patients with absent preoperative ABR regarding hearing preservation, hearing improvement, and return of ABR. STUDY DESIGN: Retrospective review of 22 cases of acoustic neuroma resection. Nine patients with absent preoperative ABR were identified. All underwent tumor resection utilizing intraoperative cochlear nerve action potential (CNAP) monitoring. Postoperative hearing results and ABR waveforms were examined. METHODS: Charts were reviewed and tabulated for age, sex, tumor side, tumor size, preoperative and postoperative audiometric and ABR results, intraoperative monitoring results by ABR and CNAP, and surgical complications. RESULTS: Hearing preservation was achieved in seven of nine patients (78%) with absent preoperative ABR, as well as six of seven patients (86%) with tumors less than or equal to 20 mm in greatest dimension. Although intraoperative ABR monitoring was not possible in any of these patients, CNAP monitoring was successful in all. Return of ABR waveforms was observed in four of the six patients (67%) tested from 3 to 22 months postoperatively. Four of the seven patients (57%) enjoyed improvement in hearing class as defined by the guidelines of the American Academy of Otolaryngology-Head and Neck Surgery. CONCLUSIONS: Absent ABR waveforms have not been a negative prognostic sign regarding hearing preservation. CNAP monitoring is possible in these patients and likely helps to minimize iatrogenic cochlear nerve trauma. Patients with no ABR waveforms have hope of hearing preservation and even improvement following acoustic neuroma resection performed utilizing CNAP monitoring and hearing preservation surgical techniques.

Aged↗

The effect of nimodipine on cochlear potentials and Na+/K(+)-ATPase activity in normal and hydropic cochleas of the albino guinea pig.

In experimental endolymphatic hydrops (EEH) a decrease in the endocochlear potential (EP) has been reported and is thought to be due to decreased activity of the enzyme Na+/K(+)-ATPase in the stria vascularis. By stimulating Na+/K(+)-ATPase, the EP, and thereby cochlear function as a whole, might be restored. On the other hand, stimulation of stria vascularis Na+/K(+)-ATPase might result in excessive production of endolymph and thus produce or augment hydrops. In this study we have investigated the effect of intraperitoneally applied nimodipine on cochlear potentials and on Na+/K(+)-ATPase activity in the stria vascularis, both in normal cochleas (control) and in cochleas with EEH. Nimodipine is an L-type Ca(2+)-channel blocking agent with Na+/K(+)-ATPase stimulating properties at concentrations as low as 1.5 nM. The compound action potential (CAP), evoked by 2,4 and 8 kHz tone bursts was found to be depressed in the EEH ears with and without nimodipine treatment, and in the nimodipine treated control ears. Statistical analysis (ANOVA) showed that the effects of EEH and nimodipine on the CAP were additive. The negative summating potential (SP), measured extracochlearly at the apex, in response to 4 and 8 kHz tone bursts was significantly enhanced in the EEH ears. Nimodipine treatment did not affect the SP, neither in the control, nor in the EEH ears. Cytochemically, Na+/K(+)-ATPase activity appeared to be decreased in the oedematous stria vascularis of hydropic cochleas. No effect of nimodipine on Na+/K(+)-ATPase activity could be established ultracytochemically, neither in the controls nor in the EEH ears. In the lower turns of some of the nimodipine treated control cochleas a mild hydrops was seen during light-microscopic evaluation. Although it was not possible to prove a stimulatory effect of nimodipine on the enzyme Na+/K(+)-ATPase cytochemically, the finding of mild endolymphatic hydrops in nimodipine treated control ears suggests (a history of) increased endolymph production. This hydrops might be responsible for the depression of the CAP in the nimodipine treated ears.

Animals↗

Effects of arterial occlusion on endocochlear DC potential and cochlear blood flow in guinea pigs.

The present study was undertaken to investigate the role of collateral arteries in cochlear circulation by examining the effect of occlusion of branches of the basilar artery on endocochlear DC potential (EP) and cochlear blood flow (CBF). EP and CBF were measured at the basal turn of the cochlea during microclamp occlusion of the basilar artery, its branches and the posterior inferior cerebellar artery (PICA). CBF was measured with a laser Doppler flowmeter. Systemic blood pressure (SBP) increased at occlusion of the basilar artery, but was not influenced by any occlusion of its branches. Changes of EP and CBF at occlusion of the basilar artery were classified into two types: recovery type and non-recovery type. Thirty-five guinea pigs were classified into three groups according to the number of branches of the basilar artery: Group A with one branch in 10 animals (29%), Group B with two branches in 20 animals (57%), and group C with three branches in 5 animals (14%). From the results obtained at successive occlusions of branches of the basilar artery and PICA, it is clear that the anterior inferior cerebellar artery (AICA) supplies blood to the cochlea more or less in all animals, although the reduction of the blood volume by its occlusion is not enough to decrease EP in some animals. When vascular dysfunction occurs in AICA of such animals, other branches of the basilar artery and/or PICA will play an important role to maintain cochlear circulation.

Animals↗

Recovery of the endocochlear potential and the K+ concentrations in the cochlear fluids after acoustic trauma.

Intense noise stimulation (142 dB, 1/3-octave-band noise centred at 1 kHz for 1 h) causes damage mainly in the second turn of the cochlea. Several hours (3-5) after the noise exposure, the endocochlear potential (EP) was found to be very low (5.7 +/- 6.0 mV). Similarly, the K+ concentration in the endolymph (Ke+) had decreased to low values (18.9 +/- 9.5 mM). The return of EP and Ke+ to normal values took 5-20 days. In contrast to the Ke+ changes, the perilymph K+ concentration (Kp+) increased slightly after the noise exposure to 4.5 +/- 1.7 mM and returned to normal values one day after the exposure. Differences were found in the time course of the EP, Ke+ and Kp+ changes after the arrest of ventilat ion when animals with acoustic trauma were com,ared with normal healthy individuals. The anoxic EP in noise-exposed animals never decreased to values more negative than -20 mV. The results imply that the inner ear mechanisms maintaining positive EP, Ke+ and Kp+ are severely damaged after acoustic trauma and that their function is restored in 5-20 days. With respect to some parameters (decrease of the EP during anoxia, the value of anoxic negative EP, EP overshoot after reventilation) the inner ear mechanisms are, however, still abnormal.

Acoustic Stimulation↗

Dependence of endocochlear potential on vascular pH.

The vasculature of the inner ear was perfused with simple salt solutions which were buffered with HCO3/CO2, PO4 or Hepes (N-2-hydroxyethylpiperazine-N'-2-ethanesulfonic acid). Replacement of HCO3/CO2 with either PO4 or Hepes at constant pH led to a rapid decline of about 15 mV in the endocochlear potential (EP) to a new steady-state level which could be maintained for over 30 min. This effect was reversible. Changes in [HCO3] over a wide range (nominally 0-100 mM) at constant CO2 tension produced only small (less than 3 mV) changes in the EP. However, the EP declined markedly when [HCO3] was maintained constant at 25 mM while CO2 tension was lowered. The response to increased CO2 was more complex. Additional experiments were performed in which intracellular pH was presumably altered by vascular perfusion of NH4 (alkalinization), or propionate (acidification). Perfusion of ammonium led to a strong decline of the EP (-38.2 +/- 2.5 S.D.) while propionate produced a small positive shift of about 3-4 mV. Acetazolamide (1 mM) decreased the EP by 7.6 +/- 2.7 mV and 14.8 +/- 4.6 mV in HCO3/CO2 and Hepes medium, respectively, after 10 min perfusion; this effect was poorly reversible. These results suggest that intracellular pH has a strong influence on the level of EP and further demonstrate that vascular [HCO3] and pH are not critical parameters for generation of the EP.

Acetazolamide↗

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↗

Endocochlear potential and endolymphatic K+ changes induced by gap junction blockers.

OBJECTIVE: To examine the effects of gap junction blockers on the endocochlear potential (EP) and endolymphatic potassium concentration ([K(+)](e)). MATERIAL AND METHODS: The EP and [K(+)](e) were monitored using double-barreled ion-selective microelectrodes in the second turn of the guinea pig cochlea during perilymphatic perfusion. RESULTS: When the perilymphatic scalae of the cochlea were perfused with artificial perilymph containing 10 mM n-heptanol the EP was decreased by -8.8+/-1.4 mV (n=10), and this was accompanied by a decline in the [K(+)](e) of -6.7+/-2.1 mM (n=6). Perilymphatic application of 10 mM hexanol also produced declines in both the EP and [K(+)](e). In control studies, perilymphatic perfusion with 10 mM ethanol showed no remarkable changes in either the EP or [K(+)](e). Anoxia during perfusion with heptanol resulted in the generation of a negative EP, similar to the situation in controls. CONCLUSIONS: A decline in the EP together with a lowering of [K(+)](e) induced by long-chain n-alkanols, which act as gap junction blockers, may be explained by an interruption in potassium ion transport related to a gap junction dysfunction.

Alcohols↗