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PubMed2001

Summating potential in the guinea pig cochlea after perilymphatic perfusion with arginine-vasopressin.

We hypothesized that arginine-vasopressin (AVP), the natural vasopressin in the guinea pig, might increase the cochlear summating potential, indicating an increase in endolymphatic volume. Guinea pig cochleas were perfused with artificial perilymph for 15 min, with or without AVP (2 x 10(-6) M). In 1 group of animals, summating potentials (SP), compound action potentials and cochlear microphonics evoked by 2, 4 and 8 kHz tone bursts were measured with an apically placed electrode 15 min, 1 and 2 h after perilymphatic perfusion. In another group of animals the SP and endocochlear potential (EP) were measured simultaneously in the scala media during and after perfusion. In both groups the SP had increased significantly 15 min after perfusion with AVP and this increase was reversible. At the concentration of AVP used the increase in SP was not related to EP alterations. On light microscopic examination of the cochlea no evident increase in scala media volume could be detected. The increase in the SP (a sensitive indicator of acute endolymphatic hydrops) after perfusion with AVP suggests that this neuropeptide plays a role in the regulation of the ion and fluid balance in the cochlea.

Action Potentials↗
PubMed1996

Effects of superoxide dismutase and U74389G on acute trimethyltin-induced cochlear dysfunction.

Reactive oxygen species (ROS) generation has been implicated in the ototoxicity induced by several pharmaceutical agents. The present study examined the efficacy of the ROS scavenger polyethylene glycol-conjugated superoxide dismutase (PEG.SOD), and a 21-aminosteroid (U74389G), in ameliorating the acute cochlear dysfunction induced by the environmental ototoxicant trimethyltin chloride (TMT). Thirty pigmented guinea pigs were divided into six experimental conditions, as defined by preexposure and exposure administrations: saline-saline, PEG.SOD-saline, U74389G-saline, saline-TMT, and U74389G-TMT. Electrophysiological potentials (compound action potential (CAP) and cochlear microphonic (CM) were recorded for 10 acoustic frequencies, and then a preexposure agent (U74389G, 4.5mg/kg; PEG.SOD, 10,000 U/kg; or 0.9% saline) was administered i.v. Thirty minutes later, potentials were retested, and an exposure agent (0.9% saline or TMT, 0.5 mg/kg) was administered i.p. CM and CAP were retested at 30, 60, and 90 min postexposure time points, in order to assess changes in auditory responsiveness. Mean changes in 1.0-microV root mean square CM isopotential values did not differ significantly in any group from those of saline-saline controls. In the saline-TMT group, CAP thresholds increased significantly at all test frequencies relative to those of the saline-saline control group. While mean CAP threshold shifts in the U74389G-TMT group were as great as those in the saline-TMT group, such values in the PEG.SOD-TMT group were significantly lower. These results suggest that ROS formation may be involved in acute TMT-induced CAP disruption, for which PEG.SOD, but not U74389G, provides partial protection.

Action Potentials↗
PubMed1990

The ototoxic mechanism of cisplatin.

The ototoxic mechanism of cisplatin was investigated. Potentiation of cisplatin ototoxicity by furosemide and amino-oxyacetic acid (AOAA) was observed. Substantial hearing loss in cisplatin-deafened animals was accompanied by normal values of the endocochlear potential and a reduction in the sensitivity of the 2f1-f2 distortion products. The loss in dB of the sensitivity of the distortion products correlated extremely well with the loss of the neural sensitivity in dB. There was also a relationship between the fractional reduction of the low frequency (1000 Hz) microphonic potential and hearing loss in dB. Iontophoresis of cisplatin into scala media resulting in the immediate loss of neural thresholds at the site of iontophoresis. It is concluded that cisplatin caused the hearing loss by blocking OHC transduction channels.

Aminooxyacetic Acid↗
PubMed1991

Analog model of human click-elicited SP and effects of high-pass filtering.

Recent advances in electrode design have helped to rekindle clinical interests in noninvasive electrocochleography--to enhance auditory brain stem response (ABR) recordings (namely, wave I) and to screen Meniere's disease. The salient feature of the response in suspected cases of endolymphatic hydrops is an unusually large summating potential (SP). Since the SP is a DC potential, conventional wisdom suggests the use of relatively low cutoff frequencies (i.e., long-time constants) for recording, but this may degrade the recording due to the presence of excessive low-frequency noise. However, the click-elicited SP also is a transient of relatively short duration, considering the characteristics of the click. This may permit more liberal high-pass filtering with acceptable wave-form distortion. This is a report of findings obtained using an analog model for SP generation and recordings from normal subjects using an electrode placed directly on the tympanic membrane. Responses were obtained using various low-frequency cutoffs. Cutoffs up to 30 Hz caused little distortion. Even in the face of considerable distortion at the highest cutoffs (100 and 300 Hz), the SP remained detectable and the SP:AP essentially unchanged. Therefore, higher filter settings may be used in recording the SP than commonly assumed, although the decreased amplitudes of the component potentials may not be tolerable under all clinical test conditions.

Adult↗
PubMed1987

An advanced cochlear echo technique suitable for infant screening.

An advanced cochlear echo test technique has been specially developed to tackle some specific problems associated with measurements from infants. The test procedure and data processing combination has greatly improved noise immunity and has given very reliable results on poorly co-operating children. Technical details are given and the results of a study of 105 ears from 55 children are presented. The potential of the advanced technique as a screening test is discussed.

Adolescent↗
PubMed1992

[Changes in transitory evoked otoacoustic emissions in chemotherapy with cisplatin and 5FU].

The aim of this study was to detect changes of transient evoked otoacoustic emissions (TEOAE) during chemotherapy with cisplatin and fluorouracil (5FU). A review of the literature reveals that the incidence of cisplatin ototoxicity varies from 9% to 50%; this variation is due to differences in doses, duration of administration, to the criteria for ototoxicity and on audiological methods. Three cycles of chemotherapy (1000 mg/m2 5FU from day 1 to 5 and 100 mg/m2 cisplatin on day 1) were given to 12 patients; the OAE were measured before chemotherapy and after each administration. In 86% of the ears measured we found changes in the TEOAE; the mean values for the amplitude of the TEOAE decreased about 13% after the end of the chemotherapy. Pure tone thresholds were reduced in almost 50% of the measured ears. The decrease of amplitude of TEOAE is an early sign of an ototoxic secondary effect, probably due to damage to the outer hair cells. TEOAE is a sensitive method for detecting ototoxicity in cisplatin-treated patients and more reliable than pure-tone audiometry or evoked acoustic potentials.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1991

Auditory evoked potentials in the Japanese monkey.

Auditory sensitivity based on auditory brain stem response (ABR), whole nerve action potential (AP), and cochlear microphonics (CM) to tone bursts of 0.5-8 kHz were compared with behavioral audiometry in the Japanese monkeys. Although sensitivity loss at 4-6 kHz was observed in these potentials, an increase in sensitivity at 8 kHz was obtained only in the ABR. Thus the sensitivity loss at 4-6 kHz originates at the peripheral system and the increased sensitivity at 8 kHz originates at the central.

Action Potentials↗
PubMed1997

Identification of the nonlinearity governing even-order distortion products in cochlear potentials.

In order to characterize the cochlear transducer nonlinearities which are involved in the generation of the summating potential (SP), we investigated the effect of a change in the electrical operating point of the cochlear transducer on the SP. The electrical operating point of the cochlear transducer was affected by suppressing reversibly the endocochlear potential (EP). This was realized by intravenous injection of furosemide in guinea pig. A differential recording technique was used in the basal turn of the cochlea to measure locally generated even-order distortion products: the SP and the second harmonic component (2F0) of the cochlear microphonics (CM). These potentials were evoked by 2 and 8 kHz stimuli presented at 60 dB SPL. Following furosemide injection, the SP changed polarity twice over time. The zero crossings of the SP coincided with a minimum in the amplitude of 2F0. Concomitantly, the phase of 2F0 shifted about 120 degrees. The changes in the electrical even-order products were comparable to the changes that occurred in a mechanical even-order intermodulation distortion product (the difference tone F2-F1 otoacoustic emission) after furosemide application (Mills et al., J. Acoust. Soc. Am. 94 (1993) 2108-2122). The combined results suggest that only one sigmoidal transfer function may account for the SP, 2F0, and the emission of the difference tone F2-F1, and that shifts in the operating point of the transfer function would be the major cause behind the furosemide-induced changes in the even-order distortion products. The sigmoidal transfer function is likely associated with the mechano-electrical transducer channel at the apical pole of the outer hair cell.

Acoustic Stimulation↗
PubMed1991

Evaluation of electrocochleographic audiogram determination in infants.

An evaluation was made of results of electrocochleography (ECoG) in a group of 75 children, tested during the last four years in the ENT department of the Leiden University Hospital. Eleven years was taken as the upper age limit; 79% of our group were younger than three and a half years. In only 60% of the children the cause of the hearing loss was clarified. In this group maternal rubella followed by meningitis and retardation were the most frequent cases of deafness. Cochlear microphonics (CM) could be measured in all the children. Examples are given of cochlear responses of children belonging to 6 different threshold categories. The responses of the largest category (56 children) with the highest loss (larger than 80 dB) were very abnormal. For the categories with less hearing loss the ECoG was not restricted to threshold determination and the origin of the hearing loss could be demonstrated, while a contribution of conduction loss could be derived from a horizontal shift of the latency-intensity function to higher intensity levels. The potentialities and limitations of ECoG and brainstem electric response audiometry (BERA) for threshold determination are discussed, particularly against the background of the time consumption of both procedures and the invasive character of ECoG.

Audiometry, Evoked Response↗
PubMed1995

Effect of cisplatin administration on the electrochemical composition of endolymph in the rat cochlea.

The effect of cisplatin on the electrochemical composition of the cochlear endolymph was studied in Long-Evans rats three days after a single intraperitoneal injection (8 mg/kg b.w.). A dose 2/3 of LD50 induced a decrease of the endolymphatic concentration of potassium whereas the endocochlear potential was unaffected. The discrepancy between these two findings indicated that cisplatin did not alter the mechanisms involved in the genesis of the endocochlear potential but modified the passive K transport into endolymph.

Analysis of Variance↗
PubMedDate not supplied

Cochlear potentials and oxygen associated with hypoxia.

In the guinea pig, during general hypoxia produced by shutoff of respiratory air, oxygen-sensitive microelectrodes detect a decrease in oxygen concentration in the fluids of the tunnel of Corti before detecting a decrease in scala media oxygen concentration. The present experiments were designed to measure the cochlear microphonic (CM) potential generated by the organ of Corti when vibrated by a microprobe on the basilar membrane along with the oxygen decline in both tunnel and scala media to see upon which source of oxygen CM is dependent. Because oxygen concentration in both areas can decrease considerably before CM is affected, the recovery following a brief period of hypoxia is a more accurate measure. Because CM starts a recovery before scala media oxygen, the positive endolymphatic potential (EP) was also measured to determine its role in the generation of CM. Our interpretation of the course of events is that CM is partially dependent upon oxygen supplied to the extracellular spaces of the organ of Corti by the spiral vessels and upon EP that, itself, is dependent upon several factors. The data indicate that EP plays a more complex role than that of providing a current flow for modulation by a resistance varying with vibration.

Animals↗
PubMed1985

Morphology, synaptology and electrophysiology of the developing cochlea.

The development of synapses clearly differentiates the two kinds of cochlear receptors inner (IHC) and outer (OHC) hair cells. An adult-like pattern of innervation can be seen very early below the IHCs: both afferent and efferent (mainly axo-dendritic) synapses are formed before the onset of function. At the OHC level, drastic changes occur: numerous afferent dendrites retract as the large efferent endings arrive and synapse with the hair cell. This synaptic OHC remodelling coincides with maturation of compound action potential (AP) parameters, such as the "S" -shape of the input-output curves and the sharpening of AP tuning curves.

Animals↗
PubMed1984

Dynamic aspects of guinea pig inner hair cell receptor potentials with transient asphyxia.

DC and AC receptor potentials of cochlear inner hair cells in response to tone bursts of various frequencies and intensities were continuously measured during and following periods of transient asphyxia. The effects of asphyxia were most pronounced for low sound pressure level (SPL) acoustic stimuli near the characteristic frequency (CF) of the inner hair cell, leading to vulnerability of the 'tip' of the cell's frequency tuning curve (FTC). The resulting changes in the shape of the FTC are, first, a reduction in tip criterion sensitivity of 10-20 dB without significant loss in sharpness of tuning. Later, when the full effect of 30-45 s asphyxia occurs, tip sensitivity loss between 30 and 65 dB is accompanied by greatly broadened tuning and a shift downward in frequency of the CF by greater than 1/4 octave. The CF shift is due to a progressive loss of high frequency sensitivity. The linear segment of the input-output (intensity) function, plotted as log DC receptor potential versus SPL (at the original CF), becomes longer during the early phase asphyxia, and the slope of the segment declines by 50%. At high SPLs, for all frequencies, the time course of the receptor potential change was similar in shape to that exhibited by the endocochlear potential (EP). In particular, for high sound levels, the recovery of response matches the EP while for low level tip frequency sounds recovery is protracted. No difference between the decline of the AC and DC receptor potentials at CF was observed. Inner hair cell resting membrane potential (Em) hyperpolarized during asphyxia by 2-6 mV, correlating with the change in EP according to a ratio of 1/10 (Em/EP).

Animals↗
PubMed1996

Suppression in auditory-nerve fibers of cats using low-side suppressors. II. Effect of spontaneous rates.

The responses of auditory nerve fibers with different spontaneous rates were studied in anesthetized cats, using harmonically related characteristic frequency (CF) tone and suppressor (SUP) tone (50-2000 Hz) as stimuli. The relative-response index, defined as the ratio of the maximum response level in the two-tone segment to the response level in the CF-alone segment, at or near the intensity of maximum suppression (i.e., where the two-tone rate was lowest), was dependent on fiber's spontaneous rate (SR). For all the SUP frequencies used, lower-SR fibers almost always showed values less than unity, while high-SR fibers almost always gave values near or greater than unity. The phase of maximum suppression was not dependent upon fiber SR. In one experiment, a pair of low- and high-SR fibers with the same CF (12 kHz) were recorded consecutively in the same electrode penetration, and were studied with the same stimulus parameters. Their temporal responses showed dramatic temporal resemblances, with very similar phases of suppression and response. But the relative-response indexes were different. The similarities in the lower- and high-SR fibers support the idea that the basic response and suppression patterns in all fibers are formed at or before the inner hair cell (IHC) stage, while the differences suggest that processes more central than the IHC receptor potential are important in determining the magnitudes of suppression, particularly in the lower-SR fibers.

Acoustic Stimulation↗
PubMed1983

Generation mechanism of the negative endocochlear potential during early stage of anoxia.

To investigate the generation mechanism of the -EP in anoxic cochlea, the perilymphatic space was perfused with solution of various K+ concentrations in 38 guinea pigs when the -EP was maximally reduced by anoxia. Although the perfusion of scala tympani and vestibuli with Ringer-Locke solution or that of scala vestibuli with 154 mM K+ solution did not have any effect upon the -EP, the potential was elevated to 0 mV when the scala tympani was perfused with 154 mM K+ solution. Furthermore, the elevation of the potential was less remarkable when the K+ concentration in perfusate was reduced. The level of the potential during perfusion was closely related to K+ concentration in perfusates. The present results strongly suggest that the -EP is the result of the K+ diffusion potential and this diffusion mechanism is performed through the organ of Corti.

Animals↗
PubMed2004

The influence of transducer operating point on distortion generation in the cochlea.

Distortion generated by the cochlea can provide a valuable indicator of its functional state. In the present study, the dependence of distortion on the operating point of the cochlear transducer and its relevance to endolymph volume disturbances has been investigated. Calculations have suggested that as the operating point moves away from zero, second harmonic distortion would increase. Cochlear microphonic waveforms were analyzed to derive the cochlear transducer operating point and to quantify harmonic distortions. Changes in operating point and distortion were measured during endolymph manipulations that included 200-Hz tone exposures at 115-dB SPL, injections of artificial endolymph into scala media at 80, 200, or 400 nl/min, and treatment with furosemide given intravenously or locally into the cochlea. Results were compared with other functional changes that included action potential thresholds at 2.8 or 8 kHz, summating potential, endocochlear potential, and the 2 f1-f2 and f2-f1 acoustic emissions. The results demonstrated that volume disturbances caused changes in the operating point that resulted in predictable changes in distortion. Understanding the factors influencing operating point is important in the interpretation of distortion measurements and may lead to tests that can detect abnormal endolymph volume states.

Animals↗
PubMed1984

[Sound pressure isopotential levels for the microphonic potential of the internal ear].

The amplitude of gross microphonic potential of guinea pigs was used for output regulation of the generator of sinusoidal and narrow-band noise signals at continuous changing of frequencies. Thus isopotential contours of sound pressure levels (SPL) were obtained. The dynamics of the isopotential SPL on different levels within the range of 50-20 000 Hz, is described.

Acoustic Stimulation↗