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Cochlear potentials of guinea pigs with experimentally induced renal failure.

In order to investigate the relationship between renal failure and hearing loss, the authors made a guinea pig model with experimentally induced renal failure and examined cochlear potentials (N1, CM and EP). When renal damage was greater, the amplitudes of N1 and CM were decreased and the latency of N1 was prolonged, but EP was within normal range. The sensory cells of the cochlea were considered responsible for the hearing loss in the guinea pig model. No pathological alterations of the cochlea were revealed by a light microscopy. It is suggested that the etiology of the hearing loss was due mainly to metabolic disturbances such as uremic toxins, electrolyte imbalance or endocrine abnormalities.

Acute Kidney Injury↗

Transient changes in cochlear potentials and DPOAEs after low-frequency tones: the 'two-minute bounce' revisited.

After exposure to a loud, non-traumatic low-frequency tone, auditory thresholds are elevated. Thresholds recover to normal in a non-monotonic manner, decreasing rapidly at first before increasing again, until they finally decrease monotonically towards normal. Although the transient elevation of thresholds after the initial improvement was originally called a 'bounce' by Hirsh and Ward (1952), Kemp (1986) suggests that the initial rapid recovery is the oddity: under some conditions a low-frequency tone can produce hypersensitivity in otoacoustic emissions, psychophysical thresholds, and perceived loudness (Kemp's 'bounce') without a later elevation of threshold (Hirsh and Ward's 'bounce'). Kemp also suggested that the transient hypersensitivity was caused by changes in the sensitivity of the active process within the cochlea. We have investigated the origin of this transient hypersensitivity (Kemp's bounce) in guinea pigs, recording cochlear potentials (CM, CAP, SP and EP) and otoacoustic emissions (DPOAEs at f2-f1, 2f1-f2, 2f2-2f1 and 3f1-2f2). Our results indicate that the bounce does not require neural activity, but is probably produced by non-neural cochlear mechanisms, possibly a transient decrease in the permeability of the organ of Corti which produces a small but significant change in standing current through outer hair cells. At least part of these changes, which are reduced as the stimulation frequency increases, and absent above 2 kHz, seem due to a small and transient movement of the cochlear partition towards scala tympani, probably due to a transient osmotic imbalance.

Acoustic Stimulation↗

Mechanisms of endocochlear potential generation by stria vascularis.

It is commonly accepted that the endocochlear potential (EP) of the cochlea is generated by an electrogenic transport of potassium into scala media by the marginal cells of stria vascularis. We have studied the potential and potassium concentration gradients as stria vascularis was penetrated with double-barreled potassium selective electrodes in the guinea pig cochlea. Our data demonstrate that a region exists in stria which is positively polarized (higher than the EP), but which has a low (perilymph-like) potassium composition. It is concluded that EP cannot be generated by the marginal cells alone but may involve passive potassium movement across the apical membranes of the basal cells. A model is presented which is consistent with many anatomical and physiological features of stria vascularis.

Animals↗

The effects of short noise exposures in the guinea pig.

Guinea pigs have been exposed to 20 kHz at 120 dB SPL for exposure durations of 7.5, 6.5, 5.0, and 3.25-min and killed either 3 or 12 weeks post-exposure. One series of guinea pigs exposed for 30-min had cochlear potentials recorded 3 weeks post-exposure. The damage was assessed by surface preparations and quantified as percentage hair cell loss per segment in every row, total number of outer, and inner hair cells missing and the area of total outer hair cell damage. A significantly smaller number of ears were found to be damaged after the shortest exposures, but no significant differences could be detected in the amounts of damage when all the series were compared. Myelinated nerve fibre degeneration had increased after the longer post-exposure interval, but no such differences were observed in the sensory hair cell degeneration.

Animals↗

Intravascularly applied K(+)-channel blockers suppress differently the positive endocochlear potential maintained by vascular perfusion.

We studied the effects of several K+ channel blockers on the positive endocochlear potential (EP) of guinea pigs undergoing perfusion via the anterior inferior cerebellar artery. The EP level was reversibly suppressed by 50-60% in the presence of Ba2+ (2 mM), quinine (2 mM) or verapamil (1 mM) in the perfusate, but not significantly affected by tetraethylammonium (20 mM) or 4-aminopyridine (5 mM). Although the effective site(s) of these blockers at the cell level has not been located yet, these findings indicate an important role for a K+ conductance in the generation of the EP.

Analgesics, Non-Narcotic↗

The nature of the ototoxic actions of ethacrynic acid upon the mammalian endolymph system. I. Functional aspects.

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

Animals↗

Pathophysiological mechanisms of hearing loss.

An understanding of auditory transduction in the ear can contribute to a better comprehension of the pathophysiological mechanisms which give rise to hearing loss. The incoming sound sets up a mechanical traveling wave which begins at the base and progresses along the basilar membrane, reaching a point of maximal displacement. The region of maximal displacement is a function of stimulus frequency. The mechanical displacement, by directly opening ion channels in the stereocilia of the hair cells, induces changes in the electrical potential of the hair cells. This initial stage is called mechano-electrical transduction, and in the normal ear, is followed by a stage of electro-mechanical transduction based on the ability of the outer hair cells to respond to the electrical changes induced in them with a change in their length. This "electromotility" presumably provides mechanical feedback to the basilar membrane, augmenting its mechanical displacement. This is called the cochlear amplifier, providing the ear with improved sensitivity and frequency discrimination. Most forms of sensori-neural hearing losses (affecting the inner ear) are due to a lesion to some part of this cochlear amplifier (e.g. noise induced hearing loss, ototoxic drugs) and are therefore characterized by auditory threshold elevations and poorer frequency discrimination.

Acoustic Stimulation↗

Furosemide ototoxicity: clinical and experimental aspects.

Furosemide is an ototoxic diuretic. Furosemide injection is followed by a rapid, but reversible decrease of the endocochlear potential and eighth nerve action potential with a more gradual decrease of the endolymph potassium concentration. In contrast to the reversible effects of furosemide alone on the cochlea, the combination of kanamycin with furosemide resulted in irreversible changes in cochlear function which were associated with elevated levels of kanamycin in the blood and perilymph of the experimental animals. There was a striking similarity between the blood level measured by high pressure liquid chromatography at the time of recovery of auditory function in experimental animals and the ototoxic blood levels proposed by others in clinical literature. These findings help to provide a pharmacologic basis for the clinical observation of furosemide-induced hearing loss.

Animals↗

[Cochlear potentials and reduced blood supply].

In cats the mean arterial blood pressure (MABP) was reduced to 40 or 30 mm Hg by controlled hemorrhage. In 3 animals the cochlea action potentials (CAP) are not changed between 30 and 380 Min by 40 mm Hg MABP. In 4 animals we saw a latent or permanent decrease of CAP between 4 and 115 Min by 30 mm Hg MABP. A singular experiment shows, that a CAP-decrease is caused by injection of an acetylcholin blockade substance. We did not find a correlation to the length of time of the ischemia and a CAP decrease. We found an exact correlation to the hypovolemic sympathetic palsy and a CAP decrease. In reduced blood perfusion the cochlea of cats is more resistant than the brain.

Animals↗

[Electrophysiological study of inner ear barotrauma in guinea pigs; comparison with scanning electron microscopic findings].

To investigate the mechanism of barotrauma to the inner ear, we used electrophysiologic methods to evaluate guinea pigs exposed to such trauma, and compared the findings with those observed by scanning electron microscopy (SEM). Guinea pigs with good Preyer's reflexes were studied. In those animals that showed a loss of or decrease in Preyer's reflexes and/or nystagmus following exposure to an increase and decrease in pressures in a high-pressure chamber, we measured compound action potentials (CAPs) and cochlear microphonics (CMs) 7-11 days after the exposure. The pressure was increased from 1 ATA to 2 ATA over 30 sec and maintained for 10 min, then pressure was decreased to 1 ATA over 30 sec. Specimens obtained from animals in which CAPs and CMs could be measured were prepared for SEM examination. CAPs and CMs were measured at decreasing 5 dB increments to the visual threshold level of detection with tone bursts at 1, 2, 4 and 8 kHz. Based on the CAPs measured 7-11 days after exposure, guinea pigs were divided into two groups by CAP thresholds, those with severe damage and those with mild damage. None of the animals showed moderate damage. The group with high CAP thresholds showed severe damage to hair cells on SEM, while the group with low CAP thresholds showed no specific morphological abnormalities on SEM. It appeared that some guinea pigs with normal SEM findings following barotrauma to the inner ear did not achieve complete recovery of hearing. From these results, it was speculated that some animals had sustained reversible damage in the mild group and that these animals had recovered from moderate damage. The elevation of CMs was usually not high compared to that of CAPs in the high frequency area, and 4 animals showed CAP and CM separation above 30 dB at 8 kHz. These findings suggested that the group with severe damage exhibited multiple patterns of injury.

Action Potentials↗

Effects of betahistine on vestibular receptors of the frog.

Betahistine is widely used in the symptomatic treatment of peripheral and central vestibular disorders. However, its remains unknown whether the drug can act directly on inner ear sensory organs. To this end, the effects of betahistine (10(-7)-10(-2) M) were examined on isolated preparations of frog semicircular canal mounted in a double-celled bath which allowed drug administration both in the endolymphatic and in the perilymphatic fluid. The effects of betahistine were evaluated by recording ampullar receptor potentials and nerve firing rate both at rest and during mechanical stimulation of the isolated preparation. The results demonstrated that endolymphatic administration of betahistine had no effect, whereas its perilymphatic administration could reduce greatly ampullar receptor resting discharge but had little effect on mechanically evoked responses. This observation may explain the anti-vertigo effects of betahistine. Vertigo is normally due to uncontrolled changes in vestibular receptor resting discharge. It is therefore probable that any factor able to reduce the resting firing rate of vestibular receptors and, in consequence, its variations, may have an anti-vertigo action.

Animals↗

Influence of middle ear immune response on the immunological state and function of the inner ear.

According to clinical experience, a causative correlation between otitis media and sensorineural hearing loss is likely. During an otitis media, inflammatory mediators should be released and diffuse through the round window membrane to cause an immune response of the inner ear. Using 20 guinea pigs, an immunologically caused otitis media was induced. Auditory evoked potentials were registered by means of electrocochleography and electric response audiometry from day 0 to day 7. Each time, before and after starting the immune response serum, middle ear effusion and perilymph were sampled and the concentration of interleukin-2 (IL-2) analyzed. Decalcified temporal bones were examined immunohistochemically. In this study, IL-2 was found in the middle ear effusion and perilymph, and there was evidence of an immune response of the inner ear during an otitis media. Histological results were in close correlation with this event. Electrophysiological data showed conduction deafness and signs of sensorineural hearing loss with a maximum at day 3.

Animals↗

Change in K+ activity of the scala media produced by vasopressin.

The endocochlear potential (EP) and K+ activity in the scala media were recorded by means of K+-sensitive double-barreled microelectrodes in the second turn of the cochlea of the guinea pig during the perilymphatic perfusion with vasopressin. Vasopressin produced a decrease in K+ activity in the scala media following a decrease in EP. The decrease in K+ activity in the scala media relative to the EP reduction produced by vasopressin was not significantly different from that by perilymphatic perfusion with furosemide. The present results suggest that vasopressin changes the EP by acting on the stria vascularis.

Animals↗

Underestimation of auditory fatigue as measured by the compound action potential.

The action potential (AP), summating potential (SP), and cochlear microphonic (CM) were measured in rats in response either to clicks or pure tones prior to and following 3 min of exposure to pure tones at a level 5 db less than that which produced maximum CM. The ratio, in decibels, between pre-exposure and post-exposure potentials, for the same exposure and probe stimulus parameters, was taken as an index of decrement. The relative reduction in voltage resulting from the exposure was greater for the SP than for the AP when these potentials were elicited with 20-msec probe tone bursts between 70-80 db SPL having instantaneous rise times. However, for weaker probe levels within 20 db of that yielding AP potentials of 1 mu V, the AP and SP bpth exhibited similar losses. The CM and the click-evoked AP showed essentially no decrement. These results suggest that the SP might be a better indicator of noise-induced auditory decrement (fatigue?) than the CM. Theories of central auditory fatigue may be based on incorrect interpretations of previously published data obtained from cochlear and neural recordings.

Action Potentials↗

The influence of ototoxic drugs on brainstem auditory evoked potentials in man.

To examine the short- and long-term consequences of ototoxic drug administration, the brainstem auditory evoked potentials (BAEP) have been recorded in patients undergoing treatment with aminoglycosides antibiotics. It appears that the rapidity of the i.v. injection influences the short-term consequences of the drug administration. The long-term consequences may be reversible. Their reversibility could depend on the status of the ear before the first injection of ototoxic drug. In conclusion, BAEP may be useful as a means of atraumatic monitoring of the auditory function of patients treated with aminoglycosides antibiotics, the non-invasive character of this technique allowing it to be repeatedly used in both adult and young patients.

Acoustic Stimulation↗

Summating potential/action potential ratio in perilymph fistula.

A prospective study of electrocochleography in patients with clinically suspected perilymph fistula was undertaken to determine its predictive value in that disorder. One hundred forty-four patients suspected of having perilymph fistula had electrocochleography performed--34 of these (39 ears) had exploratory tympanotomy. Of the 19 ears with normal preoperative summating potential/action potential (SP/AP) ratio, ten had perilymph fistula identified at the time of surgery. Of the 20 ears with abnormal SP/AP ratio, 16 had perilymph fistula confirmed at exploration, 18 had resolution of symptoms after oval window and round membrane grafting, and only one ear had postoperative persistence of the abnormal SP/AP ratio. This study suggests that an abnormal SP/AP ratio is not only predictive of endolymphatic hydrops, but also of perilymph fistula (both problems of inner ear fluid imbalance). This study also suggests that, while abnormal SP/AP ratio is fairly specific for inner ear fluid imbalance, it is not sensitive.

Adolescent↗

Age-related decreases in endocochlear potential are associated with vascular abnormalities in the stria vascularis.

The density and diameter of strial capillaries were assessed in whole-mount preparations of the cochlear lateral wall from 18 gerbils aged in quiet for at least 36 months. Following morphometric analysis, histopathologic changes in selected regions of the lateral wall were examined by light and transmission electron microscopy. Alterations in strial vasculature were compared with the endocochlear potential (EP) measurements from the same ear. Vascular degeneration occurred in a segmental fashion in that regions of atrophic capillaries were found throughout the cochlea but primarily in the apical and lower basal turns and in the hook. The amount of stria with normal capillaries varied greatly among the aged ears, ranging from 19 to 87%. The resting EP also varied markedly, ranging from 23 to 83 mV. Little correlation was found between vascular alterations and the corresponding EP value from individual cochlear turns. However, significant correlations were found between the total strial area with normal vasculature and both the mean EP value and that recorded at either the round window or first turn in that ear.

Aging↗

Age-related decreases in endocochlear potential are associated with vascular abnormalities in the stria vascularis.

The density and diameter of strial capillaries were assessed in whole-mount preparations of the cochlear lateral wall from 18 gerbils aged in quiet for at least 36 months. Following morphometric analysis, histopathologic changes in selected regions of the lateral wall were examined by light and transmission electron microscopy. Alterations in strial vasculature were compared with the endocochlear potential (EP) measurements from the same ear. Vascular degeneration occurred in a segmental fashion in that regions of atrophic capillaries were found throughout the cochlea but primarily in the apical and lower basal turns and in the hook. The amount of stria with normal capillaries varied greatly among the aged ears, ranging from 19 to 87%. The resting EP also varied markedly, ranging from 23 to 83 mV. Little correlation was found between vascular alterations and the corresponding EP value from individual cochlear turns. However, significant correlations were found between the total strial area with normal vasculature and both the mean EP value and that recorded at either the round window or first turn in that ear.

Acoustic Stimulation↗