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Effects of acute styrene and simultaneous noise exposure on auditory function in the guinea pig.

Although styrene has been demonstrated to disrupt vestibular function acutely, parallel studies have not been conducted in the auditory system. This article presents data on the effects of acute styrene administration by injection and inhalation on cochlear function. No deleterious effect of the maximally tolerated styrene dose on hearing was identified when cochlear function was assessed using a within-subjects design. When guinea pigs were administered styrene by inhalation during a single 7-h period, normal auditory function was observed both 1 and 7 days later as compared to chamber controls which did not receive styrene. In some instances, the interactive effects of noise and simultaneous styrene inhalation were studied to determine whether chemical exposure might enhance the disruptive effects of noise on hearing. While a persistent noise-induced hearing loss was observed 1 day following exposure, subjects administered styrene simultaneously did not show a greater hearing loss than those receiving noise alone. Finally, when a 7-day recovery period for noise-induced hearing loss was interposed before audiometric testing, the combined exposure to styrene and noise was not more potent than noise alone in elevating auditory thresholds. Although auditory dysfunction has been reported following subchronic styrene administration, the current results do not support an ototoxic effect of styrene at the level of the cochlea with short-term exposure.

Action Potentials

Relation between discharges in auditory nerve fibers and the whole-nerve response shown by forward masking: an empirical model for the AP.

Whole-nerve action potentials evoked by a standard click were recorded from a gross electrode on the RW and the discharges of auditory nerve fibers to the same standard click were recorded from micropipette electrodes in the auditory nerve. The effect of a preceding tone burst (2, 4, or 8 kHz) upon the responses was measured for forward-masker intensities from 20 to 80 dB SPL. All forward maskers reduced the discharges of auditory nerve fibers to the standard click with the greatest reduction occurring for fibers with characteristic frequencies (CFs) near the masker frequency. The 4- and 8-kHz forward maskers produced similar effects on N1, P1, and N2 of the RW response. However, the 2-kHz forward masker produced enhancement at P1 and N2 in the RW response to the standard click. An empirical summation model of estimated elemental waveforms at latencies dependent on CF produces synthesized AP response waveforms which are similar to the observed RW response. The model permits the exclusion of discharges from segments along the cochlear partition in a manner similar to the effect of a forward masker. Alterations in the synthesized waveforms due to the exclusion of segments are similar in direction to the alterations observed in the RW responses for forward masking.

Acoustics

Influence of direct current on dc receptor potentials from cochlear inner hair cells in the guinea pig.

Inner hair cell responses to sound were monitored while direct current was applied across the membranous labyrinth in the first turn of the guinea pig cochlea. The current injection electrodes were positioned in the scala vestibuli and on the round window membrane. Positive and negative current (less than 100 microA) caused changes in the sound-evoked dc receptor potentials which were dependent on the sound frequency and intensity. The frequencies most affected by this extracellular current were those comprising the "tip" portion of the inner hair cell frequency tuning characteristic (FTC). The influence of current increased with increasing frequency. Positive current increased the amount of dc receptor potential for the affected frequencies while negative current decreased the potential. Current-induced changes (on a percentage basis) were greater for low intensity sounds and the negative current direction. These frequency specific changes are evidenced as a loss in sensitivity for the tip area of the FTC and a downward shift of the inner hair cell characteristic frequency. Larger current levels (greater than 160 microA) cause more complex changes including unrecoverable loss of cell performance. In separate experiments positive and negative currents (less than 1.1 microA) were injected into the inner hair cell from the recording electrode during simultaneous measurement of the sound-evoked dc receptor potential. This condition caused a shift in IHC sensitivity that was independent of sound frequency and intensity. Positive current decreased the sensitivity of the level of the cell while negative current increased the responses. The effect of current level on sound-evoked dc receptor potential was nonlinear, as comparatively greater increases in cell response were observed for negative than decreases for positive current. The intracellular current injection results are accounted for by the mechano-resistive model of hair cell transduction, where nonlinear responses with current level may reflect outward rectification. Response changes induced by extracellular current are evidence of current effects on both inner and outer hair cells. The frequency and intensity dependences are hypothesized to represent voltage mediated control of inner hair cell response by the outer hair cells.

Action Potentials

The effect of vasopressin upon the cochlear potentials in the guinea pig.

The change in the EP, CM, SP and AP during perilymphatic perfusion of vasopressin (antidiuretic hormone) was examined in the guinea pig. The EP was recorded with a microelectrode through the spiral ligament of the second turn. The CM, SP and AP were measured with the differential electrodes in the basal turn. The perfusion of vasopressin at concentration of more than 10(-5)M produced a reversible decrease in the EP. The extent of the EP decline was dependent upon the concentration of vasopressin. Abolition of the effect of vasopressin upon the EP by the resumption of respiration after transient asphyxia was observed. During the perfusion of vasopressin, the CM and AP decreased, while the negative component of the SP increased. The mechanism causing the effect of vasopressin upon the cochlear potentials is discussed.

Action Potentials

Effect of hypothermia on the cochlear potentials.

The effects of hypothermia upon the cochlear potentials were studied in 30 guinea pigs. Particular attention was paid to the transient increase in AP amplitude at a moderate temperature. CM and AP were recorded via an Ag-AgCl lead placed on the round window membrane. Although the CM amplitude and threshold, and the AP latency and threshold were both impaired concomitant with the lowering of body temperature, the AP amplitude exhibited a transient increase at the beginning of cooling (peak at 30 degrees C) and a decrease thereafter. Narrow-band analysis of AP revealed that this phenomenon was most prominent in the high-frequency region. When the cochlear efferent fibers (crossed and uncrossed olivocochlear bundle) were cut, this transient increase in AP amplitude disappeared. This phenomenon seems to be due to the difference in sensitivity to hypothermia between the efferent and afferent fiber systems.

Action Potentials

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

[Effects of furosemide on endocochlear potentials, auditory action potentials and summating potentials and the changes of inner ear pathology].

Guinea pigs were injected with furosemide 50 mg/kg (group A) and 25mg/kg (group B). Two minutes after injection, EP of group A decreased to -13.9mv while that of group B decreased to +65 mv. Also, AP of group A disappeared, and recovered at 8.5 mins. while AP amplitude of group B decreased to 78%. The SP value of group A changed from -14.5mv to +23.4mv 1 min after injection and returned to negative polarity in 12 min. Edema of stria vascularis was observed under light microscope. Transmission electron microscope showed edema between marginal cells and intermedia cells, cytoplasm of the marginal cell protruded to the cochlear duct, and cell membrane of outer hair cell folded. The finding of this study illustrates that furosemide inhibits the transportation of the active ions of cochlear duct tissue resulting in decrease of EP and alters the function of hair cells causing the change of AP amplitude. -SP depends on the ion transportation, the polarity can be inversed while large dosage of furosemide was used.

Action Potentials

Clinical usefulness of electrocochleography in Meniere's disease: an analysis of dehydrating agents.

Both electrocochleography and glycerol dehydration have an important diagnostic and prognostic role in the management of patients with endolymphatic hydrops, whether idiopathic as in Meniere's disease or secondary to certain diseases of the otic capsule. Abnormal electrocochleographic responses in a "normal" ear can be used to predict when Meniere's disease will become bilateral. There is a significant correlation between the effects of glycerol and of endolymphatic sac surgery on the pars inferior, at least over the span of several years. The subject hearing gains, the objective improvements in electrocochleographic responses, and the objective evidence of diminished inner ear impedance, all following proven glycerol dehydration, indicate that even in fairly advanced Meniere's disease, but especially in the earlier stages, reversibility is possible. This is a tantalizing therapeutic challenge.

Action Potentials

[The changes in the summating potential and morphology in the cochlea of guinea pigs with anoxia].

The dynamic changes in the CAP, SP and EP in the scale media were examined with single micropipet during anoxia and reventilation with oxygen. Also, the morphologic changes in the IHC, OHC and synapse were observed in this experiment. It was found that the amplitude of the SP and EP values declined with alteration in polarity of these value. The changes in polarity and amplitude of the SP followed the changes of CAP threshold induced by anoxia. The histologic examinations revealed no evidence of acetylcholinesterase (AChE) alteration in the synapse and no succinic dehydrogenase (SDH) changes in IHC appeared. However, the activity of SDH in the OHC decreased. The results suggest that the polarity and amplitude of SP were influenced passively by the changes of EP value. In addition, the changes of SP polarity from positive to negative during anoxia is due to the loss of modulation process of OHC to IHC, while the SP polarity from negative to positive during the supply of oxygen is caused by regain of the modulation process of OHC.

Acetylcholinesterase

A monaural space map in the guinea-pig superior colliculus.

Under anechoic conditions, a horizontal array of loudspeakers was used to investigate the representation of auditory space in the guinea-pig superior colliculus. We have previously demonstrated that in animals with both ears intact, there is a topographical representation of the azimuthal dimension of auditory space in the deep layers of this nucleus. In the present study, we have investigated the contribution of monaural and binaural cues to the generation of the auditory space map. Occlusion of one ear or unilateral cochlear destruction resulted in omnidirectional responses in all cells to white-noise stimuli more than 20 dB suprathreshold. The sensitivity of cells to the location of sound at or near threshold was, however, unchanged and we demonstrate the presence of a threshold, monaural auditory space map. This monaural space map was destroyed by removal of the contralateral pinna and concha which resulted in all cells responding best, at threshold, to sounds opposite the external auditory meatus. Measurements of cochlear microphonic (CM) potentials, although variable, revealed that the pinna and concha may result in location-specific changes in the spectral pattern at the tympanic membrane.

Animals

The effects of hyperbaric oxygen on experimental noise damage to the ears.

The effect of hyperbaric oxygen on cochlear microphonics, action potential of the auditory nerve, and brain stem response damaged by short exposure to noise is varied. Of 26 guinea pigs 14 showed a positive influence as measured by amplitudes. In 12 animals oxygen had little or no effect. The reason for this could lie in the individual reaction to the anesthetic of the section of the auditory nerve tested. The reaction of postmortem cochlear microphonics after hyperbaric oxygen treatment indicates oxygen diffusion through the round window.

Animals

Electrocochleography during intravenous infusion of cisplatin.

Extratympanic electrocochleography was performed on three patients following tobramycin injection and ten patients during cisplatin (cis-dichlorodiamine platinum II infusion. The compound eighth nerve action potential and the cochlear microphonic decreased considerably in magnitude up to 45 to 60 minutes after tobramycin injection, followed by a gradual recovery to normal in all three patients. During the eight hours of continuous cisplatin infusion, there was no significant change in the eighth nerve action potential and cochlear microphonic. The immediate effect of tobramycin on the cochlear output may be due to interference with the metabolism of the inner ear by the drug. The absence of electrocochleographic change during cisplatin infusion may be due to differences in the mechanism between cisplatin and aminoglycoside ototoxicity, or it may reflect the relatively nonototoxic potential of our chemotherapy regimen.

Adolescent

Clinical monitoring of the effects of gentamicin by electrocochleography.

Eight patients receiving prolonged treatment with gentamicin for bacterial endocarditis were monitored for possible ototoxicity using transtympanic electrocochleography as an adjunct to pure tone audiometry, vestibular function tests and serum gentamicin levels. An immediate effect of intravenous gentamicin on the cochlea, shown by changes in the whole nerve action potential and/or cochlear microphonic was recorded in seven patients, none of whom had experienced vestibular or auditory symptoms with gentamicin prior to testing. Two patients subsequently developed evidence of vestibular dysfunction, and a high frequency sensorineural hearing loss occurred in a third individual. There have been no previous report of the immediate effects of gentamicin on the human cochlea to date. The significance of these findings in routine clinical monitoring of ototoxicity is discussed in the light of clinical and animal evidence for the possible mode of action of aminoglycosides on the auditory and vestibular apparatus.

Action Potentials

Substance P increases cochlear blood flow without changing cochlear electrophysiology in rats.

Carotid artery infusions of substance P yielded reductions in systemic blood pressure and elevations in cochlear blood flow (CoBF), measured via laser Doppler flowmeter, with no alterations in cochlear action potentials or cochlear microphonics in Wistar-Kyoto rats. Additionally, direct micro-infusions of substance P into the anterior inferior cerebellar artery, which contributes to the local vascular perfusion of the cochlea, yielded elevations in CoBF with no changes in systemic blood pressure. Pretreatment with a specific substance P receptor antagonist, ([D-Pro2,D-Trp7,9]SP) via the carotid artery or the anterior inferior cerebellar artery, diminished subsequent substance P-induced vascular responses. These results suggest that endogenous substance P, like other vasoactive peptides, may interact with a substance P-specific receptor population in the cochlea and may therefore participate in the ongoing regulation of CoBF. These findings also support the premise that vasodilatory hormones, along with vasoconstrictive agents, may be involved in the autoregulation of CoBF.

Action Potentials

Measurements of perilymphatic oxygen tension in guinea pigs exposed to loud sound.

Using different types of custom-made oxygen-sensitive microelectrodes, the perilymphatic oxygen partial pressure (PO2) was determined in anesthetized guinea pigs. Cochlear temperature, heart rate, and arterial blood pressure and acid-base status were monitored. The PO2 in the basal scala tympani perilymph (200 microns below the round window membrane) was found to be 53 +/- 17 mmHg (mean +/- SD) in 33 normal animals. In 11 guinea pigs exposed to loud sound for 15 min (10 kHz pure tone, 125 dB SPL) there was on average a continuous decline in the perilymphatic PO2, which was significant only 30 min post-exposure. A considerable variation in response was found in individual animals. Mean arterial blood pressures showed a slightly increasing time course, while heart rates did not change significantly during the whole period of the experiment. Arterial acid-base status and PO2 values remained within normal limits and did not change significantly. Cochlear microphonics and compound action potentials were substantially decreased after acoustic overstimulation. The results are discussed with due consideration of sources of error.

Acoustic Stimulation

The protective effects of tirilated mesylate (U74006F) on ischemic and reperfusion-induced cochlear damage.

We have recently demonstrated that allopurinol, a blocker of free oxygen radical (FOR) production, and superoxide dismutase (SOD), a scavenger of FOR, protect the cochlea from damage associated with ischemia/reperfusion. The purpose of this present study was to determine if tirilated mesylate (U74006F), a potent inhibitor of lipid peroxidation, can also protect the cochlea from ischemia/reperfusion. Eleven Wistar-Kyoto rats were randomly assigned to two groups: (1) a control group (6 animals) that was exposed to 15 minutes of cochlear ischemia by clamping the anterior-inferior cerebellar artery (AICA), followed by 15 minutes of reperfusion, and (2) a drug-treated group (5 animals) that received U74006F before ischemia/reperfusion. In the control group, the tone burst-evoked compound action potential (CAP) recorded from the round window (RW) was abolished and cochlear microphonic (CM) was reduced. In contrast, the U74006F-treated animals showed post-reperfusion sensitivity in CAP, and less of a CM threshold shift. We interpret these results to indicate that U74006F lessens cochlear damage occurring as a result of ischemia/reperfusion and supports the hypothesis that FOR-induced lipid peroxidation may be partly responsible for the cochlear damage that occurs from ischemia.

Action Potentials