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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↗

[The electro-physiological change of guinea pig cochlea caused by intracochlear perfusion of sodium salicylate].

OBJECTIVE: To investigate the way how sodium salicylate affects cochlear function and discuss its possible mechanism. METHOD: Sodium salicylate was perfused through guinea pig cochlea. The thresholds and input-output (I/O) functions of compound action potential (CAP) and summating potential (SP) were monitored during the perfusion. RESULT: Sodium salicylate caused a significant change of CAP and SP threshold as well as I/O curve. The relationship between CAP and SP threshold change at 10 kHz during perfusion with 10 mmol/L salicylate tends to be 1:1. CONCLUSION: Outer hair cells are most likely to be the sites of action of sodium salicylate and this action on the outer hair cell active process might lead to its ototoxicity.

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↗

An electrophysiologic study of the guinea pig inner ear following low pressure barotrauma.

We examined electrophysiologic and morphologic changes following low pressure barotrauma in 25 guinea pigs. Compound action potentials (CAPs), cochlear microphonics (CMs), and transiently evoked otoacoustic emissions (TEOAEs) were elicited by tone bursts (1, 2, 4 and 8 kHz) or non-linear clicks immediately following barotrauma. CAP threshold elevations were observed in 19 out of 25 cochleas, mainly at lower stimulus frequencies. Furthermore, CM and TEOAE thresholds were significantly increased, while CAP and CM amplitudes demonstrated reductions at all stimulus frequencies and intensities. CAP N1 latencies exhibited slight elongations at all stimulus frequencies and intensities. The regression coefficient between the mean CAP thresholds of four stimulus frequencies and TEOAE thresholds was statistically significant. Scanning electron microscopy (SEM) study of six electrophysiologically abnormal cochleas revealed stereocilia morphology in four, but no changes in two. We hypothesize that low pressure barotrauma can injure inner ear hair cells through an early threshold shift secondary to dislocation of the basement membrane.

Acoustic Stimulation↗

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↗

Cisplatin ototoxicity and the possibly protective effect of alpha-melanocyte stimulating hormone.

It is known that adrenocorticotrophic hormone (ACTH)-derived peptides, the so-called melanocortins, can reduce cisplatin-induced neurotoxicity. Recently, our group has found that cisplatin-induced ototoxicity can also be reduced or prevented by treatment with the synthetic melanocortin-like peptide, ORG 2766 (Hamers et al., 1994; De Groot et al., 1997). The present study was designed to investigate the possibly ameliorating effects of the physiologically more relevant naturally occurring neuropeptide alpha-melanocyte stimulating hormone (alpha-MSH) upon cisplatin ototoxicity and to compare its protective effects to those of ORG 2766. For eight consecutive days guinea pigs were treated with cisplatin at a concentration of either 1.5 mg/kg/day or 2 mg/kg/day. Animals were co-treated with either alpha-MSH (75 microg/kg/day), ORG 2766 (75 microg/kg/day), or a sham injection containing physiological saline. Electrocochleography and hair cell counts were performed. Treatment with 1.5 mg/kg/day cisplatin resulted in a large variability of the morphological and electrophysiological data, a variability that might have masked possible effects of ORG 2766 and alpha-MSH. Treatment with 2 mg/kg/day cisplatin caused less variable, severe reductions in the compound action potentials and cochlear microphonics combined with basal and middle-turn outer hair cell loss in five out of six animals. However, in the alpha-MSH co-treated groups, two out of six animals could be classified as normal, two animals as moderately affected and two animals as severely affected. In the ORG 2766 co-treated group we found three animals that were not affected and three animals that were severely affected. We conclude that the protective effects of alpha-MSH and ORG 2766 co-treatment are comparable and that alpha-MSH might be clinically useful in protecting against cisplatin-induced ototoxicity.

Action Potentials↗

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↗

Target sites of polymyxin B ototoxicity.

The present study was undertaken to determine the target sites of polymyxin B ototoxicity. This drug, at the concentration of 1 mM, was perfused through the scala tympani of the guinea pig cochlea, and cochlear microphonics and endocochlear potentials were monitored. Both cochlear potentials altered but in an independent manner. These findings indicated that not only the organ of Corti but also another tissue is involved in the ototoxicity produced. The best locus for this is the vascular stria.

Animals↗

The development of auditory function in the cochlea of the mongolian gerbil.

Cochlear microphonic (CM) potentials were recorded throughout the development of auditory function in the Mongolian gerbil. CM responses were first recorded at 12 days after birth (DAB), with thresholds exceeding 103 dB SPL. CM thresholds subsequently improved rapidly in a parallel fashion across the responsive frequency range, achieving adult levels by 18 DAB. There was no evidence from CM thresholds of a preferential rate of maturation for either the high or low frequency ranges. CM responses to suptrathreshold stimulation were also studied throughout development. At all responsive ages, CM input-output functions increased logarithmically to a saturating maximum value and then declined. Maximum CM responses increased continuously throughout development in a parallel fashion across all frequencies. The dynamic range of the CM input-output functions (the intensity interval from CM threshold to maximum CM value) also developed in a parallel manner across frequencies, but reached mature assymptotic values by 16 DAB. The results suggest that throughout the adult CM frequency range cochlear hair cell function develops simultaneously.

Age Factors↗