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Effects of noise and quinine on the vessels of the stria vascularis: an image analysis study.

Surface preparations of the stria vascularis from guinea pigs exposed to wide-band noise or intoxicated with quinine monohydrochloride dihydrate were studied by light microscopy and computerized image analysis in order to evaluate quantitatively the effects of these agents on two characteristics of the strial vasculature: vascular density and erythrocyte distribution. An image analyzer was used to measure the area of strial vessel lumen and erythrocyte distribution as a fraction of the total area of strial tissue under observation. The results demonstrate that changes in the strial vessels do occur in guinea pigs exposed to noise or given large doses of quinine. Localized vessel narrowings caused by swollen endothelial cells and possibly by contraction of pericytes were found in both experimental groups, but there was no apparent tonotopical relationship between these effects and the reduction in cochlear potentials. A significant reduction in the number of erythrocytes was found in all turns of the cochlea in both experimental groups. Although a significant difference in vascular density was found among turns of the cochlea in both experimental and control animals, there was no widespread change in vascular density as a result of either noise exposure or quinine treatment.

Animals↗

[The influence of endolymphatic sac surgery on cochlear function and structure in guinea pigs].

Experimental endolymphatic sac surgery was performed in 35 guinea pigs to evaluate the changes in cochlear function and structure caused by surgical manipulations which included incising the sac, aspirating the endolymph and probing the vestibular aqueduct. The experimental data showed that the changes in the cochlear potential, the auditory reaction threshold and the cochlear morphology in some guinea pigs were induced by these manipulations, especially aspirating the endolymph or probing the vestibular aqueduct. The possible mechanisms of the cochlear impairment may be damage caused by positive or negative pressure, the change in endolymphatic environment and the secondary inner ear hydrops. The experimental findings indicate that the cochlear function and structure can be affected by surgical manipulations, especially aspirating the endolymph or probing the vestibular aqueduct. Therefore, these manipulations should be avoided during the surgical procedure.

Animals↗

Potentiation of octave-band noise induced auditory impairment by carbon monoxide.

In previous studies from our lab, broadband noise induced hearing loss has been found to be potentiated by simultaneous carbon monoxide (CO) exposure. In the present study, octave-band noise induced auditory impairment was studied with the presence of CO at levels of 1500, 1200, 700, 500 and 300 ppm and zero (noise alone). Four octave-band noises (1.2-2.4, 2.4-4.8, 4.8-9.6 and 9.6-19.2 kHz) were used. Experimental subjects (rats) were grouped for the exposure (8 h) to each noise, CO and their combinations. The compound action potential (CAP) and cochlear microphonics (CM) were recorded 4 weeks after the exposure. The noise induced elevation of the CAP threshold and the CM iso-amplitude curve were potentiated by the simultaneous CO exposure when the CO level reached 500 ppm or higher. CO exposure alone had no effect on CAP or CM. The CO potentiation can occur in any frequency region depending on the noise band. The combined exposure can also induce threshold shifts in some cases in which both the noise and the CO alone did not cause threshold shifts. The size of the potentiation shown by CAP and CM was similar, indicating a possible origin of the CO potentiation from the damage to the outer hair cells. Interestingly, the hearing loss induced by noise alone gradually recovered (partially), but the hearing loss caused by the combined exposure did not. The potentiation may be due to the reduction of the cell's ability to repair noise induced damage by CO.

Animals↗

Time-varying alterations in the f2-f1 DPOAE response to continuous primary stimulation. II. Influence of local calcium-dependent mechanisms.

The distortion product otoacoustic emission (DPOAE) corresponding to the frequency f2-f1 displays stereotyped, time-varying amplitude alterations during continuous primary tone stimulation. The origin of these alterations is unknown; however, evidence that efferent neurons contribute little to the changes has been presented (Kujawa et al., 1994a, 1995; Lowe and Robertson, 1995). The present investigation examines the hypothesis that these alterations in f2-f1 amplitude are a reflection of local, Ca(2+)-dependent mechanisms involving the outer hair cell (OHC) response to sustained stimulation. Experiments were performed using urethane-anesthetized guinea pigs with sectioned middle ear muscles. Intracochlear perfusion was employed to reversibly lower perilymph Ca2+ levels and to introduce antagonists and agonists of L-type Ca2+ channels. Manipulations that lowered available Ca2+ (zero Ca2+ artificial perilymph; zero Ca2+ with BAPTA) or that blocked its entry into the cell via L-type Ca2+ channels (nimodipine) reduced, prevented or reversed the perstimulatory changes in f2-f1 DPOAE amplitude. These perilymph manipulations also reduced the overall amplitude of this distortion component while perfusion of an L-type Ca2+ channel agonist (Bay K 8644) increased its amplitude. Mg2+ did not substitute for Ca2+, suggesting that these are not merely divalent cation effects. Results are consistent with the hypothesis that continuous stimulation-related changes in f2-f1 DPOAE amplitude are sensitive to perilymph Ca2+ levels and to the function of L-type Ca2+ channels. However, nimodipine also reduced the endocochlear potential (EP) and Bay K 8644 increased the EP. The sensitivity of both the perstimulatory changes in f2-f1 DPOAE amplitude and the EP to the latter drugs leaves their site(s) of action unresolved.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗

Radial current flow and source density in the basal scala tympani.

Ionic movement between the scala media and scala tympani is modulated by acoustic stimulation. It underlies electrical currents in the fluids of these compartments and produces voltage gradients from which partial current-flow densities can be estimated. Radial voltage gradients were sampled in the first turn of the scala tympani of the guinea pig cochlea at known distances from the basilar membrane. Large potential gradients indicated significant current-flow densities near the organ of Corti with less flow near the lateral wall of the cochlea and over the spiral lamina. Current-source densities were highest within 100 micron of the organ of Corti. Current-source density analysis suggested that source-sink pairs can be detected from field observations in the scala tympani.

Acoustic Stimulation↗

[The endocochlear potential in experimental renal insufficiency].

Endocochlear Potential (EP) was measured in male Wistar rats under control conditions and renal failure produced by means of bilateral nephrectomy. Results show a statistically significant (p less than 0.01) decrease in EP measured in animals with renal failure. This finding is in accordance with the decrease in Na-K ATPase activity found in the cochlea and other structures in human and experimental kidney insufficiency.

Animals↗

Perilymphatic fistula in the guinea pig.

Clinical reports on perilymphatic fistulae (PLF) of the round window membrane (RWM) have shown different degrees of hearing loss. However, the hearing can also be entirely unaffected. Experimentally induced PLF of the RWM in animals showed results similar to those of the clinical reports, although some researchers have concluded that perforation of the RWM per se does not necessarily induce significant hearing loss. The purpose of the present study was to clarify if, and how, PLF of RWM in the guinea pig actually affects the auditory action potentials. During 1 h of observation following perforation of the RWM, the immediate and continuous effect of the PLF was evaluated. In more than 50% of the animals, different amounts of threshold shift were obtained. In another group of guinea pigs an attempt was made to clarify the findings by reducing the cerebrospinal fluid pressure before perforating the RWM.

Animals↗

Ototoxicity of kanamycin sulfate and the barriers in the inner ear.

The effect of kanamycin sulfate administered by three routes on the function of the stria vascularis was monitored electrophysiologically in guinea pigs. The three routes were intramuscular injection, perilymphatic perfusion, or endolymphatic perfusion. Neither systemic administration of 500 mg/kg of body weight per day for 7 to 12 days nor perilymphatic perfusion of 10(-3) M kanamycin affected the endocochlear dc potential (EP). However, with perfusion of kanamycin 10(-3) M in the endolymphatic space, the EP declined severely. Moreover, the decline in the EP was greater with higher concentrations of kanamycin in the endolymphatic perfusate. Furosemide given by each of the three routes produced an approximately equal decrease in the EP. The effects of kanamycin on the cells of the stria vascularis and the evidence for the perilymphatic-endolymphatic and blood-cochlear barriers are discussed.

Animals↗

A model of lateral line microphonic response to high-level stimuli.

The electrical potential recorded from the lateral line canal organs of fish in response to a sinusoidal vibratory stimulus consists of a microphonic component with frequency twice that of the stimulus plus a dc shift. This paper describes the behavior of both components as functions of stimulus frequency (from 100 to 400 Hz) and amplitude. The microphonic decreases with frequency, while the dc shift increases, and the two components have different input-output functions. An analytical model of hair cell electrical properties with an asymmetric saturating nonlinear conductance is presented that describes the behavior of both the microphonic and the dc shift.

Acoustic Stimulation↗

Stiffness, compliance, elasticity and force generation of outer hair cells.

Isolated outer hair cells (OHCs) were partially sucked into especially designed cell capillaries allowing an experimental reconstitution of the cells' electroanatomy. The experimental approach separated the apical from the basolateral parts of the cells thus forming an artificial scala media and scala tympani. Resistance between both was 121 +/- 42 M omega. A sequence of negative and positive pressures was applied to the basal cell pole allowing "pulling" or "pushing" of the sensory cell investigated. The resulting length changes together with the known pressures allowed the estimation of an actual longitudinal compliance of 354 +/- 35 m/N. Following "pulling" OHCs tended to resume their initial shape after the force had ceased to be effective indicating elastic distortions. The calculated elasticity modulus of OHCs amounted to 6.1 +/- 3.4 kN/m2. From this data an actual longitudinal whole cell stiffness of OHCs of 3 x 10(-3) N/m was calculated. Ultrasound scanning of immobilized OHCs identified the cuticular plate (CP) and a central core between CP and basal cell pole as structures contributing to the cells' acoustic stiffness. Changes of the potential differences between the artificial scala media and scala tympani resulted in active length changes following the command voltage with a slope of delta 1/(1 x U) = 0.055 V-1. Assuming the validity of Hooke's law, the force generation associated with the active length changes can be calculated since the compliance is known.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

[Experimental study of the intrauterine ototoxicity of dibekacin].

Previous works have demonstrated that mammals are more susceptible to aminoside ototoxicity during the period of auditory development. In order to test the intrauterine ototoxicity of dibekacin, an experiment was designated in pregnant guinea pigs intoxicated during the last three weeks of gestation (100, 60 and 30 mg/kg for 8 days). Newborn guinea pigs were tested electrophysiologically by recording cochlear potentials from the round window in response to filtered clicks of various frequency. No fetal ototoxicity due to dibekacin could be detected in the 36 animals tested. This study indicates that dibekacin has a very low ototoxic effect, even during the period of increased sensitivity to antibiotics. Comparatively, kanamycin has a major ototoxic effect when it is administrated at the same dosage during the same period of time.

Animals↗

Some organic acids attenuate the effects of furosemide on the endocochlear potential.

A series of organic acid transport inhibitors significantly reduced the endocochlear potential (EP) decline produced by furosemide in the chinchilla. Probenecid, sodium salicylate and penicillin G were much more effective than novobiocin, meclofenamate or diatrizoate. Inhibitors of organic base transport, choline and N-methyl nicotinamide, had no effect on the furosemide-induced drop of the EP. These findings suggest that at least part of furosemide ototoxicity may be mediated by organic acid transport.

Animals↗

[Experimental perilymphatic fistula: the electrocochleographic findings].

The aim of the present study was to evaluate the effect of experimental perilymphatic fistula on cochlear electrophysiological responses. Six albino guinea pigs, in which recording electrodes were implanted in order to record the electrocochleogram, were used. Experimental protocol investigated cochlear responses before the induction of the fistula in the round window membrane perforation and then two month later. Compound action potential thresholds increased immediately after perforation of the round window membrane. The thresholds rapidly recovered. This phenomenon was accompanied by clear-Out reduction in amplitude upon suprathreshold stimulation. This latter observation associated with a decrease in the amplitude of the threshold seems to be a specific audiologic sign of the fistula. The clinical implication are discussed.

Acoustic Stimulation↗

[Microlight-guided spectrophotometry of the cochlea].

BACKGROUND: Intraoperative measurements of local intracapillary hemoglobin oxygenation of the human cochlea via the round window membrane have been shown to be possible using the Erlangen microlight-guided spectrophotometer. The aim of the present study was to develop a new microlight guide suitable for measurements in the round window niche and to evaluate electrophysiologically the possible impact of the procedure on the cochlea. METHODS: Measurements were made for wavelengths of 450 to 900 nm at a total power of 5.3 mW. The exit diameter of the light guide was 200 microns and the angle used was 20 degrees. The recording depth was about 250 microns. The atraumatic character of the spectrophotometry was demonstrated by monitoring the compound action potential (CAP) threshold tuning curve from 1 to 34 kHz in ketanest-anesthetized guinea pigs. RESULTS: CAP thresholds remained constant (0.3 +/- 3.9 dB SPL) during 3 to 30 min of exposure to the light. CONCLUSIONS: These results suggest that the spectrophotometry may be useful as a new technique for intraoperative monitoring of intracapillary hemoglobin without causing physiological deterioration of the cochlea.

Animals↗

A study of the ototoxicity of deferoxamine in chinchilla.

Deferoxamine is a chelating agent used for the treatment of chronic iron overload in patients requiring long-term blood transfusions. Audiological testing of patients with B-thalassemia major and steroid-unresponsive Diamond-Blackfan anemia who were on long-term deferoxamine treatment indicated a possible ototoxic side-effect. In the present study we have investigated this potential toxicity to the cochlea of experimental animals by monitoring electrophysiological responses to sound and also by histological evaluation of the cochlea. In animals having chronic deferoxamine treatment, there were no significant changes in cochlear function or morphology. Data from acutely treated animals indicated an elevation of cochlear response thresholds together with morphological changes at the inner hair-cell level. However, these changes were highly correlated with the respiratory depression caused by an acute general toxicity, rather than a direct ototoxic effect of deferoxamine.

Animals↗

Photochemically induced double lateral wall lesions in the guinea pig cochlea.

OBJECTIVE: Multiple patches of atrophy have been reported in the stria vascularis (SV) in elderly persons with presbycusis The aim of this study was to investigate the correlation between sensorineural hearing loss and this strial condition. MATERIALS AND METHODS: We established a new animal model comprising two small lesions in the SV in the second turn of the cochlea by means of photochemical reaction. Using this model, we investigated morphological and physiological changes in the cochlea at 3, 7 and 14 days after SV damage. RESULTS: Scanning electron microscopy studies revealed that the strial cells between the two damaged areas of the SV remained intact, although the outer hair cells (OHCs) facing the intact SV area were damaged. Furthermore, damage to the first and second rows of OHCs gradually progressed throughout the 14-day observation period. The endocochlear potential (EP) measured at a point midway between the 2 lesions at 3 and 7 days was found to be significantly lower compared with control values, but had returned to a normal level at 14 days CONCLUSION: The reversible EP change and localized OHC loss seen in the present investigation may help to understand acute idiopathic or progressive sensorineural hearing loss.

Animals↗

Possible involvement of nitric oxide in the sensorineural hearing loss of bacterial meningitis.

Microperfusion of scala tympani with the NO donors, sodium nitroprusside (SNP) and S-nitroso-N-acetylpenicillamine (SNAP), produced marked depression of the compound action potential (CAP) and cochlear microphonic (CM) together with severe and widespread morphological damage to hair cells and supporting cells in the organ of Corti. In addition, direct perfusion of N-methyl-D-aspartate (NMDA) into scala tympani, which probably induces excess stimulation of NMDA receptors within the cochlea and which is known to lead to the release of NO, was found to elicit similar electrophysiological and structural lesions in the cochlea. Pre-perfusion of scala tympani with L-methyl arginine (L-MA), which inhibits the release of NO, or superoxide dismutase (SOD), an O2-scavenger, conferred marked protection upon the cochlea from the lesions caused by NO donors. These observations indicate that enhanced NO production is likely to be an important factor responsible for pathological insult of the cochlea. The possibility is discussed that this factor is involved in the chain of events leading to hearing loss caused by bacterial meningitis. Such hearing loss is a major sequela of bacterial meningitis in children.

Action Potentials↗

Ototoxic drugs and noise.

Drugs that produce tinnitus can be subdivided into those which produce temporary or permanent hearing loss and those which apparently do not cause any hearing loss. The tinnitus occurring with drugs of the first group is probably secondary to the hearing loss. However, most of the drugs that produce tinnitus without an accompanying hearing loss probably do so because of their effect on biogenic amines in the central nervous system and/or as an extension of their proconvulsant side-effects. A pre-existing cochlear impairment is the underlying factor in most patients who experience tinnitus. Not only can ototoxic drugs or high levels of noise produce cochlear impairment but the interaction of the two can place humans in more jeopardy than when exposed to either agent alone. Chloramphenicol has little ototoxic potential when administered systemically in humans. However, our studies show that when chloramphenicol is combined with noise exposure in rats, considerably more cochlear damage results than from the noise alone (chloramphenicol alone does no produce any cochlear damage). We are presently conducting more detailed studies of this ototoxic interaction to determine whether it occurs with other antibiotics (such as erythromycin) which are also commonly considered to have minimal ototoxicity.

Acoustic Stimulation↗