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Conclusions: Hydrostatic positive pressure and vasoconstrictor acidified the cochlear fluids, whereas the vasodilator made the fluids alkaline. CBF might play a role in regulating cochlea fluid pH., Objectives: Cochlea fluid pH is highly dependent on the HCO3(-)/CO2 buffer system. Cochlear blood flow (CBF) supplies O2 and removes CO2. It is speculated that cochlear blood flow changes might affect the balance of the HCO3(-)/CO2 buffer system in the cochlea. It is known that the elevation of inner ear pressure decreases the CBF, and local application of vasodilating or vasoconstricting agents directly to the cochlea changes the CBF. The purpose of this study was to elucidate the effect of positive hydrostatic inner ear pressure and application of a vasodilator and vasoconstrictor of cochlear vessels on the pH of the endolymph and perilymph., Methods: The authors performed animal physiological experiments on 30 guinea pigs. Hydrostatic positive pressure was infused through a glass capillary tube inserted into the scala tympani of the basal turn. The vasodilator, nitric oxide donor (sodium nitroprusside; SNP), and the vasoconstrictor, bupivacaine, were placed topically onto the round window of the guinea pig cochlea. Endolymph pH (pHe) and endocochlear potential (EP) were monitored by double-barreled ion-selective microelectrodes in the second turn of the guinea pig cochlea. During the topical application study, scala vestibuli perilymph pH (pHv) was also measured simultaneously in the second turn., Results: The application of hydrostatic positive pressure caused a decrease in pHe and EP. Positive perilymphatic pressure caused the endolymph to become acidic pressure-dependently. Application of 3.0% SNP evoked an increase in both the pHe and pHv, following by a gradual recovery to baseline levels. On the other hand, 0.5% bupivacaine caused a decrease in both the pHe and pHv. The EP during topical application showed slight, non-significant changes.

Conclusion: Our study demonstrates that the regulation of D2 receptors may be frequency specific. The reduction in cochlear microphonics (CM) and distortion product otoacoustic emission (DPOAE) amplitudes after perfusion with a D2 antagonist suggests that this receptor plays a role in the regulation of cochlear hair cell activation., Objectives: Dopaminergic terminals are subject to negative feedback from dopamine D2 receptors. In the present study we investigated whether the regulation of dopamine D2 receptor is frequency specific and evaluated changes in CM in guinea pig cochlea., Methods: A total of 30 male guinea pigs were randomly assigned to 3 groups and perfused with artificial perilymph (AP), AP containing ethanol (0.1%), or a D2 antagonist (L741626) for 2 h. In each group, compound action potentials (CAPs) evoked by a 1, 2, 4, 8, 16 or 24 kHz tone pip, CM evoked by 4 kHz tone bursts, and DPOAEs were measured before and 2 h after perilymphatic perfusion., Results: Perfusion with the D2 antagonist resulted in increased CAP thresholds compared with the other two groups at high frequencies (4, 8, 16, 24 kHz, p < 0.05); however, no significant increase was observed at low frequencies (1, 2 kHz, p > 0.05). There was a significant reduction in DPOAEs and CM amplitudes after the 2 h perfusion with the D2 antagonist. A CM input/output (I/O) function curve plotted with the stimulating level as input and the CM relative amplitude as output indicated obvious nonlinearity after the 2 h perfusion in all three groups.

Conclusion: Excess glutamate (Glu) exposure (20 mM) in the cochlear perilymph affects the physiological function of outer hair cells (OHCs) within a 2 h period and induces apoptosis in the modiolus spiral ganglion neurons (SGNs) in an apoptosis-inducing factor (AIF)-dependent manner., Objectives: To determine whether high-dose Glu affects the function of OHCs and whether it induces AIF- and caspase-3-dependent apoptosis in the cochlear SGNs., Methods: Perilymphatic perfusions of Glu (20 mM) and artificial perilymph (AP) solutions were performed in adult guinea pig cochleae. Both cochlear microphonics (CM) and electrical auditory brainstem response (eABR) were measured before and 2 h after perfusions. The hair cell morphologies were examined using transmission electron microscopy. The expression of two apoptotic indicators, AIF and caspase-3, was examined 8 h after perfusions., Results: In contrast to AP perfusions, the perfusion of 20 mM Glu caused significant reduction in the CM and eABR amplitudes. Inner hair cells (IHCs) after Glu perfusion were deformed and exhibited vacuolization in the postsynaptic region, whereas the OHC system appeared unaffected. AIF expression was detected in the nuclei of SGNs 8 h after Glu exposure, but the expression of caspase-3 was not shown in any cochlear tissues.

Objective: To examine the effects of gap junction blockers on the endocochlear potential (EP) and endolymphatic potassium concentration ([K(+)](e))., Material and Methods: The EP and [K(+)](e) were monitored using double-barreled ion-selective microelectrodes in the second turn of the guinea pig cochlea during perilymphatic perfusion., Results: When the perilymphatic scalae of the cochlea were perfused with artificial perilymph containing 10 mM n-heptanol the EP was decreased by -8.8+/-1.4 mV (n=10), and this was accompanied by a decline in the [K(+)](e) of -6.7+/-2.1 mM (n=6). Perilymphatic application of 10 mM hexanol also produced declines in both the EP and [K(+)](e). In control studies, perilymphatic perfusion with 10 mM ethanol showed no remarkable changes in either the EP or [K(+)](e). Anoxia during perfusion with heptanol resulted in the generation of a negative EP, similar to the situation in controls., Conclusions: A decline in the EP together with a lowering of [K(+)](e) induced by long-chain n-alkanols, which act as gap junction blockers, may be explained by an interruption in potassium ion transport related to a gap junction dysfunction.

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.

Nitric oxide (NO) has specifically been found to mediate the effects of excitatory amino acids in the central nervous system (CNS). Excitatory amino acids are the primary neurotransmitters at the cochlear hair cell afferent nerve synapse. Recent studies in our laboratory demonstrate that NO synthase is an active enzyme in the spiral ganglion cells of the cochlea. Given our current understanding of neurotransmission in the cochlea, it is reasonable to postulate that the actions of NO in cochlear neuronal tissue are similar to the actions of NO in the CNS, and that NO acts as a neurotransmitter/neuromodulator in the cochlea. In addition, NO is implicated as a mediator of excitotoxicity in the CNS and may therefore play a similar role in excitotoxicity in the cochlea. To further elucidate the role of NO in cochlear excitotoxicity, this study investigated the effects of 7-nitroindazole (7-NI), a competitive inhibitor of neuronal nitric oxide synthase, with regard to kainic acid (KA)-induced elevation of compound action potential (CAP) thresholds. KA is a conformationally restricted analog of glutamate with well-known excitotoxic effects on SGC's and previously described inhibitory actions on cochlear CAP thresholds. In anesthetized gerbils, CAP thresholds were recorded before and after cochlear perfusions with control solutions of artificial perilymph solution and test solutions of KA. 7-NI was administered i.p. prior to KA perfusion in an effort to block its depolarizing and toxic effects. Results showed that cochlear perfusion with KA caused significant elevation (p < 0.05) of the mean CAP threshold. This threshold shift was significantly reduced (p < 0.05) in animals pretreated with 7-NI. These results indicate that NO is involved in the toxic effects on CAP thresholds elicited by KA in the cochlea.

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.

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.

Local anaesthetics have been used intravenously and intratympanally to reduce tinnitus. In order to clarify its action in the periphery, we applied 0.5 mM tetracaine in the scala tympani in 18 cochleae and studied the effects on the receptor potentials. We used a temporal bone preparation of the guinea pig ear in vitro exposing the fourth cochlear turn where the cochlear microphonics (CM) and the summating potential (SP) were recorded. The perfusion was kept at a rate of 50 microliters/min. The frequency response of the cochlea was determined at the beginning of each experiment and the responses were recorded at the best frequency of the preparation. In another five cochleae an accumulated dose-response relationship was determined by increasing the tetracaine concentration in steps (50, 100, 300, 500, 1000 and 2000 microM), measuring the difference in amplitude of the receptor potentials. The CM decreased significantly (p < 0.001; mean 0.37 mV; SD 0.29). In 12 cochleae the SP was initially positive and did not increase significantly (p = 0.16; mean 0.07 mV; SD 0.16). In six cochleae the SP was initially negative and all changed polarity to positive and increased significantly (p < 0.05; mean 0.36 mV; SD 0.28). The effects on both the CM and the SP were reversible. Owing to the inter-individual variation between the cochleae the SP/CM ratio was determined and it increased significantly (p < 0.001; mean 0.18; SD 0.11). In the accumulated dose-response experiments the CM decreased significantly (p < 0.05) in a dose-dependent way, whereas the SP did not increase significantly. The SP/CM ratio increased significantly (p < 0.05) at 300 microM and 500 microM. We hypothesize that the peripheral tinnitus-reducing action of local anaesthetics is in part due to a reversal of the SP, but also to a reduction of the CM. The difference in effect of tetracaine on the receptor potentials, the CM and the SP, suggests that the SP is not dependent on the CM.

A previous study showed that systemic administration of erythromycin caused a reversible decline in the endocochlear and cochlear microphonic potentials. Those data were thought to suggest that erythromycin caused hearing loss by interference with ion transport processes in the stria vascularis. The present study was undertaken to test this hypothesis by measuring the effects of erythromycin perfused on either the apical or basolateral side on the transepithelial short circuit current (Isc), a measure of the K+ secretion rate. Isc was measured from preparations of strial marginal cells and the homologous vestibular dark cells in vitro with a micro-Ussing chamber. Erythromycin was found to have no effect when perfused on the apical side but to cause a reversible decrease in Isc when perfused on the basolateral side for both epithelia. These data are consistent with the notion that at least one ototoxic effect of erythromycin is the inhibition of K+ secretion in the inner ear.

Sensorineural hearing loss is a major sequela of the bacterial meningitis associated in particular with Streptococcus pneumoniae. Recent studies have shown pneumolysin, a toxin elaborated by S. pneumoniae, to be cytotoxic to the guinea pig cochlea. The mechanisms of this cytotoxicity are, however, not fully understood. In the present study this deleterious action of pneumolysin has been shown to be blocked by pretreating the cochlea with NG-methyl-L-arginine, a known inhibitor of nitric oxide synthesis. Furthermore, pretreatment of the cochlea with MK-801, an NMDA receptor antagonist, was also found to confer marked protection from the action of pneumolysin. This latter finding is consistent with previous reports that excess stimulation of NMDA receptors within the cochlea, an event known to lead to excess nitric oxide release, have similar effects on the cochlea as pneumolysin perfusion. It would therefore appear that nitric oxide may represent a significant link in the chain of events leading to the deafness of bacterial meningitis.

In the present study we investigated the influence of decreased endocochlear potential (EP) on acoustic trauma. Guinea pigs with decreased EP following i.v. administration of furosemide (FUR) and normal EP given physiological saline solution (PSS) i.v. instead of FUR were exposed to 2 kHz pure tone ranging from 110 to 130 dB SPL for 5 min. The input-output curves of the compound action potential (CAP) before acoustic overstimulation were compared with those at 2 h after the exposure. In 125 and 130 dB SPL exposure there was no difference in threshold shift between the FUR and PSS groups. In 115 and 120 dB SPL exposure, however, the threshold shift of the FUR group was significantly smaller than that of the PSS group. There was no significant difference between the two groups in 110 dB SPL exposure. These results indicate that the threshold shift of the CAP is mainly due to excessive vibration of the basilar membrane in the greater stimulus groups (125-130 dB SPL) but that the energy exhaustion of the hair cells to a certain extent participates in the threshold shift when the stimulus is milder (115-120 dB SPL). It is concluded that susceptibility to acoustic trauma of a milder intensity (115-120 dB SPL) is reduced when the energy consumption rate of the organ of Corti is decreased by EP suppression.

In order to further our basic understanding of the effects of lidocaine hydrochloride in the inner ear, cochlear potentials and blood flow (CBF) were assessed after intravenous (i.v.), anterior inferior cerebellar artery (AICA), and local round window (RW) lidocaine administrations in guinea pigs and rats. Lidocaine RW applications produced a dose dependent decrease in compound action potentials (CAP) and cochlear microphonics (CM). The sensitivity changes were more pronounced at high frequencies. These findings suggest that lidocaine has specific pharmacological action in the inner ear other than simple anesthesia of the auditory nerve. The basal turn endocochlear potentials (EP) were not altered by topical lidocaine, implicating altered organ of Corti function following local application of lidocaine. RW applications of lidocaine had no effect on CBF or systemic blood pressure (BP). I.v. infusions caused substantial reductions in BP. In the case of systemic infusions the percent changes in CBF were equal to and accountable by the BP changes. The microinfusions (50 mg/ml, 100 nl/min) through AICA produced a 30%, long lasting increase in CBF. However, neither systemic lidocaine nor AICA infusions had an effect on CAP or CM. These findings indicate that systemically given lidocaine may not cross the blood-cochlear barrier and that the cochlear electrophysiological effects due to lidocaine when given locally are partly mediated by direct influence on cochlear hair cell function; they also suggest that lidocaine-induced interference with active ion transport in the lateral wall or an influence on CBF are not contributing factors.

Presence of gentamicin (GM) in cochlear hair cells was detected by immunohistochemistry in guinea pigs (GPs) cochlea 1, 9 and 41 days after a 6-day treatment with GM at 60 mg/kg/day (s.c.). The number of GPs in each group was respectively 7, 12 and 6. Twelve other non-treated GPs served as controls. Cochlear function was measured, just before sacrifice, by VIIIth nerve compound action potential (CAP) audiograms. Functional and immunohistological evaluations were performed by two independent naïve observers respectively. Functional changes were minimal: only one out of the 25 treated GPs, from the 41-day group, showed significant threshold elevations on high frequencies. Meanwhile GM labelling was observed in most outer hair cells (OHCs) from the three rows of all the treated GPs, with radial and longitudinal gradients, and found similar in the 3 groups. These results 1) confirm that GM is significantly present in OHCs before the development of ototoxicity and 2) indicate that GM accumulates and is maintained inside the OHCs for very long periods of time, i.e. that its clearance from the hair cells, if any, would be very slow.

Potassium canrenoate (PC) is a diuretic with antialdosterone action, reducing the reabsorption of sodium in the efferent renal tubules. This drug has been reported to damage only the marginal cells of the stria vascularis in the cochlea. The perilymphatic space of the guinea pig cochlea was perfused with an artificial perilymph containing 5 x 10(-3) M potassium canrenoate. Following the onset of perfusion, the endocochlear dc potential (EP) gradually declined to around 10 mV but did not become negative even when the perfusion was continued. A similar decrease in EP was observed in kanamycin-deafened guinea pigs. When the respirator was turned off and perfusion discontinued, a large negative EP appeared during 5 min of anoxia in normal guinea pigs but not in the kanamycin-deafened guinea pigs. The decreased EP recovered to preanoxic level after resumption of ventilation. The cochlear microphonics (CM) also gradually declined in parallel with the EP. The summating potential (SP) showed only a minor change. The potassium ion activity in the endolymph decreased slightly but the sodium ion activity remained unchanged during perfusion. These findings suggest that the main target of the PC is the cells of the stria vascularis.

A reversible tinnitus and hearing loss have long been known to result from large doses of salicylate. Cochlear electrophysiology and otoacoustic emission studies suggest that the drug may interfere with outer hair cell electromotility. Exposure of isolated outer hair cells to sodium salicylate concentrations ranging from 0.05 to 10 mM reveals a dose dependent, reversible loss of turgidity and dimunition of electromotility. There was also a change in membrane conductance with salicylate superfusion that occurred later in time from the onset of shape and electromotility changes. There was no evidence of dose dependence for the change in membrane conductance, nor was the change reversible. The changes in shape and electromotility that we observe in vitro may impair cochlear partition movements in vivo and could account, at least in part, for the salicylate-induced hearing loss and effects on otoacoustic emissions.

Thirty guinea pig ears were studied to investigate the effect of endolymphatic hydrops on the cochlea. High K+ solution was injected into the scala media, and cochlear microphonics (CM) and endocochlear potential (EP) were observed before, during and after the injection. The CM amplitude decreased rapidly after injection, ending in a depressed plateau value. By contrast, EP remained almost unchanged. By changing the composition of the solution it was suggested that the effect of the injection was mechanical one, rather than biochemical. In three ears, spontaneous recovery of CM was observed during a relatively long interval after the injection. The meaning of these findings for the hearing loss in Meniere's disease is discussed.

The ototoxic interaction between the aminoglycoside antibiotics (streptomycin, kanamycin, etc.) and the loop-inhibiting diuretics (ethacrynic acid, furosemide and bumetanide) has been well documented. This interaction causes extensive destruction of the hair cells of the cochlea. Brummett et al. (1974) demonstrated that this interaction did not occur with the non-loop-inhibiting diuretics and kanamycin. The present study was undertaken to determine if antibiotics other than the aminoglycosides could produce the ototoxic interaction when combined with a loop-inhibiting diuretic. Three antibiotics-viomycin, capreomycin, and polymyxin B- when given with ethacrynic acid were found to produce cochlear hair cell damage that was similar to that produced by aminoglycoside antibiotics administered with ethacrynic acid. Therefore, the interaction appears to be specific to the loop-inhibiting diuretics but not specific for the aminoglycoside antibiotics.

Furosemide, a loop diuretic, reduces the endocochlear potential in guinea pigs. In our previous experiment using adult guinea pigs, glycerol was thought to open the blood-cochlea barrier and to help furosemide to reach its site of action in the stria vascularis. The present study was designed to determine whether or not the same potentiation by glycerol occurs in neonate guinea pigs. In one group, furosemide (10-30 mg/kg) was administered, while in another group, 50 v/v% glycerol (1 ml/kg) was administered 15 minutes prior to the injection of furosemide. Furosemide reduced the EP significantly more in neonates than in adults. This effect was not potentiated in the glycerol-pretreated group. From these findings, it seemed conceivable that the neonate blood-cochlea barrier still remains immature in some functions.

The perilymphatic space of the guinea pig was perfused in situ with artificial perilymph containing [32P] orthophosphate and 3H-glycerol while cochlear microphonic potentials (CM) were monitored. The perfusion of 10 mM gentamicin suppressed CM by 62% within 30 min. 32P-incorporation into phosphatidylinositol bisphosphate in the organ of Corti was decreased but distribution of 3H-glycerol in neutral lipids and phospholipids was not affected by gentamicin. The morphological evaluation included all structures lining the scala media, the spiral ligament, the basal membrane and the vestibular organs. Hair cells sometimes contained small intracellular 'precipitation' lines but, in general, ultrastructure of all tissues was essentially normal and no overt histopathological changes were evident. The observed biochemical changes should, therefore, represent early and primary actions of the drug. This confirms the hypothesis that an interaction with the acidic phospholipid, phosphatidylinositol bisphosphate, is an important step in the ototoxic mechanism of amino-glycoside antibiotics.

A change in endocochlear potential (EP) following furosemide injection was observed in regard to prior glycerol administration in two groups of guinea pigs. In one group, various doses of furosemide (20, 30, 40, 50 mg/kg) were injected, while in the other, glycerol (50 v/v %, 1 ml/kg) was injected prior to the furosemide (20, 30, 40 mg/kg) injection. In the glycerol-furosemide group, the decrease in EP was 40% greater than in the furosemide group. Therefore, glycerol was thought to potentiate the EP lowering action of furosemide. Such an effect of glycerol was assumed to be resulted by facilitating the access of furosemide to the site of action in the stria vascularis.

Endocochlear potential (EP) in the guinea pig was investigated under the influence of nifedipine and calcium chelating agents. The area from the scala tympani to the scala vestibuli was perfused with control and test solutions. EP decreased gradually after perfusion with the nifedipine solution, when the concentration was higher than 100 ng/ml. At a concentration of 200 ng/ml, EP decreased from +70 mV to +14 mV. At 1000 ng/ml, it decreased from +70 mV to +54 mV and stayed at this level during perfusion. It began to return to the initial level when perfusion with the control solution was recommenced. Cochlear microphonics (CM) also decreased with 200 ng/ml of nifedipine, but less markedly than EP. EGTA (10 mM) decreased EP from +80 mV to +67 mV. This change, however, was only transient and EP returned to the control level. EDTA (4 mM) had no significant effect on EP. These results suggest that Ca ions play a role in maintaining EP in a manner similar to that by which Ca modulates Na-K pump activity of the marginal cells in stria vascularis.

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.

Pregnant guinea pigs were treated with Kanamycin at three different stages of gestation (dating by method of post-partum ovulation). Twenty-nine newborn guinea pigs were tested electrophysiologically by recording the cochlear microphonic potential and the compound action potential from the round window in response to clicks and filtered clicks at 8,000 Hz. Six of the test animals showed the same electrophysiological changes as those found in adult mammals after Kanamycin intoxication. The results suggest a relationship between the ototoxicity of Kanamycin and the onset of auditory function. Cochlear potential and compound action potential were mostly affected when intoxication was performed during the last 15 days of gestation. This study confirms the results previously published by Uziel 1979.

This work was undertaken to study the ototoxicity of topically applied ethanol in quantitative terms. Using guinea pigs, ethanol was administered (1) on the round window for 10 min, (2) instilled in the middle ear cavity for 24 hours, and (3) perfused into the cochlear canal (into the scala tympani) at the rat of 10 microliter/min for 10 min. Cochlear microphonics from the electrode on the round window were recorded. The critical concentration (the maximum dilution ratio) of the ethanol that appears to be ototoxic in the experimental condition mentioned above was determined to be (1) 50%, (2) 10%, (3) 0.1% respectively. Using chinchillas, the effect of ethanol with round window application on the Endocochlear Potential (EP) was studied. Simultaneous recording of EP from the 1st and 3rd turn of the cochlea showed a more marked decline in EP in the 1st turn. 70% ethanol caused an irreversible, plateauing decline in EPO, while 35% ethanol caused a reversible decline in EP.

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.