Three years later: report on the state of well-being of patients with chronic tinnitus who underwent modified tinnitus retraining therapy.

Successful management of patients with chronic tinnitus is an important health issue. One of the tinnitus management strategies used at our Tinnitus Center is a combination of tinnitus retraining therapy (TRT) with physiotherapy and psychological management [called modified TRT (MTRT)]. We have used this type of management for over a decade and have described the protocol in detail elsewhere. In the present study, we wanted to determine the effect of MTRT on the well-being of tinnitus patients 3 years after treatment onset. One hundred and thirty patients with chronic tinnitus were assessed using psychometric instruments immediately before 7-day MTRT, immediately after the therapy and 3 years later. Patients with very severe tinnitus-related distress associated with major depression and a risk of suicide were excluded from this study. MTRT resulted in a sustained reduction of tinnitus-related distress. Moreover, the quality of life of patients had increased, as assessed by a separate questionnaire. The effect of MTRT was influenced by the degree of tinnitus-related distress and by the patients' age, the latter being gender dependent. Hearing loss and tinnitus duration had only a minor influence on the therapeutic effect. Taken together, we report a positive change in the state of well-being of patients with chronic tinnitus measurable with various psychometric instruments 3 years after the onset of MTRT.

Gender and chronic tinnitus: differences in tinnitus-related distress depend on age and duration of tinnitus.

OBJECTIVE: Conflicting data about the role of gender in tinnitus distress exist in the literature. In addition, little is known about gender differences regarding age and duration of tinnitus. Tinnitus was shown to be related to stress and impairment of coping, sense of coherence, and personal resources. There are known differences in the aforementioned psychological parameters between man and women or among different age groups. The authors hypothesized that this may also be true for patients with chronic tinnitus in addition to gender- and age-related differences in tinnitus annoyance. Therefore, using a large number of patients with chronic tinnitus, the authors analyzed pretherapeutic scores of tinnitus annoyance, perceived stress, proactive coping strategies, sense of coherence, and personal resources in addition to hearing loss and tinnitus pitch and loudness in respect to gender and age of the patients as well as duration of tinnitus. DESIGN: The study group included 607 female and 573 male patients who reported tinnitus for longer than 3 months. The age of the patients ranged from 17 to 81 years in both gender groups. Pretherapeutic scores of tinnitus annoyance, perceived stress, proactive coping strategies, sense of coherence, and personal resources as well as the degree of hearing loss and tinnitus pitch and loudness were analyzed. RESULTS: Irrespective of age and tinnitus duration, women were more annoyed by tinnitus and perceived more stress than men did. In addition, women scored lower than men in proactive coping, sense of coherence, and personal resources but had lower levels of hearing loss and tinnitus loudness than men did. The differences were small, but statistically significant. Analysis of three age groups revealed significant differences between older female and male patients. Tinnitus annoyance was stronger in the middle-age groups of women and men (45-59 years of age) than in younger patients and decreased again in older men (≥60 years of age), but not in older women. Women, but not men, had cognitive distress scores that progressed with age. Older women (≥60 years of age) reported more sleep disturbances than older men. Women had more somatic complaints and coped less efficiently than men, except for younger patients (<45 years of age). The scores of perceived stress decreased whereas scores of sense of coherence and self-efficacy increased in older men and women (≥60 years of age). However, women scored worse than men did in this age group. Hearing loss was found to be correlated with tinnitus loudness and age in both gender groups. The duration of tinnitus affected subjective hearing problems, intrusiveness of tinnitus, and proactive coping. This association was in part age-dependent. CONCLUSIONS: The authors found gender differences regarding tinnitus-related distress in patients with chronic tinnitus; however, these differences depended on age and in part on duration of tinnitus. Addressing these differences could result in improved, tailored therapy approaches. For instance, applying physical exercise and relaxation techniques could be of special help for older women to reduce their somatic complaints and sleep disturbances. Similarly, cognitive behavioral therapy could reduce their cognitive distress. Therapy for younger patients should in particular include stress management.

The impact of cochlear implantation on tinnitus, stress and quality of life in postlingually deafened patients.

Tinnitus is a common complaint in the candidates for cochlear implantation (CI). Tinnitus-related distress has often been measured in these patients using categorical ratings, which lack information about tinnitus severity, stress and health-related quality of life or their correlation. Here, using 4 validated questionnaires, we evaluated psychometric parameters and the quality of life of 32 postlingually deafened patients before and after CI. The data regarding pre-CI were collected retrospectively. Of all patients included in this study, 28 (87.5%) suffered from tinnitus before implantation. Following a mean of 24 months after surgery, these patients reported a significant decrease (39.2%) of tinnitus impairment, as measured by the Tinnitus Questionnaire. In none of the 28 patients has tinnitus worsened. Moreover, the 4 tinnitus-free patients remained so after the CI surgery. In addition, the implant supply resulted in 36.7% reduction in perceived stress and in 15.4% reduction in evasive coping. In addition, the focus on positive coping has improved by 12.3%, whereas the health-related quality of life improved by 53.4% in all patients. Tinnitus impairment and stress were reduced more strongly in patients who had initially higher scores. Interestingly, a significant correlation between the psychometric scores was found mainly after CI. Our results indicate that patients with higher tinnitus-related distress have a lower quality of life, lesser coping abilities and perceive more stress, but before implantation it is masked by deafness. We conclude that tinnitus-related screening of patients before and after CI is an important step in the identification of individuals who would benefit from specific fitting and/or tinnitus therapy after implantation.

Impact of laser eustachian tuboplasty on middle ear ventilation, hearing, and tinnitus in chronic tube dysfunction.

OBJECTIVES: Long-term Eustachian tube dysfunction (ETD) predisposes to various secondary middle ear diseases. Most surgical and prosthetical interventions on the Eustachian tube itself have proven to be ineffective, whereas middle ear surgeries treat the sequelae of ETD without major influence on the underlying tubal pathology. The purpose of our study was to evaluate the outcome of laser Eustachian tuboplasty (LETP) on tubal function and associated otological symptoms in topically anesthetized ETD patients with intact or perforated eardrums. DESIGN: In a prospective clinical investigation, outpatient LETP was carried out in 31 subjects with therapy-refractory chronic ETD. The study population comprised two groups: 16 patients with mesotympanic eardrum perforations diagnosed with noninflammatory chronic otitis media (COM) and 15 patients with intact eardrums including otitis media with effusion, adhesion processes, and dysfunctional pressure equalization. Clinical examination and data acquisition were performed 2 wks before LETP as well as 8 wks and 1 yr postoperatively. On COM patients, LETP was done at 10-wk intervals before the scheduled tympanoplasty. Assessment of clinical effectiveness was based on transnasal videoendoscopy, ear microscopy, tubal function tests (Valsalva maneuver and passive tubal opening), audio- and tympanometric measurements, and visual analog scales. Tansnasal, fiber-guided laser surgery was performed in contact mode using a semiconductor diode laser (λ = 830 nm, 4 W). We hypothesized that regulated laser ablation of hyperplastic mucosa at the epipharyngeal dorsal circumference of the tubal ostium could be effective in improving the associated symptoms such as dysfunctional pressure equalization, aural fullness, conductive hearing loss, and tinnitus. RESULTS: LETP resulted in persistent volume reduction of the posterior tubal circumference in all patients. Objective parameters revealed significant improvement of tubal function tests and middle ear ventilation in 62% of subjects after 8 wks (66% after 1 yr). Significant long-term reduction of conductive hearing loss was achieved in both patient groups. Besides, tinnitus loudness was significantly reduced in COM subjects after tympanoplasty. Visual analog scales showed very low values for intraoperative pain and discomfort and high scores for long-term overall patient satisfaction as well as improvement of the symptoms such as dysfunctional pressure equalization and aural fullness. Subjects with post-LETP Valsalva feasibility marked higher values for satisfaction and symptom improvement than patients without successful Valsalva maneuver. COM subjects scored higher in hearing improvement and satisfaction after LETP and successful tympanoplasty than patients with intact eardrums. CONCLUSIONS: Outpatient LETP seems to be a suitable, safe, easily applicable, and well-tolerated treatment option before (revision) tympanoplasties and in all investigated diseases developing from long-lasting pathologic middle ear ventilation. Minimally invasive shaping of the hyperplastic nasopharyngeal Eustachian tube under topical anesthesia seems to be effective in improving tubal function as well as the associated symptoms such as dysfunctional pressure equalization, aural fullness, and conductive hearing loss in otherwise therapy-refractory chronic ETD.

Long-term improvement in tinnitus after modified tinnitus retraining therapy enhanced by a variety of psychological approaches.

This work evaluates an enhanced tinnitus retraining therapy (TRT) for patients with chronic tinnitus based on different group therapeutic interventions in a day hospital setting. Therapy for chronic tinnitus is intended to improve the way patients cope with tinnitus by learning how to reduce tinnitus-induced impairments. Short-term and long-term changes in stress variables and tinnitus-related distress were investigated using 3 psychometric instruments. Patients received 7 consecutive days of a multidisciplinary therapy at the Charité University Hospital in Berlin. The data were assessed before and after therapy, either immediately or after 3, 6 or 12 months. As a control, we used scores of tinnitus patients from the waiting list, and compared these to the scores of the therapy group 3 months after the end of treatment. The main factors of the modified TRT were Jacobson's progressive muscle relaxation, physiotherapy, education via lectures and training of selective attention, as well as changes of appraisal, mental attitude and behavior towards tinnitus. The therapy resulted in a significant reduction in both short-term and long-term tinnitus-related distress and psychometric stress variables, with the latter being more reduced in patients with higher initial scores. Moreover, our study revealed differences in psychometric parameters concerning duration of tinnitus, age and gender, which may explain the different outcomes of therapy. The outpatient setting enables the patients to test, practice and transfer strategies into their everyday life.

Geldanamycin induces production of heat shock protein 70 and partially attenuates ototoxicity caused by gentamicin in the organ of Corti explants.

BACKGROUND: Heat shock protein 70 (HSP70) protects inner ear cells from damage and death induced by e.g. heat or toxins. Benzoquinone ansamycin antibiotic geldanamycin (GA) was demonstrated to induce the expression of HSP70 in various animal cell types. The aim of our study was to investigate whether GA induces HSP70 in the organ of Corti (OC), which contains the auditory sensory cells, and whether GA can protect these cells from toxicity caused by a common aminoglycoside antibiotic gentamicin. METHODS: To address these questions, we used the OC explants isolated from p3-p5 rats. As a read-out, we used RT-PCR, ELISA and immunofluorescence. RESULTS: We found that GA at the concentration of 2 microM efficiently induced HSP70 expression on mRNA and protein level in the OC explants. Confocal microscopy revealed that HSP70 induced by GA is expressed by hair cells and interdental cells of spiral limbus. Preincubation of explants with 2 muM GA prior to adding gentamicin (500 microM) significantly reduced the loss of outer but not inner hair cells, suggesting different mechanisms of otoprotection needed for these two cell types. CONCLUSION: GA induced HSP70 in the auditory sensory cells and partially protected them from toxicity of gentamicin. Understanding the molecular mechanisms of GA otoprotection may provide insights for preventative therapy of the hearing loss caused by aminoglycoside antibiotics.

Evaluation of vardenafil for the treatment of subjective tinnitus: a controlled pilot study.

BACKGROUND: Vardenafil (Levitra(R)) represents a potent and highly selective phosphodiesterase type 5 (PDE5) inhibitor, which is established for treatment of various diseases. There are several unpublished reports from patients stating that vardenafil has a considerable therapeutic effect on their concomitant tinnitus. This pilot study was conducted to specifically assess the effect of vardenafil in patients with chronic tinnitus. METHODS: This trial was based on a prospective, randomized, double-blind, placebo-controlled, parallel group design. Fourty-two consecutive subjects with mon- or binaural chronic tinnitus received 10 mg vardenafil (N = 21) or matching placebo tablets (N = 21) administered orally twice a day over a period of 12 weeks. Clinical examination and data acquisition took place at each visit: at baseline, after 4 weeks, after 12 weeks (end of treatment with study medication), and at non-medicated follow-up after 16 weeks. Assessment of clinical effectiveness was based on a standardized tinnitus questionnaire (TQ), the Short Form 36 health survey (SF-36), audiometric measurements (mode, pitch and loudness of tinnitus; auditory thresholds) and biomarkers of oxidative stress in patients' blood (malondialdehyde, protein carbonyl, homocysteine and total antioxidative status). Therapeutic efficacy was evaluated by comparison of subjective and objective parameters with baseline data between both treatment groups (ANCOVA). RESULTS: Vardenafil had no superior efficacy over placebo in the treatment of chronic tinnitus during this study. The primary efficacy criterion 'TQ total score' failed to demonstrate significant improvement compared to placebo. Subjective reports of TQ subscales and general quality of life areas (SF-36), objective audiometric examinations as well as investigated biomarkers for oxidative stress did not reveal any significant treatment effects. The safety profile was favorable and consistent with that in other vardenafil studies. CONCLUSION: Although hypoxia and ischemia play a special role in the pathogenesis of tinnitus, the PDE5-inhibitor-induced increase of nitric oxide-mediated vasodilatation exerted no specific influence on tinnitus symptomatology. Considering the unclear risk of rarely associated hearing impairment, systemic application of vardenafil or other PDE5 inhibitors prove to be not appropriate for therapy of chronic tinnitus.

Expression of apoptosis-related genes in the organ of Corti, modiolus and stria vascularis of newborn rats.

Cell death in the inner ear tissues is an important mechanism leading to hearing impairment. Here, using microarrays and real-time RT-PCR we analyzed expression of selected apoptosis-related genes in rat's inner ear. We determined the gene expression in tissues freshly isolated from neonatal rats (3-5 days old) and compared it to that of explants cultured for 24 h under normoxic or hypoxic conditions. For the analyses, we used pooled samples of the organ of Corti (OC), modiolus (MOD) and stria vascularis (SV), respectively. We observed region-specific changes in gene expression between the fresh tissues and the normoxic culture. In the OC, expression of the proapoptotic genes caspase-2, caspase-3, caspase-6 and calpain-1 was downregulated. In the MOD, the antioxidative defense SOD-2 and SOD-3 were upregulated. In the SV, caspase-2, caspase-6, calpain-1 and SOD-3 were downregulated and SOD-2 upregulated. We speculate that these changes could reflect survival shift in transcriptome of inner ear explants tissues under in vitro conditions. With the exception of SOD-2, hypoxic culture conditions induced the same changes in gene expression as the normoxic conditions indicating that culture preparation is likely the dominating factor, which modifies the gene expression pattern. We conclude that various culture conditions induce different expression pattern of apoptosis-related genes in the organotypic cochlear cultures, as compared to fresh tissues. This transcriptional pattern may reflect the survival ability of specific tissues and could become a tempting target for a pharmacological intervention in inner ear diseases.

Up-regulation of prestin mRNA expression in the organs of Corti of guinea pigs and rats following unilateral impulse noise exposure.

Prestin is the motor protein of the outer hair cells (OHCs) and is required for both their electromotility and for cochlear amplification. We investigated the prestin mRNA expression in guinea pigs and rats in relation to the degree of noise-induced hearing loss (NIHL) induced by unilateral impulse noise exposure (167dB peak SPL) for 2.5-5 min. Distortion product otoacoustic emissions (DPOAE) and auditory brainstem responses were recorded before and one week post exposure. Prestin mRNA was examined by quantitative reverse transcription-polymerase chain reaction. Either the whole organs of Corti or the apical, middle and basal parts were examined separately. The specimens were pooled and grouped according to the degree of NIHL measured in the exposed ears. In rats, the number of hair cells was counted. A clear base-to-apex gradient in the prestin mRNA expression was found to exist in guinea pig and rat controls. In both species, there was an increase in the number of prestin RNA transcripts at a mean NIHL of about 15-25 dB indicating an up-regulation in the remaining intact cells. In rats, this degree of NIHL corresponded to an OHC loss of about 40%. Interestingly, the contralateral ears also revealed an up-regulation of prestin mRNA accompanied by significant DPOAE improvements.

Tacrolimus: a new option in therapy-resistant chronic external otitis.

OBJECTIVE: To evaluate the efficacy of the novel topical immune modulator tacrolimus in chronic uninfectious otherwise therapy-resistant external otitis (EO). STUDY DESIGN: Prospective clinical study. PATIENTS AND METHODS: There were 53 patients aged 5 to 83 years. An ear wick containing 0.1% tacrolimus ointment (Protopic) was inserted into the external auditory canal every 2nd to 3rd day. Altogether, the wick was changed three times. The pre-, intra- and posttherapeutic state of the clinical parameters otalgia, edema, otorrhea, erythema, pruritus, and desquamation was rated by means of a 6-point score system. Treatment efficiency was evaluated on the basis of follow-up investigations at 3-month intervals, a standardized findings sheet, and photograph documentation. RESULTS: The short-term results showed a clear improvement in 85% of the patients and significant reductions of the severity levels for all clinical parameters investigated (P < .001). Concerning the long-term results, a one-time treatment cycle led to complete healing in 46% of the patients throughout a follow-up of 10 to 22 months. Of the patients, 54% had recurrent EO events with significantly extended mean symptom-free intervals. Reapplied tacrolimus treatment patterns attenuated the relapsing course of disease and significantly reduced the number of EO episodes. Within the observation period, no relevant side effects were observed, except for a local feeling of heat, occasional skin burning, and itching. CONCLUSIONS: The topical application of 0.1% tacrolimus ointment in the outer ear canal appears to be an effective and well-tolerated new option in corticosteroid-free treatment of chronic therapy-resistant EO.

Topical tacrolimus treatment for chronic dermatitis of the ear.

Recurrent exacerbation in chronic recalcitrant external otitis (EO) often warrants multidisciplinary treatment and collaboration with a dermatologist. The aim of this pilot study was to ascertain the efficacy of topical tacrolimus ointment application in chronic, non-infectious and therapy-resistant EO. In a prospective clinical study, the efficacy of tacrolimus ointment 0.1% was examined in 53 patients with therapy-refractory chronic EO of confirmed non-infectious etiology. Clinical examination took place prior to treatment (V1), at the end (V2) and during follow-up investigations (V3) of 28 patients over 10-22 months. Patients were evaluated for the symptoms otalgia, edema, otorrhea, erythema, pruritus and desquamation on a 6-point scale. The short-term results after topical application of tacrolimus (V2) showed a clear improvement in 85% of the patients (N = 45) and significant drop in severity scores for all clinical parameters (p < 0.001). The long-term follow-up studies (V3) revealed that a one-time treatment cycle led to complete remission in 46% of patients (N = 28). The remaining 54% had recurrent EO events, however, with significantly longer symptom-free intervals. Within the observation period, no relevant local or systemic side effects were observed, except for occasional skin burning, stinging, or itching. This interdisciplinary study between dermatologists and ENT specialists clearly demonstrates that the topical application of 0.1% tacrolimus ointment is an effective and well-tolerated new option in the treatment of chronic recalcitrant EO. Furthermore, it shows that dermatologists, with their experience in topical immunomodulatory therapy, can make valuable contributions to the treatment of inflammatory disorders in other medical fields.

Coenzyme Q10 does not protect cochlear hair cells from death in the ischemic organotypic culture.

OBJECTIVE: To evaluate in vitro the effect of coenzyme Q10 (CoQ(10)) on ischemia-induced hair cell death. STUDY DESIGN: Organotypic cochlear cultures of newborn rats were subjected to ischemia with and without CoQ(10). RESULTS: Addition of CoQ(10) has not prevented HC loss. CONCLUSION: CoQ(10) seems to protect against only certain modes of cell death.

A pilot clinical trial of the effects of coenzyme Q10 on chronic tinnitus aurium.

OBJECTIVE: To determine the short-term effects of coenzyme Q10 (CoQ10) on the antioxidative status and tinnitus expression in patients with chronic tinnitus aurium. STUDY DESIGN: A 16-week prospective nonrandomized clinical trial (n = 20). Tinnitus and Short Form-36 Questionnaires (TQ/SF-36) were evaluated together with the plasma concentrations of CoQ10, malondialdehyde, and the total antioxidant status. RESULTS: The mean plasma CoQ10 concentration rose under external CoQ10 supply and remained elevated after medication stopped without overall effects on the tinnitus score. However, in a subgroup of 7 patients with low initial plasma CoQ10 concentration and significant increase in the plasma CoQ10 level, a clear decrease in the TQ score was observed. CONCLUSION: In patients with a low plasma CoQ10 concentration, CoQ10 supply may decrease the tinnitus expression. SIGNIFICANCE: This is the first study to examine the effect of CoQ10 in chronic tinnitus aurium.

Recombinant human erythropoietin prevents ischemia-induced apoptosis and necrosis in explant cultures of the rat organ of Corti.

This study was designed to evaluate the effect of recombinant human erythropoietin (rhEPO), insulin-like growth factor-1 (rhIGF-1) and epidermal growth factor (rhEGF) on ischemia-induced hair cell loss in an organotypic cochlea culture. The apical, middle and basal parts of the organs of Corti (newborn rat, postnatal days 3-5) were exposed to ischemia (3.5 h) in glucose-free artificial perilymph (pO2 10-20 mmHg) with or without growth factors. Controls were exposed to normoxia. Twenty-four hours after the onset of ischemia, the cultures were stained using tetramethyl rhodamine isothiocyanate (TRITC) phalloidin (hair cells), propidium iodide (membrane integrity) and apoptosis detection kit (DNA-fragmentation). Ischemia (3.5 h) induced a hair cell loss of 20 and 40% in the middle and basal cochlear parts, respectively, and an increase of the numbers of PI-stained and DNA-fragmented nuclei (controls 0-1, ischemia 4-7 nuclei/100 microm). The basal part was more affected than the apical one. rhEPO and rhIGF-1 significantly attenuated the ischemia-induced hair cell loss by reducing processes involved in apoptosis and necrosis. rhEPO has been in clinical use for more than a decade and found to be well tolerated. Therefore, rhEPO could be an effective drug for the prevention of hearing loss via a hair cell protective mechanism.

High potassium concentrations protect inner and outer hair cells in the newborn rat culture from ischemia-induced damage.

Several studies indicate that an increase in the extracellular potassium (K+) concentration is a factor exerting a damaging effect on cochlear hair cells (HCs). The present study was designed to examine the effects of high extracellular K+ concentrations on the HCs under normoxic and ischemic conditions. Organotypic cultures of the organ of Corti of newborn rats were exposed to normoxia and ischemia at K+ concentrations of 5-70 mM in artificial perilymph for 3-4h. The number of IHCs and OHCs in the apical, medial and basal parts of the cochlea were counted 24h later. The work resulted in two main findings: (1) extracellular K+ concentrations of 30-70 mM had no effect on the HCs under normoxic conditions; (2) under ischemic conditions, a clear HC loss, mainly in the medial and basal cochlear parts, was observed at 5 mM K+ as previously reported. In contrast, a high extracellular K+ concentration strongly attenuated the HC loss. This effect nearly completely disappeared by the addition of both eosin, an inhibitor of the plasma membrane calcium ATPase (PMCA), and linopirdine, an inhibitor of the KCNQ4 channel, indicating that a normal activity of the PMCA and the KCNQ4 channels are key factors for HC survival under ischemia and depolarizing conditions.

A model of peripherally developing hearing loss and tinnitus based on the role of hypoxia and ischemia.

The incidence of sensorineural hearing loss often caused by direct damage to the cochlear hair cells is by far more frequent and more serious than disorders affecting the external ear or the middle ear. Mechanisms that are discussed to be relevant for the genesis of tinnitus and acquired hearing impairment are hair cell loss, signal transduction disturbances in the region of the outer and inner hair cells and the spiral ganglion, impairment of cochlear blood flow, mechanical disturbance, and hypoxia and ischemia. The present model surveys the possible cellular and molecular biological causes of peripherally developing hearing loss and tinnitus. In particular, the paper discusses the roles of hypoxia and ischemia in the cochlea and in the etiology of the neurosensory types of tinnitus. Peripheral origins of hearing disturbances and tinnitus may be: (a) damage to the stereocilia and the tip links, (b) dysfunction of potassium channels or (c) modification of the glutamate release. Moreover, the hypoxia inducible factor-1 may have an important role to play as a key transcription factor in the cells' adaptation to hypoxia and ischemia. An impairment of the cochlear blood flow may be induced by the expression of target genes like nitrogen monoxide synthase and endothelin-1 resulting in tinnitus. The paper discusses consequences resulting from the present model for the medical treatment of peripherally developing tinnitus and hearing loss.

Argon protects hypoxia-, cisplatin- and gentamycin-exposed hair cells in the newborn rat's organ of Corti.

During the last few years, an important protective effect of the noble gas xenon against neuronal hypoxic damage was observed. However, argon (Ar), a gas from the same chemical group, but less expensive and without anesthetic effect at normobaric pressure, has not been studied in terms of possible biological effects on cell protection. Ar was tested for its ability to protect organotypic cultures of the organ of Corti from 3-5 day old rats against hypoxia, cisplatin, and gentamycin toxicity. Cultures were exposed to nitrogen hypoxia (5% CO2, 95% N2), Ar hypoxia (5% CO2, 95% Ar) or normoxia for 30 h. Ar protected the hair cells from hypoxia-induced damage by about 25%. Ar-oxygen (O2) mixtures (21% O2, 5% CO2, 74% Ar) had no effect on the hair cell survival. Cisplatin (7.5-25 microM) and gentamycin (5-40 microM) exposed in medium under air damaged the hair cells in a dose-dependent manner. The exposure of cisplatin- and gentamycin-treated cultures to the Ar-O2 atmosphere significantly reduced the hair cell damage by up to 25%. This protective effect of Ar might provide a new protective approach against ototoxic processes.

Susceptibility of the hair cells of the newborn rat cochlea to hypoxia and ischemia.

Hypoxia and ischemia are thought to be important pathogenetic factors in bringing about hearing loss. In order to study the effect of these determinants on the loss of inner and outer hair cells (IHCs/OHCs), we used an in vitro hypoxia and ischemia model of the newborn rat cochlea. The specimens of the organ of Corti were exposed either to hypoxia (10-20 mm Hg) or to normoxic glucose deprivation or to both (ischemia) in artificial perilymph for different exposure periods. The number of IHCs and OHCs was counted and the hair cell loss was compared to controls. Normoxic aglycemia did not cause significant hair cell loss as compared to controls. Hypoxia and ischemia led to hair cell loss in a dose-dependent manner, with the loss in the ischemia groups found to be markedly higher than that in the hypoxia groups. Hypoxia resulted in a mean loss of 8% OHC and of 14% IHC after an 8-h exposure. Ischemia increased the loss to 19% OHC and 39% IHC after the same exposure period of 8 h. Our findings suggest that IHCs are more susceptible to hypoxia/ischemia than OHCs.

Therapeutic effect of magnesium on noise-induced hearing loss.

This study examined the therapeutic effect of magnesium (Mg) on noise trauma in anesthetized guinea pigs exposed to an impulse noise series (1/s) of Lpeak 167 dB (Leq,1s 127 dB) for 38 min. The permanent hearing threshold shift (PTS) was measured 1 week post-exposure, using auditory brain stem response audiometry (frequency range, 0.5-32 kHz). The total Mg concentrations of perilymph, cerebrospinal fluid and plasma were analyzed by atomic absorption spectrometry. In a first series, animals maintained on physiologically low Mg received subcutaneous injections of either different Mg doses (0.11-0.33 mmol MgSO4/100 g per day) for 3 days and drinking water with an additive of 39 mmol MgCl2/l for 1 week or saline as a placebo and tap water alone. The treatment began immediately after the impulse noise exposure. The dose of 0.29 mmol Mg/100 g per day was found to be most effective and reduced the hearing loss by 13-20 dB compared to placebo. The PTS and the perilymph Mg level showed a close negative correlation, suggesting that the intracochlear Mg level plays an important role in bringing about these protective effects. In a second series, we tested the therapeutic efficacy as a function of the post-exposure time of onset of the optimal Mg treatment (1 min, 2 and 4 hours), using normal Mg animals. The therapeutic effect decreased with the length of time elapsed between the end of exposure and the beginning of treatment. In a parallel scanning electron microscopic test, we also found a Mg-related difference in the susceptibility of hair cell stereocilia to impulse noise exposure.

Preventing noise induced otoacoustic emission loss by increasing magnesium (Mg2+) intake in guinea-pigs.

This study aimed to explore the effects of increased Mg2+ intake on the activity of the outer hair cells as manifested in Click and Distortion Evoked Otoacoustic Emissions (CEOAEs; DPOAEs) in 25 animals. Thirteen animals were fed with high Mg2+ intake (39 mmol Mg2+/l in drinking water) and 12 without the Mg2+ additive. The OAE amplitudes and frequency ranges as well as the DPOAE thresholds were affected significantly less by noise exposure in the animals fed Mg2+-enriched water. Following the exposure, the auditory recovery was faster in the high than the low Mg2+ animals (controls). In addition, a relationship was found between the Mg2+ level and the emission loss. The post-exposure measures may result from the effect of Mg2+ on cochlear metabolic processes and vascular microcirculation. The results demonstrate that pre-existing low Mg2+ levels will exacerbate noise induced hearing loss (NIHL), and increased Mg2+ intake provides a significant biological cochlear protective effect.