Influence of sound-conditioning on noise-induced susceptibility of distortion-product otoacoustic emissions.

Cochlear damage caused by loud sounds can be attenuated by "sound-conditioning" methods. The amount of adaptation for distortion product otoacoustic emissions (DPOAEs) measured in alert rabbits previously predicted an ear's susceptibility to a subsequent noise exposure. The present study investigated if sound-conditioning influenced the robustness of such DPOAE adaptation, and if such conditioning elicited more protection by increasing the amount of DPOAE adaptation. Toward this end, rabbits were divided into two study groups: (1) experimental animals exposed to a sound-conditioning protocol, and (2) unconditioned control animals. After base-line measures, all rabbits were exposed to an overstimulation paradigm consisting of an octave band noise, and then re-assessed 3 weeks post-exposure to determine permanent changes in DPOAEs. A major result was that prior sound-conditioning protected reductions in DPOAE levels by an average of 10-15 dB. However, DPOAE adaptation decreased with sound-conditioning, so that such conditioning was no longer related to noise-induced reductions in DPOAEs. Together, these findings suggest that sound-conditioning affected neural pathways other than those that likely mediate DPOAE adaptation (e.g., medial olivocochlear efferent and/or middle-ear muscle reflexes).

Adaptation of distortion product otoacoustic emissions predicts susceptibility to acoustic over-exposure in alert rabbits.

A noninvasive test was developed in rabbits based on fast adaptation measures for 2f1-f2 distortion-product otoacoustic emissions (DPOAEs). The goal was to evaluate the effective reflex activation, i.e., "functional strength," of both the descending medial olivocochlear efferent reflex (MOC-R) and the middle-ear muscle reflex (MEM-R) through sound activation. Classically, it is assumed that both reflexes contribute toward protecting the inner ear from cochlear damage caused by noise exposure. The DP-gram method described here evaluated the MOC-R effect on DPOAE levels over a two-octave (oct) frequency range. To estimate the related activation of the middle-ear muscles (MEMs), the MEM-R was measured by monitoring the level of the f1-primary tone throughout its duration. Following baseline measures, rabbits were subjected to noise over-exposure. A main finding was that the measured adaptive activity was highly variable between rabbits but less so between the ears of the same animal. Also, together, the MOC-R and MEM-R tests showed that, on average, DPOAE adaptation consisted of a combined contribution from both systems. Despite this shared involvement, the amount of DPOAE adaptation measured for a particular animal's ear predicted that ear's subsequent susceptibility to the noise over-exposure for alert but not for deeply anesthetized rabbits.

Time-domain demonstration of distributed distortion-product otoacoustic emission components.

Distortion-product otoacoustic emissions (DPOAEs) were measured in rabbits as time waveforms by employing a phase-rotation technique to cancel all components in the final average, except the 2f1-f2 DPOAE. Subsequent filtering allowed the DPOAE waveform to be clearly visualized in the time domain. In most conditions, f2 was turned off for 6 ms, which produced a gap so that the DPOAE was no longer generated. These procedures allowed the DPOAE onset as well as the decay during the gap to be observed in the time domain. DPOAEs were collected with L1 = L2 = 65-dB sound pressure level primary-tone levels for f2/f1 ratios from 1.25 to 1.01 in 0.02 steps. Findings included the appearance of complex onsets and decays for the DPOAE time waveforms as the f2/f1 ratio was decreased and the DPOAE level was reduced. These complexities were unaffected by interference tones (ITs) near the DPOAE frequency place (fdp), but could be removed by ITs presented above f2, which also increased DPOAE levels. Similar outcomes were observed when DPOAEs were measured at a sharp notch in the DPOAE level as a function of the f2 primary tone frequency, i.e., DP-gram. Both findings were consistent with the hypothesis that the DPOAE-ratio function, and some notches in the DP-gram, are caused by interactions of distributed DPOAE components with unique phases.

Characterizing distortion-product otoacoustic emission components across four species.

Distortion-product otoacoustic emissions (DPOAEs) were measured as level/phase (L/P) maps in humans, rabbits, chinchillas, and rats with and without an interference tone (IT) placed either near the 2f(1)-f(2) DPOAE frequency place (f(dp)) or at one-third of an octave above the f(2) primary tone (1/3-oct IT). Vector differences between with and without IT conditions were computed to derive a residual composed of the DPOAE components removed by the IT. In humans, a DPOAE component could be extracted with the expected steep phase gradient indicative of reflection emissions by ITs near f(dp). In the laboratory species, ITs near f(dp) failed to produce any conclusive evidence for reflection components. For all species, 1/3-oct ITs extracted large DPOAE components presumably generated at or basal to the IT-frequency place that exhibited both distortion- and reflection-like phase properties. Together, these findings suggested that basal distortion components could assume reflection-like phase behavior when the assumptions of cochlear-scaling symmetry, the basis for shallow phase gradients for constant f(2)/f(1) ratio sweeps, are violated. The present results contradict the common belief that DPOAE components associated with steep or shallow phase slopes are unique signatures for reflection emissions arising from f(dp) or distortion emissions generated near f(2), respectively.

Evidence for basal distortion-product otoacoustic emission components.

Distortion-product otoacoustic emissions (DPOAEs) were measured with traditional DP-grams and level/phase (L/P) maps in rabbits with either normal cochlear function or unique sound-induced cochlear losses that were characterized as either low-frequency or notched configurations. To demonstrate that emission generators distributed basal to the f(2) primary-tone contribute, in general, to DPOAE levels and phases, a high-frequency interference tone (IT) was presented at 1/3 of an octave (oct) above the f(2) primary-tone, and DPOAEs were re-measured as "augmented" DP-grams (ADP-grams) and L/P maps. The vector difference between the control and augmented functions was then computed to derive residual DP-grams (RDP-grams) and L/P maps. The resulting RDP-grams and L/P maps, which described the DPOAEs removed by the IT, supported the notion that basal DPOAE components routinely contribute to the generation of standard measures of DPOAEs. Separate experiments demonstrated that these components could not be attributed to the effects of the 1/3-oct IT on f(2), or DPOAEs generated by the addition of a third interfering tone. These basal components can "fill in" the lesion estimated by the commonly employed DP-gram. Thus, ADP-grams more accurately reveal the pattern of cochlear damage and may eventually lead to an improved DP-gram procedure.

An intracochlear DP-gram: Proof of principle in noise-damaged rabbits.

Distortion-product otoacoustic emissions (DPOAEs) can be used to assess cochlear damage and are often evaluated by generating a DP-gram in which 2f1-f2 DPOAE levels are plotted as a function of the higher-frequency primary at f2. DPOAEs are derived from the reverse propagation of distortion-product (DP) wavelets from their intracochlear sites of generation to emerge as measurable acoustic signals in the outer ear canal. However, at least, some of these same wavelets also propagate within the cochlea in the normal forward direction to the DP-frequency (fdp) place, where they appear as intracochlear distortion products (iDPs). Depending on several factors, especially, the extent to which DP wavelets add or cancel with each other in phase, one might expect iDPs to differ from DPOAEs in their ability to map the frequency pattern of cochlear damage. In the present study, the behavior of 2f1-f2 iDPs was inferred by interacting a probe tone (f3) with the iDP of interest to produce a 'secondary' DPOAE (i.e., DPOAE2ry), which was then used to infer the level of 2f1-f2 iDPs as a function of the f2-test frequency, thus, constituting a newly developed iDP-gram. To determine the feasibility of and potential applications for the iDP-gram procedure, noise-induced cochlear damage was assessed in two 'test' rabbits, one of which exhibited a well-defined punctate loss in their DP-gram, while the other exhibited a broader V-shaped loss. To validate the iDP-gram procedure, standard DP-grams were simultaneously collected and compared to their iDP-gram counterparts. Cochlear damage was independently assessed using auditory brainstem responses (ABRs) describing threshold-shift patterns to which both DP-gram types could be compared. Each DP-gram variety, to some extent, was able to detect a punctate loss in one rabbit and a broader V-shaped loss in the other. For the punctate-loss subject, the standard DP-gram showed a more generalized loss across test frequencies, while iDP-grams showed several localized notches superimposed on the generalized-loss pattern. In general, for the V-shaped loss pattern, both DP-gram types performed very well at detecting the large loss, with the lower primary-tone levels being most sensitive. At the narrow primary-tone ratios of f2/f1=1.05, standard DP-grams were unable to detect either loss pattern, while for the punctate loss, they paradoxically showed enhancement. Notably, the simultaneously collected iDP-grams performed favorably at the narrow-ratio setting, which is consistent with the notion that DPs travelling toward the 2f1-f2 fdp place are not subject to the cancellation of wavelets typical for narrow primary-ratio conditions that can confound measures of DPs moving towards the ear canal to emerge as DPOAEs.

Steep and shallow phase gradient distortion product otoacoustic emissions arising basal to the primary tones.

Distortion product otoacoustic emission (DPOAE) level/phase maps were collected in humans with and without an interference tone (IT) near the DPOAE frequency place (f(dp)) at primary-tone levels of 75 dB SPL. A DPOAE component with the expected steep phase gradient could be extracted at f(dp), however, considerable vertical-phase banding, presumably indicative of reflection emissions, remained. An IT placed 0.33 oct above f(2) removed most of this banding, revealing DPOAE components originating basal to the IT frequency place. These findings suggest that the commonly accepted two-source model of DPOAE generation may need to be qualified when higher primary-tone levels are utilized.

Noise-induced hearing loss in mice treated with antiretroviral drugs.

The results reported here for CBA/CaJ mice describe the effects of regular dosing with a common antiretroviral drug combination on outer hair cell (OHC) function using measures of 2f1-f2 distortion product otoacoustic emissions (DPOAEs) and auditory brainstem responses (ABRs). Specifically, experimental mice were treated daily over a 3-mo period with the nucleoside reverse transcriptase inhibitors (NRTIs), zidovudine (ZDV) and lamivudine (3TC), dissolved in their drinking water, while their control counterparts received untreated water. DPOAE levels and ABR detection thresholds prior to and after 12 wk of NRTI treatment did not differ between experimental and control groups. To assess whether NRTI treatment potentiates the adverse effects of noise over-exposure on OHC function, both experimental and control mice were exposed 1 wk later, while still on the drug regimen, to a 10-kHz octave-band noise (OBN) at 105-dB SPL for 1h. A major outcome of the sound over-exposure episode was that the NRTI-pretreated mice showed significantly greater permanent OBN-induced reductions in DPOAE levels at 2 wk postexposure than were observed for the untreated control animals. These findings support the notion that a synergistic relationship exists between certain NRTIs and intense sounds in that such preexposure drug treatments produced greater noise-induced decreases in DPOAE activity than did noise exposure alone. This drug/noise interaction is consistent with the known harmful effects of NRTIs on cellular mitochondrial activity.

Comparison of distortion product otoacoustic emissions in 28 inbred strains of mice.

Cochlear function was evaluated in a longitudinal study of 28 inbred strains of mice at 3 and 5 mo of age using measures of distortion product otoacoustic emissions (DPOAEs) in response to a federal initiative to develop rapid mouse phenotyping methodologies. DP-grams at f(2) frequencies ranging from 6.3 to 54.2kHz were obtained in about 3min/ear by eliciting 2f(1)-f(2) DPOAEs in 0.1-octave steps of f(2) with primary tones at L(1)=L(2) =55, 65, and 75dB SPL. CBA/CaJ mice exhibited average levels of approximately 26dB SPL and this strain was selected as the normal reference strain against which the others were compared. Based upon the configurations of their DP-grams, the 28 mouse strains could be categorized into four distinct groups. That is, nine of the strains including the CBA were designated as the CBA-like group because these mice displayed robust DPOAE levels across frequency. In contrast, the remaining three groups all exhibited irregular DP-gram patterns. Specifically, eight of the remaining 19 strains showed a progressive high- to low-frequency reduction in DPOAE levels that was typical of age-related hearing loss (AHL) associated with mouse strains homozygous for the ahl allele and were labeled as AHL-like strains. Seven strains demonstrating relatively even patterns of reduced DPOAE levels across the frequency-test range were designated as Flat-loss strains. Finally, the remaining four strains exhibited no measurable DPOAEs at either 3 or 5 mo of age and thus were classified as Absent strains. Extending the f(2) test frequencies up to approximately 54kHz led to the detection of very early-onset reductions in cochlear function in non-CBA-like groups so that all strains could be categorized by 3 mo of age. Predictably, the AHL-like strains showed more pronounced DPOAE losses at 5 mo than at 3 mo. A similar deterioration in DPOAE levels was not apparent for the Flat-loss strains. Both the AHL-like and Flat-loss strains showed considerably more variability in DPOAE levels than did the CBA-like strains. Together, these findings indicate that DP-grams adequately reveal both frequency-specific loss patterns and details of inbred strain variability.

Comparing Distortion Product Otoacoustic Emissions to Intracochlear Distortion Products Inferred from a Noninvasive Assay.

The behavior of intracochlear distortion products (iDPs) was inferred by interacting a probe tone (f3) with the iDP of interest to produce a "secondary" distortion product otoacoustic emission termed DPOAE(2ry). Measures of the DPOAE(2ry) were then used to deduce the properties of the iDP. This approach was used in alert rabbits and anesthetized gerbils to compare ear-canal 2f1-f2 and 2f2-f1 DPOAE f2/f1 ratio functions, level/phase (L/P) maps, and interference-response areas (IRAs) to their simultaneously collected DPOAE(2ry) counterparts. These same measures were also collected in a human volunteer to demonstrate similarities with their laboratory animal counterparts and their potential applicability to humans. Results showed that DPOAEs and inferred iDPs evidenced distinct behaviors and properties. That is, DPOAE ratio functions elicited by low-level primaries peaked around an f2/f1 = 1.21 or 1.25, depending on species, while the corresponding inferred iDP ratio functions peaked at f2/f1 ratios of ~1. Additionally, L/P maps showed rapid phase variation with DPOAE frequency (fdp) for the narrow-ratio 2f1-f2 and all 2f2-f1 DPOAEs, while the corresponding DPOAE(2ry) measures evidenced relatively constant phases. Common features of narrow-ratio DPOAE IRAs, such as large enhancements for interference tones (ITs) presented above f2, were not present in DPOAE(2ry) IRAs. Finally, based on prior experiments in gerbils, the behavior of the iDP directly measured in intracochlear pressure was compared to the iDP inferred from the DPOAE(2ry) and found to be similar. Together, these findings are consistent with the notion that under certain conditions, ear-canal DPOAEs provide poor representations of iDPs and thus support a "beamforming" hypothesis. According to this concept, distributed emission components directed toward the ear canal from the f2 and basal to f2 regions can be of differing phases and thus cancel, while these same components directed toward fdp add in phase.

Human efferent adaptation of DPOAEs in the L1,L2 space.

The adaptive properties of distortion product otoacoustic emissions (DPOAEs) at 2f(1)-f2 were investigated in 12 ears of normally hearing adults aged 18-30 years using long-lasting 1-s primary-tone on-times. In this manner, DPOAE adaptation at a single f2 of 1.55 kHz (f2/f1=1.21) was evaluated as a function of the levels of the primary tones in a matrix of L1, L2 settings, which varied from 45 to 80 dB SPL, in 5-dB steps. DPOAEs were elicited under both monaural and binaural stimulus-presentation conditions. Adaptation was defined as the difference in DPOAE levels between the initial 92-ms baseline measure using a standard protocol and one obtained during the final 92 ms of the prolonged 1-s primary-tones. These differences were averaged across subjects to create contour plots of mean adaptation in the L1,L2 space. The 2f(1)-f2 DPOAE revealed consistent regions of suppression (-0.5 dB difference) or enhancement (+0.5 dB difference) with respect to baseline measures within the L(1),L(2) matrix for both acoustic-stimulation conditions. Specifically, 2f(1)-f2 DPOAE suppressions of 1-2 dB occurred for both monaural and binaural presentations, typically at level combinations in which L1>L2. In contrast, larger 2f(1)-f2 DPOAE enhancements of 3-4 dB occurred for only the binaural condition, at primary-tone level combinations where L1

Efficacy and safety of N-acetylcysteine in prevention of noise induced hearing loss: a randomized clinical trial.

Despite a robust hearing conservation program, military personnel continue to be at high risk for noise induced hearing loss (NIHL). For more than a decade, a number of laboratories have investigated the use of antioxidants as a safe and effective adjunct to hearing conservation programs. Of the antioxidants that have been investigated, N-acetylcysteine (NAC) has consistently reduced permanent NIHL in the laboratory, but its clinical efficacy is still controversial. This study provides a prospective, randomized, double-blinded, placebo-controlled clinical trial investigating the safety profile and the efficacy of NAC to prevent hearing loss in a military population after weapons training. Of the 566 total study subjects, 277 received NAC while 289 were given placebo. The null hypothesis for the rate of STS was not rejected based on the measured results. While no significant differences were found for the primary outcome, rate of threshold shifts, the right ear threshold shift rate difference did approach significance (p = 0.0562). No significant difference was found in the second primary outcome, percentage of subjects experiencing an adverse event between placebo and NAC groups (26.7% and 27.4%, respectively, p = 0.4465). Results for the secondary outcome, STS rate in the trigger hand ear, did show a significant difference (34.98% for placebo-treated, 27.14% for NAC-treated, p-value = 0.0288). Additionally, post-hoc analysis showed significant differences in threshold shift rates when handedness was taken into account. While the secondary outcomes and post-hoc analysis suggest that NAC treatment is superior to the placebo, the present study design failed to confirm this. The lack of significant differences in overall hearing loss between the treatment and placebo groups may be due to a number of factors, including suboptimal dosing, premature post-exposure audiograms, or differences in risk between ears or subjects. Based on secondary outcomes and post hoc analyses however, further studies seem warranted and are needed to clarify dose response and the factors that may have played a role in the observed results.

Suppression and enhancement of distortion-product otoacoustic emissions by interference tones above f(2). II. Findings in humans.

Distortion-product otoacoustic emission (DPOAE) suppression tuning curves (STCs) can be obtained in a variety of laboratory animals and humans by sweeping the frequencies and levels of a third tone (f(3)) around a set of f(1) and f(2) primaries. In small laboratory animals, it was previously observed that, when the suppressor tone (f(3)) is above f(2), substantial suppression and or enhancement (suppression/enhancement) could be obtained. In the present study, it was of interest to determine if similar suppression/enhancement phenomena could be observed in humans and to what extent this might influence the interpretation of STC results reported in the literature. To this end, STCs were measured for DPOAEs at 2f(1)-f(2) and 2f(2)-f(1) in human subjects at geometric-mean frequencies (GM) of 1, 2, 3, and 4 kHz, and primary-tone equilevels of 80/80 and 75/75 dB SPL and unequal levels of 65/55 dB SPL. Overall, STC parameters were found to be comparable to those reported in the literature. For the 2f(1)-f(2) DPOAE, STC tip frequencies tuned to the region of the primaries, and tip frequencies were slightly influenced by primary-tone level. STC tip thresholds were typically within 10 dB of the level of L(2), and Q(10dB) values ranged from 1.0 to 2.5, which was consistent with the higher-level primaries employed. The 2f(1)-f(2) DPOAE showed consistent regions of suppression that were approximately an octave above the GM for the 1-kHz, 65/55-dB SPL condition. The 2f(2)-f(1) DPOAE tuned to its characteristic place above f(2) and showed reliable enhancement above the STC tip region for the 1-kHz, 75/75-dB SPL primaries. Overall, the results clearly revealed that human ears also display suppression/enhancement phenomena when f(3) reaches frequencies considerably above f(2). If suppression/enhancement phenomena reflect secondary DPOAE sources, then these sources are present in the ear-canal signal from humans as well as small laboratory animals.

Evaluating cochlear function and the effects of noise exposure in the B6.CAST+Ahl mouse with distortion product otoacoustic emissions.

Cochlear function and susceptibility to noise over-exposure were examined in the congenic mouse strain B6.CAST+Ahl (B6.CAST) and compared to these same features in the CAST/Ei (CAST) and C57BL/6J (C57) parental strains. For both types of comparisons, the primary measure was the distortion-product otoacoustic emissions (DPOAE) at 2f1-2f2. Our assumption was that the B6.CAST mouse was corrected for the early onset age-related hearing loss (AHL) exhibited by one of its parental strains (C57) by the age-resistant properties of its other parental strain (CAST), and thus would exhibit neither AHL nor susceptibility to noise overstimulation effects. With respect to cochlear function, for 2.5-month mice, there was a tendency for DPOAEs to be slightly lower for mid-frequency primary tones for both C57 and B6.CAST mice, while the former mice showed clear AHL effects at the highest test frequency. However, by 5 months of age, the B6.CAST mice, like the CAST mice, displayed robust DPOAE levels that were significantly larger than DPOAE levels for the C57 mice, which were essentially absent for frequencies above about 30 kHz. To investigate the role of the Ahl gene in the susceptibility of the cochlea to the effects of noise over-exposure, two distinct paradigms consisting of temporary (TTS: 1-min, 105-dB SPL, 10-kHz pure tone) and permanent (PTS: 1-h, 105-dB SPL, 10-kHz octave band noise) threshold-shift protocols were used. The brief TTS exposure produced reversible reductions in DPOAEs that for both the B6.CAST and CAST mice recovered to within a few dB of their baseline levels by 3 min post-exposure. In contrast, the C57 mice recovered somewhat slower and, by 5 min post-exposure, emission levels were still 5 dB or more below their corresponding pre-exposure values. At 3 months of age, the TTS mice along with another group of naïve subjects representing the same three mouse strains were exposed to the PTS paradigm. By 4 days post-exposure, for B6.CAST and CAST mice, DPOAE levels had recovered to their pre-exposure control levels. However, DPOAEs for the C57 mice at most of the measurable frequencies were at least 10-30 dB lower than their counterpart baseline levels. Together these data suggest that the Ahl allele in the C57 strain contributes to both the early onset AHL exhibited by these mice as well as their susceptibility to both TTS and PTS over-exposures.

Distortion product otoacoustic emissions show exceptional resistance to noise exposure in MOLF/Ei mice.

Baseline distortion-product otoacoustic emissions (DPOAEs) at several primary-tone levels were compared between naive 2- to 3-month old inbred CBA/CaJ (CBA) and wild-derived MOLF/Ei (MOLF) mice. Only minor DPOAE differences were noted between the two strains and these differences were not systematic across frequency or test levels. These emission findings were consistent with earlier results on auditory brainstem response thresholds reported by others [Zheng et al., Hear. Res. 130 (1999) 94-107] thus suggesting that both CBA and MOLF strains have normal hearing. Subsequent episodes of over-exposure to a 105-dB SPL, octave-band noise centered at 10 kHz for 8 h revealed that MOLF DPOAEs were exceptionally resistant to the adverse aftereffects of excessive noise exposure as compared to CBA mice. Unlike the noise-exposure resistant inbred 129/SvEvTac strain, which has reduced baseline DPOAE levels especially at high frequencies, MOLF mice have normal DPOAEs making the interpretation of noise-exposure effects more straightforward.

Eph receptor deficiencies lead to altered cochlear function.

Ephrins and Eph receptors are a family of molecules that have been implicated in many developmental processes including neuronal network formation, guidance of cell migration, and axonal pathfinding. These molecules exhibit the ability to send bidirectional signals following ligand-receptor interactions resulting from cell-cell contacts. Gene-targeted knockout mice of B-class ephrins and Eph receptors have been shown to display phenotypic responses that correlate with anatomical defects. For example, disruption of the EphB2 receptor leads to defects of the vestibular system, including pathfinding abnormalities in efferent axons and reduced endolymph production. Such developmental distortions lead to deficiencies in ionic homeostasis and repetitive circling behaviors. The present study demonstrates that B-class ephrins and Eph receptors are expressed in cochlear tissues, suggesting that they may play some role in auditory function. To determine whether ephrins and Eph receptors have a functional role in the peripheral auditory system, distortion-product otoacoustic emission (DPOAE) levels, collected across a broad frequency range, were compared between groups of mice expressing different Eph receptor genotypes. In particular, EphB1 and EphB3 receptor knockout mice exhibited significantly diminished DPOAE levels as compared to wild-type littermates, indicating that these specific Eph receptors are necessary for normal cochlear function.

Otoacoustic emissions.

PURPOSE OF REVIEW: Otoacoustic emissions offer the practitioner a number of beneficial features as a noninvasive and objective measure of the ear's ability to process acoustic stimuli. RECENT FINDINGS: Since their discovery, a number of clinical applications of otoacoustic emissions have been established, including their utility in the differential diagnosis of sensorineural hearing loss, in the screening of cochlear function in infants and other difficult-to-test patients, and in the monitoring of outer hair cell healthiness in patients who are exposed to potentially damaging agents or who have progressive hearing ailments. SUMMARY: Clinical applications of OAEs have developed very rapidly and OAEs have become the standard of care, at least, for pediatric patients.

Preventing internal auditory artery vasospasm using topical papaverine: an animal study.

BACKGROUND: Internal auditory artery (IAA) spasm is thought to be one of the causes of postoperative sensory hearing loss after attempted hearing preservation removal of an acoustic neuroma. The use of topical papaverine, a nonspecific vasodilator, to prevent vascular insufficiency to the inner ear and to improve hearing outcomes has been suggested but not proven. MATERIALS AND METHODS: Vasospasm was mechanically induced by compressing the IAA in the control ears of six rabbits after application of topical saline. The subsequent reduction of cochlear blood flow (CBF) was measured using a laser-Doppler (LD) flow-monitoring technique. Functional loss of cochlear activity was verified with distortion product otoacoustic emissions (DPOAE). The contralateral experimental ears were treated with the topical application of papaverine directly to the IAA and cochleovestibular nerve complex. CBF and DPOAE were compared between the control and papaverine treated ears for 3-minute and 5-minute IAA compressions. RESULTS: Every control ear demonstrated some degree of postcompression IAA vasospasm (i.e., reduced CBF) and reduction of DPOAE. Nearly complete recovery of CBF and DPOAE to baseline was observed in all of the papaverine treated ears. CONCLUSIONS: An animal model of IAA vasospasm was described. Mechanically induced vasospasm of the IAA was prevented by the topical application of papaverine. These findings have clinical implications for surgical procedures involving the internal auditory canal/cerebellopontine angle such as acoustic neuroma removal.

Noise-induced changes in gene expression in the cochleae of mice differing in their susceptibility to noise damage.

The molecular mechanisms underlying the vast differences between individuals in their susceptibility to noise-induced hearing loss (NIHL) are unknown. The present study demonstrated that the effects of noise over-exposure on the expression of molecules likely to be important in the development of NIHL differ among inbred mouse strains having distinct susceptibilities to NIHL including B6 (B6.CAST) and 129 (129X1/SvJ and 129S1/SvImJ) mice. The noise-exposure protocol produced a loss of 40 dB in hearing sensitivity in susceptible B6 mice, but no loss for the two resistant 129 substrains. Analysis of gene expression in the membranous labyrinth 6 h following noise exposure revealed upregulation of transcription factors in both the susceptible and resistant strains. However, a significant induction of genes involved in cell-survival pathways such as the heat shock proteins HSP70 and HSP40, growth arrest and DNA-damage-inducible protein 45ß (GADD45ß), and CDK-interacting protein 1 (p21(Cip1)) was detected only in the resistant mice. Moreover, in 129 mice significant upregulation of HSP70, GADD45ß, and p21(Cip1) was confirmed at the protein level. Since the functions of these proteins include roles in potent anti-apoptotic cellular pathways, their upregulation may contribute to protection from NIHL in the resistant 129 mice.