Background: The ability of drugs to reduce noise induced hearing loss (NIHL) has been evaluated in diverse experimental conditions (animal species, noise intensities, durations, assessment techniques, etc), making it difficult to assess their relative efficacy. The present study was designed to provide more uniform comparisons and to allow to a better understanding of the mechanism of the NIHL. Methods: The drugs studied included furosemide (loop diuretic) and the antioxidants N Acetyl-L-Cysteine, vitamins A, C, E with the vasodilator magnesium. Mice were exposed to a continuous broadband noise (113 dB SPL for 3.5 hours) and the NIHL was assessed in all animals before noise exposure and 1 week after with auditory nerve brainstem evoked responses (ABR) to broadband clicks and to 8 kHz tone bursts. Results: Each of the drugs alone and in combination led to similar reductions in NIHL. Conclusions: The loop diuretic furosemide, by reducing the magnitude of the endocochlear potential in scala media, probably depressed active vibrations of the outer hair cells and basilar membrane, resulting in reduction of free radical formation during the noise exposure. The antioxidants N Acetyl-L-Cysteine and vitamins A, C, E with the vasodilator magnesium presumably counteract the free radicals. Thus, the administration of the antioxidants to animals in which free radical formation had already been reduced by previous injection of furosemide did not have an additional protective effect on the NIHL.

Background: A major cause of the hearing loss following exposure to intense noise involves release of free radicals resulting from the elevated metabolism. The free radicals induce damage to several of the components of the cochlear amplifier including the outer hair cells and indirectly to the transduction currents. Salicylic acid induces a reversible hearing loss since it binds to the motor protein prestin in the outer hair cells, reducing electromotility. Furosemide also induces a reversible hearing loss since it reduces the endocochlear potential which is a major component of the cochlear transduction currents. On the other hand, each of these drugs also provides protection from a noise induced hearing loss if they are injected just before a noise exposure, probably as a result of the decreased metabolism induced in their presence, with release of lower levels of free radicals. In this study, both drugs were administered in order to assess whether their protective effects would be additive. Methods: The study was conducted on normal hearing albino mice of the Sabra strain. They were injected with either salicylic acid alone (N = 11), or furosemide alone (N = 14), or both together (N = 14), or with saline control (N = 11) and exposed to broad band noise for 3.5 hours. An additional group of 9 mice was injected with both salicylic acid and furosemide, but not exposed to noise. The degree of the resulting hearing loss was assessed by recording thresholds of the auditory nerve brainstem evoked responses to broad band clicks before the injections and noise, and 7, 14 and 21 days after. Results: The noise induced hearing loss in the mice injected with salicylic acid alone or furosemide alone was smaller than in those injected with saline, i.e. these drugs provided protection, as in previous studies in this laboratory. There was no threshold elevation after two weeks in the mice injected with both drugs without noise exposure, i.e. the effects of the two drugs given together was reversible. On the other hand, there was a significant hearing loss (i.e. threshold elevation) in the group which received both drugs and was also exposed to noise, with mean threshold elevations of 38.8 ± 19.0 dB and 28.3 ± 11.7 dB 7 days after noise exposure. Conclusions: This result is very surprising, if not paradoxical. Drugs which provide protection from a noise induced hearing loss when administered alone, not only do not provide protection when given together, but also induce a greater hearing loss when accompanied by noise. This observation may be related to the finding that the depression of the endocochlear potential normally caused by furosemide is reduced in the presence of salicylic acid, so that the protection usually provided by furosemide is not present when it is administered together with salicylic acid. Thus it seems that each drug may interfere with the protective action of the other when coupled with noise.

Background: The permanent hearing loss following exposure to intense noise can be due either to mechanical structural damage (tearing) caused directly by the noise or to metabolic (biochemical) damage resulting from the elevated levels of free radicals released during transduction of the sound overstimulation. Drugs which depress active cochlear mechanics (e.g. furosemide and salicylic acid) or anti-oxidants (which counteract the free radicals) are effective in reducing the threshold shift (TS) following broadband continuous noise. This study was designed to determine whether furosemide can reduce the TS following exposure to impulse noise, similar to its action with continuous broadband noise. Methods: Shortly after furosemide injection, mice were exposed to simulated M16 rifle impulse noise produced by different loudspeakers and amplifiers in different exposure settings and, in other experiments, also to actual M16 rifle shots. Results: Depending on the paradigm, the simulated noises either did not produce a TS, or the TS was reduced by furosemide. The drug was not effective in reducing TS resulting from actual impulse noise. Conclusion: Simulated M16 rifle impulse noise may not truly replicate the rapid rise time and very high intensity of actual rifle shots so that the TS following exposure to such noise can be reduced by these drugs. On the other hand, actual M16 impulse noise probably causes direct (frank) mechanical damage, which is not reduced by these drugs.

Conclusion Cochlea can be directly excited by fluid (soft-tissue) stimulation. Objective To determine whether there is no difference in auditory-nerve-brainstem evoked response (ABR) thresholds to fluid stimulation between normal and animal models of post radical-mastoidectomy, as seen in a previous human study. Background It has been shown in humans that hearing can be elicited with stimulation to fluid in the external auditory meatus (EAM), and radical-mastoidectomy cavity. These groups differed in age, initial hearing, and drilling exposure. To overcome this difference, experiments were conducted in sand-rats, first intact, and after inducing a radical-mastoidectomy. Methods The EAM of five sand-rats was filled with 0.3 ml saline. ABR thresholds were determined in response to vibratory stimulation by a clinical bone-vibrator with a plastic rod, applied to the saline in the EAM. Then the tympanic membrane was removed, and malleus dislocated (radical-mastoidectomy model). The cavity was filled with 0.45 ml saline and the ABR threshold was determined in response to vibratory stimulation to the cavity fluid. Results There was no difference in ABR fluid thresholds to EAM and mastoidectomy cavity stimulation. Air-conduction stimulation from the bone-vibrator was not involved (conductive loss due to fluid). Bone-conduction stimulation was not involved (large difference in acoustic impedance between fluid and bone).

OBJECTIVES: To assess bone conduction (BC) thresholds following radical mastoidectomy and subtotal petrosectomy, in which the tympanic membrane and the ossicular chain, responsible for osseous BC mechanisms, are surgically removed. The removal of the tympanic membrane and the ossicular chain would reduce the contributions to BC threshold of the following four osseous BC mechanisms: the occlusion effect of the external ear, middle ear ossicular chain inertia, inner ear fluid inertia, and distortion (compression–expansion) of the walls of the inner ear. MATERIALS and METHODS: BC thresholds were determined in 64 patients who underwent radical mastoidectomy and in 248 patients who underwent subtotal petrosectomy. RESULTS: BC thresholds were normal (≤15 dB HL, i.e., better) in 19 (30%) radical mastoidectomy patients and in 19 (8%) subtotal petrosectomy patients at each of the frequencies assessed (0.5, 1.0, 2.0, and 4.0 kHz). CONCLUSION: Normal BC thresholds seen in many patients following mastoidectomy and petrosectomy may be induced by a non-osseous mechanism, and the onset (“threshold”) of the classical osseous BC mechanisms may be somewhat higher. Cite this article as: Kaufmann Yehezkely M, Grinblat G, Geal Dor M, Chordekar S, Perez R, Adelman C, et al. Implications for Bone Conduction Mechanisms from Thresholds of Post Radical Mastoidectomy and Subtotal Petrosectomy Patients. J Int Adv Otol 2019; 15(1): 8-11.