Mid-term evaluation of perioperative i.v. corticosteroid treatment efficacy on overall and audiological outcome following CO2 laser stapedotomy: a retrospective study of 84 cases.

PURPOSE: Our aim was to determine whether perioperatively administered corticosteroid treatment has any beneficial effect on the outcome of stapes surgery, with special regard to the audiological results and early postoperative morbidity. METHODS: 84 CO2 laser stapedotomies performed in our institute between 2013 and 2018 were included in our investigation. All cases underwent preoperative and mid-term postoperative pure-tone audiometric evaluation. Vestibular complications were also evaluated. The cases were subdivided into two groups, 23 patients received perioperative i.v. methylprednisolone treatment ("S") while the other 61 patients ("nS") did not receive any adjuvant pharmacological therapy. The data were analyzed retrospectively using IBM SPSS Statistics. RESULTS: CO2 laser stapedotomy proved to be a successful intervention with a significant improvement in ABG and AC thresholds as well. Long-term BC levels were significantly better compared to preoperative ones in the S group; however, in the nS group, no difference could be shown. Hearing and ABG gain were significantly superior in group S [28.1 dB (SD11.2) vs. 18.1 dB (SD 10.9) and 23.9 dB(SD 9.8) vs. 17.2 dB (SD 9.5), respectively]. CONCLUSION: No significant inner ear damage was detectable in the results of our CO2 laser stapedotomy method; however, the positive effect of corticosteroid treatment could be demonstrated through the postoperative hearing levels. We found no statistical difference in early postoperative morbidity. According to our data, the routine administration of corticosteroids during stapes surgery could be an issue worthy of consideration. The effects of perioperative treatment vs that on the first day after surgery, and topical vs. systemic treatment could be the subject of further investigation in a prospective manner.

Neurochemical evidence of dopamine release by lateral olivocochlear efferents and its presynaptic modulation in guinea-pig cochlea.

In this study, using an in vitro superfusion technique for the first time, we provide direct neurochemical evidence of the transmitter role of dopamine at the level of lateral olivocochlear efferent fibres of the guinea-pig cochlea. Our results revealed that nerve terminals are able to take up and release dopamine upon axonal stimulation. Since dopamine is thought to protect the afferent nerve fibres from damage due to acoustic trauma or ischaemia, enhancement of the release of dopamine, a potential therapeutic site of these injuries, was investigated. Positive modulation of dopamine release has been shown by a D1 dopamine receptor agonist, an antagonist and piribedil. Furthermore, negative feedback on the stimulation-evoked release of dopamine via D2 dopamine receptors has been excluded. Electrical stimulation of the cochlear tissue produced a significant and reproducible release of [3H]dopamine, which could be blocked by tetrodotoxin (1 microM) and cadmium (100 microM), proving that axonal activity releases dopamine and its dependence on Ca2+ influx verifies its neuronal origin. Nomifensine, a high-affinity dopamine uptake blocker, prevented the tissue from taking up [3H]dopamine from the bathing solution, also indicating the neural origin of dopamine released in response to stimulation. SKF-38393 (a selective D1 agonist) increased both the resting and electrically evoked release of dopamine. Piribedil (a D3/D2/D1 agonist), a drug under investigation, known to prevent acoustic trauma or ischaemia-induced hearing loss, had a similar and concentration-dependent increasing effect on both resting and evoked release of dopamine. The effect of both drugs on stimulation-evoked release could be prevented by SKF-83566 (a selective D1 antagonist). However, SKF-83566 alone enhanced the resting and axonal conduction-associated release of dopamine. D2 agonists and antagonists failed to modulate the release of dopamine, indicating the lack of negative feedback modulation of dopamine release. Our results suggest that the release of dopamine was subjected to modulation by a D1 receptor agonist and an antagonist. In addition, it is concluded that D2 receptors are not involved in the modulation of dopamine release. This observation may have clinical relevance in the prevention or therapy of particular types of hearing loss, because enhanced dopaminergic input into the primary auditory neuron may inhibit the (over)excitation of this neuron by glutamatergic input from inner hair cells.

A new aspect of aminoglycoside ototoxicity: impairment of cochlear dopamine release.

Aminoglycoside ototoxicity is a well-documented process via several pathophysiological pathways. The protective role of cochlear dopamine, released from the lateral olivocochlear efferents, was implicated previously in case of ischemia or acoustic trauma, as it postsynaptically inhibits the effect of excessively released glutamate from the hair cells. In our in vitro superfusion experiments we showed that neomycin dose- dependently inhibits the dopamine release from isolated guinea pig cochlea, while gentamicin and kanamycin was ineffective on it. After chronic application of neomycin the dopamine outflow did not change significantly, suggesting an adaptive process. In our experiments we have found a possibly new action site of one of the aminoglycoside antibiotics, neomycin.

Characterization of voltage dependent calcium channels on the lateral olivocochlear efferent fibers of the guinea pig.

Using in vitro superfusion technique the release of [3H]-dopamine from the lateral olivocochlear efferent fibers of the cochlea was investigated. Our previous study gave the first neurochemical evidence for the transmitter role of dopamine and proved its neuronal origin. Using specific antagonists now we characterized the voltage-dependent calcium channels (VDCCs) involved in the release of dopamine evoked by electrical stimulation of the cochlear tissue. Verapamil or nifedipine, and Ni2+ failed to affect the release, indicating that neither L-, nor T-type VDCCs are essential for the release process. The fact that omega-conotoxin inhibited the release of dopamine from lateral olivocochlear efferent fibers suggests, that N-type VDCCs are required for the calcium influx during electrical stimulation. These VDCCs could be presynaptic targets of modulation of the dopamine release under pathological conditions or in therapy.

Veratridine-evoked release of dopamine from guinea pig isolated cochlea.

Dopamine released from the lateral olivocochlear efferent system is thought to inhibit the toxic effect of the extreme glutamate outflow from the inner hair cells during ischemia or acoustic trauma. Using in vitro microvolume superfusion, we have studied the release of [(3)H]dopamine from the lateral olivocochlear efferent bundle of guinea pig in response to accumulation of [Na(+)](i), under condition characteristics of ischemia. Veratridine, that acts only on excitable membranes as a specific activator of voltage-sensitive sodium channels, significantly increased the electrically evoked release of [(3)H]dopamine, which was completely inhibited by tetrodotoxin. Dizocilpine (MK-801), a non-competitive NMDA-receptor antagonist, and GYKI-52466, a selective non-NMDA-receptor antagonist, had no effect on veratridine-induced [(3)H]dopamine release. Our data provide further evidence that the cochlear release of dopamine is of neural origin and possibly independent on a local effect of glutamate. The veratridine-induced transmitter release in the cochlea will be a very useful method in studying the effect of drugs on ischemic injury.