Decrease In Cochlear Blood Flow Research Articles

Cochlear implantation impairs intracochlear microcirculation and counteracts iNOS induction in guinea pigs.

Preservation of residual hearing remains a great challenge during cochlear implantation. Cochlear implant (CI) electrode array insertion induces changes in the microvasculature as well as nitric oxide (NO)-dependent vessel dysfunction which have been identified as possible mediators of residual hearing loss after cochlear implantation. A total of 24 guinea pigs were randomized to receive either a CI (n = 12) or a sham procedure (sham) by performing a cochleostomy without electrode array insertion (n = 12). The hearing threshold was determined using frequency-specific compound action potentials. To gain visual access to the stria vascularis, a microscopic window was created in the osseous cochlear lateral wall. Cochlear blood flow (CBF) and cochlear microvascular permeability (CMP) were evaluated immediately after treatment, as well as after 1 and 2 h, respectively. Finally, cochleae were resected for subsequent immunohistochemical analysis of the iNOS expression. The sham control group showed no change in mean CBF after 1 h (104.2 ± 0.7%) and 2 h (100.8 ± 3.6%) compared to baseline. In contrast, cochlear implantation resulted in a significant continuous decrease in CBF after 1 h (78.8 ± 8.1%, p < 0.001) and 2 h (60.6 ± 11.3%, p < 0.001). Additionally, the CI group exhibited a significantly increased CMP (+44.9% compared to baseline, p < 0.0001) and a significant increase in median hearing threshold (20.4 vs. 2.5 dB SPL, p = 0.0009) compared to sham after 2 h. Intriguingly, the CI group showed significantly lower iNOS-expression levels in the organ of Corti (329.5 vs. 54.33 AU, p = 0.0003), stria vascularis (596.7 vs. 48.51 AU, p < 0.0001), interdental cells (564.0 vs. 109.1 AU, p = 0.0003) and limbus fibrocytes (119.4 vs. 18.69 AU, p = 0.0286). Mechanical and NO-dependent microvascular dysfunction seem to play a pivotal role in residual hearing loss after CI electrode array insertion. This may be facilitated by the implantation associated decrease in iNOS expression. Therefore, stabilization of cochlear microcirculation could be a therapeutic strategy to preserve residual hearing.

The mechanoelectrical transducer channel is not required for regulation of cochlear blood flow during loud sound exposure in mice

The mammalian cochlea possesses unique acoustic sensitivity due to a mechanoelectrical ‘amplifier’, which requires the metabolic support of the cochlear lateral wall. Loud sound exposure sufficient to induce permanent hearing damage causes cochlear blood flow reduction, which may contribute to hearing loss. However, sensory epithelium involvement in the cochlear blood flow regulation pathway is not fully described. We hypothesize that genetic manipulation of the mechanoelectrical transducer complex will abolish sound induced cochlear blood flow regulation. We used salsa mice, a Chd23 mutant with no mechanoelectrical transduction, and deafness before p56. Using optical coherence tomography angiography, we measured the cochlear blood flow of salsa and wild-type mice in response to loud sound (120 dB SPL, 30 minutes low-pass filtered noise). An expected sound induced decrease in cochlear blood flow occurred in CBA/CaJ mice, but surprisingly the same sound protocol induced cochlear blood flow increases in salsa mice. Blood flow did not change in the contralateral ear. Disruption of the sympathetic nervous system partially abolished the observed wild-type blood flow decrease but not the salsa increase. Therefore sympathetic activation contributes to sound induced reduction of cochlear blood flow. Additionally a local, non-sensory pathway, potentially therapeutically targetable, must exist for cochlear blood flow regulation.

Mitochondrial Damage and Necroptosis in Aging Cochlea.

Age-related hearing loss (ARHL) is an irreversible, progressive neurodegenerative disorder and is presently untreatable. Previous studies using animal models have suggested mitochondrial damage and programmed cell death to be involved with ARHL. Thus, we further investigated the pathophysiologic role of mitochondria and necroptosis in aged C57BL/6J male mice. Aged mice (20 months old) exhibited a significant loss of hearing, number of hair cells, neuronal fibers, and synaptic ribbons compared to young mice. Ultrastructural analysis of aged cochleae revealed damaged mitochondria with absent or disorganized cristae. Aged mice also showed significant decrease in cochlear blood flow, and exhibited increase in gene expression of proinflammatory cytokines (IL-1β, IL-6, and TNF-α), receptor-interacting serine/threonine-protein kinase 1 and 3 (RIPK1 and RIPK3) and the pseudokinase mixed-lineage kinase domain-like (MLKL). Immunofluorescence (IF) assays of cytochrome C oxidase I (COX1) confirmed mitochondrial dysfunction in aged cochleae, which correlated with the degree of mitochondrial morphological damage. IF assays also revealed localization and increased expression of RIPK3 in sensorineural tissues that underwent significant necroptosis (inner and outer hair cells and stria vascularis). Together, our data shows that the aging cochlea exhibits damaged mitochondria, enhanced synthesis of proinflammatory cytokines, and provides new evidence of necroptosis in the aging cochlea in in vivo.

Resistance of Gerbil Auditory Function to Reversible Decrease in Cochlear Blood Flow

The objective was to design in gerbils a model of reversible decrease in cochlear blood flow (CBF) and analyze its influence on cochlear function. In Mongolian gerbils injected with ferromagnetic microbeads, a magnet placed near the porus acusticus allowed CBF to be manipulated. The cochlear microphonic potential (CM) from the basal cochlea was monitored by a round-window electrode. In 13 of the 20 successfully injected gerbils, stable CBF reduction was obtained for 11.5 min on average. The CM was affected only when CBF fell to less than 60% of its baseline, yet remained >40% of its initial level in about 2/3 of such cases. After CBF restoration, CM recovery was fast and usually complete. Reduced CM came with a 35- to 45-dB threshold elevation of neural responses determined by compound action potentials. This method allowing reversible changes of CBF confirms the robustness of cochlear function to decreased CBF. It can be used to study whether a hypovascularized cochlea is abnormally sensitive to stress.

The effect of propofol infusion with topical epinephrine on cochlear blood flow and hearing: An experimental study

Propofol is the most commonly used intravenous (IV) anesthetic agent and is associated with hypotension upon induction of anesthesia. Intravenous propofol infusion has several properties that may be beneficial to patients undergoing middle ear surgery. Topical application of concentrated epinephrine is a valuable tool for achieving hemostasis in the middle ear and during mastoid surgery. The purpose of the present study was to determine the effects of propofol infusion with topical epinephrine on cochlear blood flow (CBF) and hearing in rats. Twenty one male Sprague-Dawley rats were divided into three groups. The rate of intravenous infusion of propofol was 4-6ml/kg/hour. The first group (control group, n=7) was given IV infusion of phosphate buffered saline (PBS) with topical application of PBS in the round window. In study group A (n=7), the effect of topical phosphate buffered saline with IV infusion of propofol on CBF and hearing was evaluated. In study group B (n=7), additional effects of topical epinephrine with IV infusion of propofol on CBF and hearing were evaluated. The laser Doppler blood flowmeter, CBF, and the mean arterial blood pressure (MAP) were measured and analyzed. Additionally, hearing test using auditory brainstem response (ABR) was performed in both groups. In both groups, infusion of propofol induced a time-dependent decrease in MAP. Approximately 30min after the start of the propofol infusion, the CBF started to decrease slowly. The decrease in CBF was significantly greater in the study group compared to the control group. The threshold was elevated in the study group relative to the control group. During middle ear surgery, use of IV infusion of propofol with topical epinephrine cotton ball or cottonoid application is not recommended.

Tumor Necrosis Factor-induced Decrease of Cochlear Blood Flow Can Be Reversed by Etanercept or JTE-013.

This study aimed to quantify the effects of tumor necrosis factor (TNF) inhibitor Etanercept and sphingosine-1-phosphate receptor 2 antagonist JTE-013 on cochlear blood flow in guinea pigs after TNF-induced decrease. Sudden sensorineural hearing loss is a common cause for disability and reduced quality of life. Good understanding of the pathophysiology and strong evidence-based therapy concepts are still missing. In various inner ear disorders, inflammation and impairment of cochlear blood flow (CBF) have been considered factors in the pathophysiology. A central mediator of inflammation and microcirculation in the cochlea is TNF. S1P acts downstream in one TNF pathway. Cochlea lateral wall vessels were exposed surgically and assessed by intravital microscopy in guinea pigs in vivo. Twenty-eight animals were randomly distributed into four groups of seven each. Exposed vessels were superfused by TNF (5.0 ng/ml) and afterward repeatedly either by Etanercept (1.0 μg/ml), JTE-013 (10 μmol/L), or vehicle (0.9 % NaCl solution or ethanol: phosphate-buffered saline buffer, respectively). After decreasing CBF with TNF (p <0.001, two-way RM ANOVA), both treatments reversed CBF, compared with vehicle (p <0.001, two-way RM ANOVA). The comparison of the vehicle groups showed no difference (p = 0.969, two-way RM ANOVA), while there was also no difference between the treatment groups (p = 0.850, two-way RM ANOVA). Both Etanercept and JTE-013 reverse the decreasing effect of TNF on cochlear blood flow and, therefore, TNF and the S1P-signalling pathway might be targets for treatment of microcirculation-related hearing loss.

Vasospasm of labyrinthine artery in cerebellopontine angle surgery: evidence brought by distortion-product otoacoustic emissions

In cerebellopontine angle (CPA) surgery, postoperative deafness can be due to alteration of cochlear blood flow that is supplied by the labyrinthine artery (LA). In particular, vasospasm is likely to occur and, if so, can be reversed. This work attempted to track down vascular events occurring during CPA surgery. Twenty consecutive patients with vestibular schwannoma were tested with useful preoperative hearing and presence of otoacoustic emissions (OAEs). Distortion-product otoacoustic emissions (DPOAEs), well-known to react within seconds to cochlear ischemia, were used intraoperatively to indirectly monitor cochlear blood flow. Continuous intraoperative monitoring of DPOAEs revealed three different time patterns associated with distinct auditory outcomes. Pattern P1-acute (n = 4) happened when the LA was severed: DPOAEs immediately and irreversibly foundered and led to postoperative deafness. Pattern P2-protracted (n = 7) revealed a progressive deterioration of DPOAEs from the beginning of tumor debulking, likely due to a steady decrease of cochlear blood flow, with postoperative deafness. Pattern P3-unstable (n = 5) corresponded to large DPOAE oscillations between their normal level and noise floor. It was due to acute LA vasospasm that could be reversed in three cases by topical nimodipin. Last, four patients had uneventful cochlear monitoring. In conclusion, cochlear ischemia can occur in vestibular schwannoma surgery, giving three different patterns among which vasospasm can be reversed if detected early.

Effects of different doses of propofol or isoflurane on cochlear blood flow in guinea pigs

Objective To evaluate the effects of different doses of propofol or isoflurane on the cochlear blood flow (CBF) in guinea pigs.Methods Fifty-four adult male guinea pigs,aged 3 months,weighing 400-500 g,were randomly divided into 6 groups (n =9 each).In P1,P2 and P3 groups,propofol was infused for 115 min at 10,20 and 40 mg· kg-1 · h-1,respectively,after a loading dose of 5 mg/kg was injected over 5 min.In S1,S2 and S3 groups,isoflurane was inhaled for 120 min with end-tidal concentrations of 1％,2％ and 3 ％,respectively.Mean arterial pressure and CBF were recorded before administration (baseline,T1) and during the period of drug administration.Distortion product otoacoustic emission (DPOAE) was measured at T1,at the end of administration (T2) and 1 h after administration (T3).Five animals in each group were sacrificed and organs of Corti were harvested for observation of morphology of out hair cells by scanning electron microscopy.Results Propofol decreased MAP and increased CBF and DPOAE amplitude in a dose-dependent manner.Isoflurane decreased MAP and CBF in a dose-dependent manner.1％ isoflurane increased DPOAE amplitude,however,2％ and 3％ isoflurane decreased it and caused damage to out hair cells.Conclusion Propofol induces an increase in CBF in guinea pigs,while high concentration of isoflurane induces a decrease in CBF.Isoflurane inhibits CBF autoregulation,which makes CBF more sensitive to perfusion pressure,thus causing damage to hearing function.This is the reason why high concentration of isoflurane induces a decrease in CBF. Key words: Propofol ; Isoflurane ; Cochlea ; Regional blood flow ; Auditory perception

Etanercept Prevents Decrease of Cochlear Blood Flow Dose-Dependently Caused by Tumor Necrosis Factor Alpha

Tumor necrosis factor alpha (TNF-alpha) is a mediator of inflammation and microcirculation in the cochlea. This study aimed to quantify the effect of a local increase of TNF-alpha and study the effect of its interaction with etanercept on cochlear microcirculation. Cochlear lateral wall vessels were exposed surgically and assessed by intravital microscopy in guinea pigs in vivo. First, 24 animals were randomly distributed into 4 groups of 6 each. Exposed vessels were superfused repeatedly either with 1 of 3 different concentrations of TNF-alpha (5.0, 0.5, and 0.05 ng/mL) or with placebo (0.9% saline solution). Second, 12 animals were randomly distributed into 2 groups of 6 each. Vessels were pretreated with etanercept (1.0 microg/ mL) or placebo (0.9% saline solution), and then treated by repeated superfusion with TNF-alpha (5.0 ng/mL). TNF-alpha was shown to be effective in decreasing cochlear blood flow at a dose of 5.0 ng/mL (p < 0.01, analysis of variance on ranks). Lower concentrations or placebo treatment did not lead to significant changes. After pretreatment with etanercept, TNF-alpha at a dose of 5.0 ng/mL no longer led to a change in cochlear blood flow. The decreasing effect that TNF-alpha has on cochlear blood flow is dose-dependent. Etanercept abrogates this effect.

Matrix metalloproteinase inhibitor attenuates cochlear lateral wall damage induced by intratympanic instillation of endotoxin

Oxytetracycline and ilomastat are inhibitors of matrix metalloproteinases (MMPs). Their efficacy in protecting against cochlear damage induced by the intratympanic instillation of lipopolysaccharide (LPS), as a means of inducing labyrinthitis, was investigated. Experiments were performed in 21 young male guinea pigs. Intratympanic instillation of LPS was done in the control group (n=7). Intratympanic instillation of oxytetracycline or ilomastat was done after LPS instillation in the experimental group. Measurements of auditory brainstem response (ABR) and cochlear blood flow (CBF) were performed. The organ of Corti was evaluated by field emission scanning electron microscopy (FE-SEM). The blood-labyrinth barrier (BLB) integrity was evaluated with Evans blue uptake. Gelatin zymography was used to assess the expression of active MMP-2 and MMP-9. Ears treated with MMP inhibitors were significantly protected from hearing loss compared to the LPS group. In LPS group, there was a significant decrease of CBF. However, experimental group displayed a statistically significant recovery of CBF. FE-SEM revealed hair cell damage in the LPS-treated group, but hair cells presented a normal appearance in MMP inhibitors. The LPS group showed a marked increase of Evans blue extravasation in the cochlea. However, MMP inhibitors significantly reduced the BLB opening. Active MMP-9 was expressed in the LPS group. Treatment with MMP inhibitors attenuated active MMP-9 expression. The MMP inhibitors oxytetracycline and ilomastat protect from cochlear lateral wall damage caused by LPS-induced labyrinthitis.

Cochlear blood flow during occlusion and reperfusion of the anterior inferior cerebellar artery – effect of topical application of dexamethasone to the round window

Conclusion. Topical application of dexamethasone may support autoregulation of cochlear blood flow (CBF), although it had no direct effect on CBF. Objectives. Although intratympanic steroid therapy for patients with inner ear disorders is common, the mechanism by which steroids exert their effect is unclear. We investigated the response of CBF to topical application of dexamethasone onto the round window. Materials and methods. Two concentrations of dexamethasone (3.3 mg/ml and 33 mg/ml dexamethasone in 0.5 µl saline) were applied to the round windows of rats, and CBF responses were measured using a laser Doppler flowmeter. The effects on CBF of a 2 h occlusion of the anterior inferior cerebellar artery (AICA) and subsequent release of the clamp with or without previous dexamethasone application were investigated. Results. No significant change in CBF was observed after topical application of dexamethasone, and it did not affect the decrease in CBF caused by AICA occlusion. However, recovery of CBF after release of the AICA clamp was better in animals treated with dexamethasone than in those that did not receive dexamethasone.

A model of real time monitoring of the cochlear function during an induced local ischemia

The aim of this study was to investigate the utility of distortion product otoacoustic emissions (DPOAEs) in intraoperative monitoring (IM) of cochlear ischemic episodes in animals during internal auditory artery (IAA) compression. The IAA was exposed using the posterior fossa approach and then compressed for 3 and 5 min intervals to effect ischemia. DPOAE amplitudes and phases were measured at 4, 8, and 12 kHz geometric mean frequency (GMF). In each monitored ear, laser-Doppler cochlear blood flow (CBF) was measured. All IAA compressions resulted in rapid decrease of DPOAE amplitude and CBF, with simultaneous DPOAE phase increase. DPOAE phase changes were found to increase consistently within several seconds of IAA compression, while corresponding DPOAE amplitudes changed more slowly, with up to 30-40 s delays. Following IAA release, DPOAEs at 12 kHz GMF were characterized by longer delays in returning to baseline than those measured at lower frequencies. In some cases, CBF did not return to baseline. In this animal model, DPOAEs were found to be sensitive measures of cochlear function during transient cochlear ischemic episodes, suggesting the utility of DPOAE monitoring of auditory function during surgery of cerebello-pontine angle tumors.

Changes in cochlear blood flow due to endotoxin-induced otitis media.

The purpose of this study was to elucidate the influence of otitis media on blood flow in the lateral wall of the cochlea by means of a model of endotoxin-induced otitis media. The cochlear blood flow (CBF) following lipopolysaccharide inoculation into the middle ear cavities of rats was measured by laser-Doppler flowmetry and compared with that of untreated ears. After this evaluation, the influence on CBF of concomitant use of a nitric oxide synthase inhibitor was also investigated. The first day after inoculation, the CBF of treated ears decreased significantly. This decrease recovered gradually between the 7th and 14th days. With concomitant use of a nitric oxide synthase inhibitor, the decrease in CBF was prevented to some extent. The results showed a functional influence upon CBF by endotoxin-induced otitis media. The significance of prophylactic use of the drug is also discussed in regard to the effect on CBF following otitis media.

Cochlear Blood Flow Modifications Induced by Anaesthetic Drugs in Middle Ear Surgery: Comparison Between Sevoflurane and Propofol

Objective --Because it is necessary to maintain controlled hypotension during middle ear surgery in order to avoid bleeding and as it is known that cochlear blood flow (CBF) is related to blood pressure (BP), it is useful to evaluate CBF modifications induced by anaesthetics in order to prevent cochlear damage. The aim of this paper is to evaluate, using laser Doppler flowmetry, which anaesthetic drug, out of sevoflurane and propofol, has the smallest effect on CBF. Material and Methods --Twenty consenting adult patients scheduled for myringoplasty under general anaesthesia for simple tympanic membrane perforation were studied. Patients were divided into two groups: the first group was treated with sevoflurane and the second with propofol. For the first group, CBF measurement was carried out on three different occasions: (i) at a basal low drug dosage; (ii) having increased the drug dosage to a higher level; and (iii) having reduced the drug dosage to the basal low level again. For the second group, CBF measurement was carried out on three different occasions: (i) 10 min after injecting a bolus of propofol; (ii) immediately after a second propofol injection; and (iii) 10 min after a third injection of propofol. A probe was placed over the promontory in order to measure CBF levels. Results --In the subjects treated with sevoflurane, after having increased the drug dosage, BP decreased significantly while CBF did not change significantly. In the subjects treated with propofol we recorded a significant reduction in BP, as well as a decrease in CBF. Conclusion --The results obtained show that sevoflurane has a hypotensive effect without modifying CBF, while propofol, although having a similar effect on BP to sevoflurane, has less of a protective effect on inner ear microcirculation.

Effects of round window membrane rupture on cochlear blood flow and endocochlear potential

The degree of hearing loss and audiogram shape vary in patients with perilymphatic fistula. The cause of variability is not well known. To determine the effect of perilymphatic fistula on cochlear function, we studied the effect of round window membrane rupture on cochlear blood flow (CBF) by placing a laser-Doppler probe to the basal turn in 20 guinea pigs. In 10, endocochlear potential (EP) was measured by inserting a glass microelectrode through the stria vascularis of the basal turn. During 60 minutes following round window membrane rupture, CBF decrease of more than 15% was observed in 9 of 20 animals, and EP decrease of more than 15% was observed in 5 of 10. A significant correlation was observed between the degree of CBF reduction and EP reduction. In 3 animals in which CBF decreased after round window membrane rupture, temporal bones were studied histologically. One cochlea showed endolymphatic hydrops and another cochlea showed significant hemorrhage in the scala tympani after rupture. These results suggested that CBF impairment is associated with cochlear dysfunction in perilymphatic fistula.

Effects of nimodipine on salicylate ototoxicity.

The purpose of this study was to examine the effects of nimodipine on salicylate ototoxicity in guinea pigs. The compound action potential (CAP) was recorded at the round window, and the cochlear blood flow (CBF) was measured simultaneously from the lateral wall of the basal turn of the cochlea by laser Doppler flowmetry. After administration of salicylate (100 mg/kg), the CAP thresholds were significantly elevated, by 5 to 20 dB (p < .05), and the CBF was significantly decreased (p < .05). After administration of nimodipine (2 mg/kg), the CAP thresholds were unchanged, but the CBF had increased significantly (p < .05), while systemic blood pressure had decreased significantly (p < .05). Simultaneous administration of both salicylate (100 mg/kg) and nimodipine (2 mg/kg) resulted in significant elevation of the CAP thresholds (p < .05), while the CBF did not decrease. These results suggest that nimodipine prevents the decrease in CBF induced by salicylate, but that nimodipine does not prevent the deterioration in the CAP.

Decrease in Cochlear Blood Flow with Infusion of Nitric Oxide Synthase Inhibitor and its Recovery with L-arginine Infusion: Comparison with Abdominal Blood Flow and Auricular Blood Flow

We observed changes in cochlear blood flow (CoBF), abdominal blood flow (AbBF) and auricular blood flow (AuBF) in rats after administration of the nitric oxide (NO) synthase inhibitor N-nitro-L-arginine-methyl ester (L-NAME). Ten min after i.v. infusion of L-NAME, L-arginine, a substrate of NO, was infused (100 mg/kg) intravenously. Using a laser Doppler flowmeter, changes in blood flow were recorded from the basal turn of the right cochlea, abdominal wall or right auricle, and systemic blood pressure (BP) was recorded simultaneously from the left femoral artery. As another parameter of vascular response, vascular conductance (VC) was calculated from blood flow/mean BP. I.v. infusion of L-NAME produced a dose-dependent depression of cochlear VC at concentrations of 0.2 (-18.9%), 1 (-37.9%), 5 (-45.8%) and 10 mg/kg (-48.3%). Infusion of L-arginine partially reversed the decrease of CoBF caused by L-NAME. The group that received a 0.2 mg/kg infusion of L-NAME showed the largest degree of recovery (23.8%) with L-arginine, while the 10 mg/kg group showed the smallest degree of recovery (10.1%). AbBF also decreased after infusion of L-NAME (5 mg/kg) but to a lesser degree (-41.1% depression of VC) and with no significance compared to the decrease in CoBF (5 mg/kg L-NAME). Likewise, AuBF showed a decrease (-44.0% depression of VC) after infusion of L-NAME (10 mg/kg), the decrease being less than that of CoBF (10 mg/kg L-NAME). Recoveries from these decreased levels of VC in the AbBF and AuBF groups appeared to be smaller than those in the CoBF groups at the same dose of L-NAME (5.5% vs 17.3% in abdominal VC; 5.3% vs 10.1% in auricular VC). In a previous study comparing the CoBF changes caused by i.v. infusion and round window application of L-NAME, we proposed that i.v. infusion of L-NAME in rats primarily affects the precapillary arteriole of the spiral modiolar artery, which effectively regulates cochlear microcirculation as a resistance artery. Thus we assume that there may exist an active pathway of the NO/soluble guanylate cyclase/cyclic guanosine monophosphate system in the above vessels. With regard to the finding of a smaller recovery of VC with L-arginine in both the AbBF and AuBF groups, we consider that differences in L-arginine availability or uptake, and in the synthesis of NO, may exist between the cochlear and cutaneous vasculatures.

Decrease in Cochlear Blood Flow with Infusion of Nitric Oxide Synthase Inhibitor and its Recovery with L-arginine Infusion: Comparison with Abdominal Blood Flow and Auricular Blood Flow

We observed changes in cochlear blood flow (CoBF), abdominal blood flow (AbBF) and auricular blood flow (AuBF) in rats after administration of the nitric oxide (NO) synthase inhibitor N-nitro-L-arginine-methyl ester (L-NAME). Ten min after i.v. infusion of L-NAME, L-arginine, a substrate of NO, was infused (100 mg/kg) intravenously. Using a laser Doppler flowmeter, changes in blood flow were recorded from the basal turn of the right cochlea, abdominal wall or right auricle, and systemic blood pressure (BP) was recorded simultaneously from the left femoral artery. As another parameter of vascular response, vascular conductance (VC) was calculated from blood flow/mean BP. I.v. infusion of L-NAME produced a dose-dependent depression of cochlear VC at concentrations of 0.2 (-18.9%), 1 (-37.9%), 5 (-45.8%) and 10 mg/kg (-48.3%). Infusion of L-arginine partially reversed the decrease of CoBF caused by L-NAME. The group that received a 0.2 mg/kg infusion of L-NAME showed the largest degree of recovery (23.8%) with L-arginine, while the 10 mg/kg group showed the smallest degree of recovery (10.1%). AbBF also decreased after infusion of L-NAME (5 mg/kg) but to a lesser degree (-41.1% depression of VC) and with no significance compared to the decrease in CoBF (5 mg/kg L-NAME). Likewise, AuBF showed a decrease (-44.0% depression of VC) after infusion of L-NAME (10 mg/kg), the decrease being less than that of CoBF (10 mg/kg L-NAME). Recoveries from these decreased levels of VC in the AbBF and AuBF groups appeared to be smaller than those in the CoBF groups at the same dose of L-NAME (5.5% vs 17.3% in abdominal VC; 5.3% vs 10.1% in auricular VC). In a previous study comparing the CoBF changes caused by i.v. infusion and round window application of L-NAME, we proposed that i.v. infusion of L-NAME in rats primarily affects the precapillary arteriole of the spiral modiolar artery, which effectively regulates cochlear microcirculation as a resistance artery. Thus we assume that there may exist an active pathway of the NO/soluble guanylate cyclase/cyclic guanosine monophosphate system in the above vessels. With regard to the finding of a smaller recovery of VC with L-arginine in both the AbBF and AuBF groups, we consider that differences in L-arginine availability or uptake, and in the synthesis of NO, may exist between the cochlear and cutaneous vasculatures.

Effects of corticosteroid, contrast medium and ATP on focal microcirculatory disorders of the cochlea

We evaluated the ability of various drugs to prevent the decrease in focal cochlear blood flow induced by photochemical reaction and investigated the mechanisms underlying this decrease. By means of a photochemical reaction, which produces reactive oxygen species, focal lesions measuring about 1 mm in diameter were induced in the lateral wall of the guinea pig cochlea. The protective effects of hydrocortisone, amidotrizoate and ATP on cochlear blood flow and cochlear vascular conductance changes were evaluated by using a non-contact laser flowmeter. Cochlear blood flow and cochlear vascular conductance were decreased to 65.1+/-4.9% (mean +/- S.E.M.) and 57.0+/-3.7% (mean +/- S.E.M.) of the initial level 30 min after the start of the photochemical reaction, respectively. Hydrocortisone significantly prevented the decline in the cochlear blood flow and cochlear vascular conductance and reduced the area of stria vascularis degeneration in a dose-dependent manner. Neither amidotrizoate nor ATP significantly prevented the decrease in cochlear blood flow or cochlear vascular conductance. Hydrocortisone was more effective than vasodilators or other agents which increase cochlear blood flow in preventing the photochemically induced decrease in cochlear blood flow. This might be due to the antioxidative effects of hydrocortisone.

Management of Idiopathic Sudden Sensorineural Hearing Loss

The cause of sudden sensorineural hearing loss (SHL) remains unknown, even though studies have evidenced two main hypotheses: a latent virus infection due to herpesvirus and a local decrease in cochlear blood flow caused by vasospasm and/or hyperviscosity. Clinical evaluation and diagnostic tests should always be performed, to rule out an acoustic neuroma, revealed in 5–26% of cases by a sudden deafness. The two main major prognostic factors are the severity of hearing loss and the time from onset to treatment, suggesting that two groups of patients are susceptible to benefit from therapy: patients with a hearing loss of less than 40 dB, managed within 2 months from the onset, and patients with a hearing loss of more than 40 dB, treated within 1 month after the onset of deafness. Steroids appear to be the only treatment available with a significant beneficial effect on SHL.