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Purpose: To corroborate the vascular etiology of sudden sensorineural hearing loss (SNHL) utilizing magnetic resonance imaging (MRI)., Patient: A 24-year-old male with a history of sickle cell disease experienced sudden SNHL and right horizontal nystagmus, without accompanying vertigo., Intervention: Audiometric evaluation revealed left-sided SNHL, predominantly affecting high frequencies. Video head impulse testing demonstrated isolated dysfunction of the left posterior semicircular canal. An urgent brain MRI identified a recent punctiform ischemic stroke in the frontal region. A subsequent MRI, conducted with a 4-hour delay and post-contrast enhancement, highlighted a hyperintense signal within the left cochlear region and the left posterior semicircular canal., Conclusion: The investigative results substantiate an infarction in the territory of the cochlear artery, precipitated by a vaso-occlusive event, thereby reinforcing the vascular hypothesis of cochleovestibular artery syndrome. This case underscores the congruence between clinical observations and delayed post-contrast MRI findings., Competing Interests: Declarations Conflict of interest None., (© 2024. The Author(s).)

In vestibular-schwannoma (VS) surgery, hearing-preservation rate remains low. Besides damage to the cochlear nerve, intraoperative cochlear ischemia is a potential cause of hearing loss. Here, we used non-invasive cochlear microphonic (CM) recordings to detect the cochlear vascular events of VS surgery. Continuous intraoperative CM monitoring, in response to 80-95 dB SPL, 1-kHz tone-bursts, was performed in two samples of patients undergoing retrosigmoid cerebellopontine-angle surgery: one for VS (n = 31) and one for vestibular neurectomy or vasculo-neural conflict causing intractable trigeminal neuralgia, harmless to hearing (n = 19, control group). Preoperative and postoperative hearings were compared as a function of intraoperative CM changes and their chronology. Monitoring was possible throughout except for a few tens of seconds when drilling or suction noises occurred. Four patterns of CM time course were identified, eventless, fluctuating, abrupt or progressive decrease. Only the VS group displayed the last two patterns, mainly during internal-auditory-canal drilling and the ensuing tumor dissection, always with postoperative loss of hearing as an end result. Conversely, eventless and fluctuating CM patterns could be associated with postoperative hearing loss when the cochlear nerve had been reportedly damaged, an event that CM is not meant to detect. Cochlear ischemia is a frequent event in VS surgery that leads to deafness. The findings that CM decrease raised no false alarm, and that CM fluctuations, insignificant in control cases, were easily spotted, suggest that CM intraoperative monitoring is a sensitive tool that could profitably guide VS surgery.

The patency of the inferior cochlear vein (ICV) may be challenged in cochlear implantation (CI) due to its location near the round window (RW). This may be essential to consider during selection of different trajectories for electrode insertion aiming at preserving residual hearing. Venous blood from the human cochlea is drained through the ICV. The vein also drains blood from the modiolus containing the spiral ganglion neurons. Surgical interference with this vein could cause neural damage influencing CI outcome. We analyzed the topographical relationship between the RW and ICV bony channel and cochlear aqueduct (CA) from a surgical standpoint. Archival human temporal bones were further microdissected to visualize the CA and its accessory canals (AC1 and AC2). This was combined with examinations of plastic and silicone molds of the human labyrinth. Metric analyses were made using photo stereomicroscopy documenting the proximal portion of the AC1, the internal aperture of the CA and the RW. The mean distance between the AC1 and the anterior rim of the RW was 0.81 mm in bone specimens and 0.67 mm assessed in corrosion casts. The AC1 runs from the floor of the scala tympani through the otic capsule passing parallel to the CA to the posterior cranial fossa. The mean distance between the CA and AC1 canal was 0.31 and 0.25 mm, respectively.

Purpose: The purpose of this investigation was to evaluate the topographic relations of cochlea with vital neurovascular structures and their implications for cochlear implantation (CI)., Methods: Sixty cadaveric human temporal bones were microdissected to expose the basal turn (BT) of cochlea, the carotid canal, the facial canal (FC) and the jugular fossa (JF). The minimum distances of BT of the cochlea from the carotid canal, the FC and roof of the JF were measured., Results: The mean minimum distances of BT of the cochlea from the carotid canal, the FC and roof of the JF were found to be 1.38 ± 0.82, 1.06 ± 0.46 and 4.68 ± 2.21 mm, respectively. The abutment and impingement of carotid canal on anterior cochlear wall was found in three (5 %) and six (10 %) cases, respectively. Thin bone separation was observed between cochlea and FC (0.1 mm) in one case (1.67 %)., Conclusions: The preoperative knowledge of the variant anatomy of BT of cochlea in relation to adjacent vital structures like abutment and impingement of carotid canal and thin bone separation of the BT of cochlea from FC and JF is of immense importance in CI, which may otherwise lead to disastrous consequences during surgery.

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.

An impaired cochlear perfusion seems to be an important etiopathogenetic event in idiopathic sudden sensorineural hearing loss (ISSNHL). Recently, oxidative stress has been proposed as risk factors of microvascular damage. This observational study aimed to evaluate the possible role of oxidative stress in ISSNHL. In thirty-nine ISSNHL patients and seventy healthy subjects serum reactive oxygen species concentrations (ROS) and total antioxidant capacity (TAC) were measured by spectrophotometric methods on F.R.E.E. analyzer (Diacron International, Italy). Moreover, a global oxidative stress index (Oxidative-INDEX), reflecting both oxidative and antioxidant counterparts, was also calculated. 25/39 patients showed oxidative stress due to ROS levels significantly higher than controls (348.2 ± 84.8 vs. 306.75 ± 46.7 UCarr; p = 0.001). The Oxidative-INDEX was significantly higher in patients than in controls (0.75 ± 2.4 vs. -0.0007 ± 1.28 AU, p = 0.03). As oxidative stress is a key determinant in endothelial dysfunction, our findings could suggest vascular impairment involvement in ISSNHL etiopathogenesis.

Impairment of cochlear blood flow (CBF) is considered to be important in inner ear pathology. However, direct measurement of CBF is difficult and has not been investigated in combination with hearing function. Six guinea pigs were used to show feasibility of an animal model for the analysis of cochlear microcirculation by intravital microscopy in combination with investigation of the hearing threshold by brainstem response audiometry (ABR). By the application of sodium nitroprusside (SNP), CBF was increased over 30 min. Reproducibility of measurements was shown by retest measurements. Mean baseline velocity of CBF was 109 +/- 19 mum/s. Vessel diameters had a mean value of 9.4 +/- 2.7 mum. Mean hearing threshold was 19 +/- 6 dB. In response to SNP, CBF velocity increased significantly to 161 +/- 26 mum/s. Mean arterial pressure decreased significantly to 36 +/- 11 mmHg. After the end of the application, CBF velocity recovered to a minimum of 123 +/- 17 microm/s. Within the retest, CBF velocity significantly increased to a maximum of 160 +/- 31 microm/s. Second recovery of CBF velocity was 125 +/- 14 mum/s. Within the second retest, CBF increased significantly to 157 +/- 25 microm/s. ABR thresholds did not change significantly. The increase in blood flow velocity occurred in spite of substantial hypotension as induced by a vasodilator. This may explain the fact that ABR threshold remained unchanged reflecting a maintained blood supply in this part of the brain. This technique can be used to evaluate effects of treatments aimed at cochlear microcirculation in inner ear pathologies.

Currently, the treatment of sudden deafness (SD) is based mainly on complete bed rest and the administration of corticosteroids. Hyperbaric oxygen therapy (HBOT) has previously been suggested as adjunctive treatment. We describe two cases of successful HBOT for SD. The first patient presented with moderate mid-frequency hearing loss without accompanying symptoms, whereas the second patient had moderate low-frequency hearing loss with persistent tinnitus and a single episode of vertigo. HBOT in addition to conventional treatment soon after diagnosis resulted in full recovery of hearing in both patients. The pathogenesis of SD may involve a reduction in cochlear blood flow and perilymph oxygenation, making early HBOT a reasonable treatment modality for this condition.

Prostaglandin E(1) (PGE(1)), a vasodilator and an inhibitor of platelet aggregation, has been used for the treatment of idiopathic sudden sensorineural hearing loss, despite the fact that its effectiveness has not been proven. Furthermore, it is rapidly metabolized in the lungs, which makes it difficult to use clinically. In an attempt to prevent this, PGE(1) was coated with a 0.2-microg lipid microsphere produced by beans; this was designated lipo-PGE(1). This coating protects PGE(1) from being rapidly metabolized. In this study, the effectiveness of the intravenous administration of lipo-PGE(1) was compared with that of PGE(1) by investigating the effects on systemic blood pressure (SBP) and cochlear blood flow (CBF) in guinea pigs with normal ears. The results of both drugs showed a dose-dependent decrease in SBP and the maintenance of CBF despite the decrease in SBP. However, no significant increase in CBF was observed for either drug. In comparing the effects of PGE(1) and lipo-PGE(1), no obvious differences in the effects on SBP and CBF were observed in this study.

Use of laser Doppler flowmetry (LDF) to assess cochlear blood flow (CBF) in experimental animals has elucidated the complex mechanisms in CBF regulation. Some attempts have been made to measure CBF in humans, although earlier studies produced confusing data about the physical possibility of LDF penetrating the human tympanic cavity promontory. In this study, we used LDF in an attempt to observe capillary blood flow in vivo through the intact human promontory in order to develop a method for measuring CBF in human patients. Temporal bones from six human cadavers were removed and the promontory overlying the basal turn of the cochlea was drilled off and fixed in 10% formalin. Perpendicular bone thickness was measured at the site of the stria vascularis. Seven young rats were anesthetized and the carotid artery was cannulated for blood pressure recording. Capillary flow was registered with LDF from two sites, the kidney and the plantar area of a hind limb, using a custom-designed probe with 632.8 nm and 780 nm wavelengths. Intravenous epinephrine was used to evoke blood flow changes. The same measurements were repeated through the promontorial bone. The light attenuation induced by the promontorial bone was 79+/-28% for the 632.8 nm wavelength, and 22+/-15 to 65+/-13% for the 780 nm wavelength, depending on the thickness of the bone. The sensitivity in detecting minute changes was 78% and 91-96%, respectively, for the 632.8 nm and 780 nm wavelengths. This study indicates that it is possible to detect minute changes in capillary blood flow through the intact human promontory at the site of the stria vascularis.

The effect of magnesium (Mg) on ischemia-induced hearing loss was investigated in two groups of adult pigmented guinea pigs of either an optimal or suboptimal (physiologically high or low) Mg status maintained by different diets. Total Mg concentrations of the perilymph, cerebrospinal fluid, blood plasma and red blood cells were found to differ significantly between the two groups, as tested in a previous study. Local vascular impairment was produced by unilateral ferromagnetic thrombosis of cochlear blood vessels. Cochlear blood flow (CBF) and hearing function were measured using laser Doppler flowmetry and auditory brain-stem response audiometry, respectively. Ferromagnetic thrombosis resulted in significant reductions of the mean apical CBF in both experimental groups and of the mean basal CBF in the low Mg group compared to the contralateral ears. In the high Mg group, the basal CBF was not decreased. However, the laser Doppler signals revealed considerable interindividual variations and the differences found between the two experimental groups were not significant. In contrast, the hearing loss in the low Mg group was significantly higher than that in the high Mg group. A correlation was found to exist between the vascular impairment and the hearing threshold shift. In a separate series, we also tested the effect of Mg on hemorheology and found both the blood viscosity and blood viscoelasticity to be significantly lower in the high Mg group than in the low Mg group, depending on the shear rates tested. The present findings show that a preventive oral Mg supplement can significantly reduce the rate of ischemia-induced hearing loss and improve blood viscosity in the guinea pig.

Hearing loss (HL) is a rare complication following cardiac surgery with extracorporal circulation (CSWEC) or other non-otologic surgery under general anesthesia, as is HL caused by loss of cerebrospinal fluid during neurosurgery or spinal anesthesia. The incidence of HL after CSWEC is not known since preoperative hearing testing is not commonly done and a perioperative HL may occur unnoticed. We present four cases of profound sensorineural hearing loss following CSWEC for coronary artery bypass or cardiac valve surgery. The hearing loss was noticed immediately on waking from anesthesia in three of the patients, whereas the fourth patient noticed decreased hearing during the first postoperative week. In all patients audiological investigation suggested a cochlear etiology of the HL. The possible mechanisms for HL are discussed. HL after CSWEC is most likely caused by a microembolism generated by atheromatous material.

The effects of glycerol on cochlear blood flow and serum osmotic pressure were studied in healthy guinea pigs. Laser Doppler flowmetry of cochlear blood flow after the esophageal-gastric administration of 50% glycerol demonstrated a greater increase in blood flow for a longer time than with the intravenous infusion of 50% glycerol. The intravenous infusion of glycerol did increase systemic blood pressure, which changed partially in parallel with the change in cochlear blood flow. The change in systemic blood pressure after esophageal-gastric administration was slight. In another experiment designed to observe the changes in serum osmotic pressure after glycerol administration, the esophageal-gastric route also caused a greater and longer increase in serum osmolarity than intravenous infusion. The increase in cochlear blood flow after glycerol administration was thought to be due to an increase in the osmotic gradient between the blood in the cochlear vessels and the interstitial fluid, or to the high osmolarity of the blood itself. The possible mechanisms underlying local blood flow increase caused by high serum osmolarity are discussed. Systemic blood pressure increase induced by glycerol could be an influential factor for the cochlear blood flow increase during intravenous infusion.

Prostaglandins (PGs) such as PGE2 and PGI2 are vasodilators, and leukotrienes (LTs) such as LTB4 and LTC4 are vasoconstrictors. Our previous studies have shown that salicylate ototoxicity is associated with decreased levels of PGs and increased levels of LTs. We hypothesized that vasodilating PGs increase cochlear blood flow and vasoconstricting LTs decrease cochlear blood flow. PGE2, Iloprost (a PGI2 analog), LTB4, and LTC4 were applied to the round window membranes of chinchillas and cochlear blood flow was measured with a laser Doppler flowmeter. PGE2 increased cochlear blood flow, while LTC4 decreased cochlear blood flow. This findings show that vasodilating PGs may have therapeutic implications for sensorineural hearing loss and/or vertigo by increasing cochlear blood flow. Vasoconstricting LTs may cause hearing loss by decreasing cochlear blood flow.

The aim of this study was to investigate the mechanism and site of action of betahistine dihydrochloride in the inner ear of the guinea pig. Betahistine-evoked increases in cochlear blood flow (CBF) have been presumed to be due to the drug effect on the later wall capillary bed or larger feeding vessels in the cochlea vascular system. As such, the mechanism of action could be due to inhibition of H3 receptors. Betahistine may also have a direct effect on postsynaptic H1/H2 receptors and/or an effect modulated by other autonomic receptors. Betahistine-evoked CBF responses were assessed by laser Doppler flowmetry in the presence of an H3 agonist (alpha N-methyl-histamine dihydrochloride), an H3 antagonist (thioperamide), an H2 antagonist (cimetidine) or an alpha 2 antagonist (idazoxan). The effects of betahistine on circulation in the anterior inferior cerebellar artery (AICA) and ipsilateral stria vascularis (SV) were assessed using intravital microscopy (IVM). Findings showed that betahistine increased CBF and reduced systemic blood pressure (BP). In contrast, alpha N-methylhistamine dihydrochloride had no effect on baseline CBF or BP and did not influence betahistine-induced increases in CBF. Thioperamide reversed the effects of betahistine on CBF, but had no effect on baseline CBF or BP. Cimetidine had no marked effect on baseline CBF or betahistine-induced increases in CBF Idazoxan had no consistent effects on baseline CBF, but abolished the effect of betahistine on CBF. The mean increase of red blood cell velocity in SV capillaries was 15% and occurred without a demonstrable change in capillary diameters. In contrast, the diameter of the AICA increased by 17-20%, indicating that betahistine-evoked increases in CBF resulted primarily from vasodilatation of the AICA. We suggest that this effect may be mediated via presynaptic H3 heteroreceptors and autonomic alpha 2 receptors.

The nitric oxide (NO) donor sodium nitropruside (SNP) applied to the round window membrane has recently been found to increase cochlear blood flow (CoBF) in normal guinea pigs and in normal and presbyacusic mice. This study examined the effect of topical applications of SNP on experimentally impaired CoBF in anesthetized guinea pigs. Small (3 microliters) portions of 3% SNP were applied to the round window niche of both normal and thrombosed cochleas. Local vascular impairment was produced by ferromagnetic thrombosis of cochlear blood vessels and the microcirculation measured using laser Doppler flowmetry. Ferromagnetic thrombosis resulted in a mean decrease of CoBF to 52% of baseline. There was a clear improvement in mean CoBF to 84% of baseline by the topical application of SNP that depended on the degree of ischemic damage produced. Under neuroleptanalgesia and ketamine-xylazine anesthesia, significant increases in CoBF were measured in normal ears as well as in the thrombosed ones. However, several SNP applications were needed to improve the impaired CoBF, while a single portion was sufficient in the normal cochlea to cause a drastic increase in mean CoBF to 234% of baseline. In urethane-anesthetized animals, no flow increase was found despite repeated drug administration. Careful evaluation of the laser Doppler signals was necessary to accurately determine the concentrations of the moving blood cells and their mean velocities.

Hemodilution is considered to be a useful therapy for sudden hearing loss by improving cochlear blood flow (COBF) as a result of decreasing viscosity of the whole blood. The purpose of this investigation was to evaluate whether hemoconcentration actually leads to a diminished COBF and impaired function of the cochlea to thus play a role in the pathogenesis of sudden hearing loss. Ten New Zealand White rabbits were anesthetized and ventilated. Cochlear function was evaluated by measuring distortion products of otoacoustic emissions (DPOAEs) at the beginning of each experiment and after 120 min. In the interim, each test animal's hematocrit was raised by an infusion of packed red cells. Control animals were not infused, so hematocrits were left unchanged. Reproducibility of DPOAE measurements were found to be dependent upon the stimulus level. Correlation coefficients were 0.83 for 65 dB SPL and 0.78 for 45 dB SPL. Although no changes in the absolute level of DPOAEs were observed after raising the hematocrit, correlation coefficients were diminished to 0.68 at 65 dB SPL and 0.58 at 45 dB SPL. Hemoconcentration caused no apparent changes in the cochlear function in our animals. Although these findings may reflect species differences, hemoconcentration might still be a factor causing sudden hearing loss in older, atherosclerotic patients.

This study investigated the vascular effect of ferromagnetic obstruction of cochlear blood vessels in the guinea pig using dual-channel laser Doppler flowmetry. To improve this technique, we tested new types of magnets and iron spheres. In so doing, the cochlear temperature was lowered selectively and general hypothermia was avoided. The success of vascular impairment in the inner ear was found to depend on the experimental conditions used. Given normothermic conditions (38 degrees C body temperature), a clear reduction in cochlear blood flow (CBF) was found in only about 30% of the animals tested when an aluminium-nickel-cobalt alloy magnet and carbonyl iron spheres were used, while this ratio increased to about 80% under general hypothermia (33 degrees C). Using a stronger neodymium-iron-boron magnet and smaller-sized iron spheres, we found the success of vascular obstruction to be approximately 70% under normothermia and 100% with local hypothermia (to 33 degrees C) of the cochlea. Although the extent of vascular impairment revealed a considerable interindividual variation, the present findings demonstrate that ferromagnetic intervention in CBF with dual-channel laser Doppler flowmetry can be used to investigate the effect of quantified cochlear ischemia on inner ear physiology in the guinea pig model and test various therapeutic strategies.

Studies of the dynamic characteristics of cochlear blood flow (CBF) utilizing laser Doppler flowmetry (LDF) in laboratory animals have provided a new approach to the understanding of control mechanisms of CBF and the role of the CBF in cochlear disorders. However, few studies exist indicating that LDF of human CBF may be possible. Since bone thickness, density, structure characteristics, and blood flow all greatly affect LDF recording, we examined the anatomy of the human promontory for inter-individual variations in thickness, quality and vascularity of the bone and mucosa and recorded middle ear topographic relationships to the underlying cochlear lateral wall vasculature. Temporal bones from 21 cadavers without known premortem histories of ear disease were obtained. India ink was infused selectively via the vertebral or carotid system to study the origin of bone/ mucosa circulation to the otic capsule. Light microscopy revealed that the human promontory was characterized as cortical bone having few blood vessels. The thickness of the bone measured at four horizontal levels and mucosa at the top of promontory and anteriorly around the tympanic plexus varied from 1.67 +/- 0.64 to 1.13 +/- 0.26 mm for bone and 0.06-0.13 mm for mucosa. The thinnest bone was found around the tympanic plexus, where the bone thickness varied from 0.6 to 1.2 mm. Previous data indicate that current LDF instruments can provide a linear measure of blood flow through bone thicknesses of 1-3 mm or more (depending on the type of bone). Data from the current study indicate that direct valid dynamic measures of CBF are possible in humans. Since the optimal area available is small, the topography of the middle ear should be well known and the recording site well defined to obtain valid results.

To elucidate the etiology and pathogenesis of sudden hearing loss, the effect of experimental cochlear thrombosis on oxygenation and the auditory function of the inner ear was investigated in anesthetized guinea pigs. Impairment of cochlear blood flow (CBF) was induced by ferromagnetic obstruction of cochlear blood vessels at lowered body temperature. Perilymphatic oxygen partial pressure (PO2) in the basal scala tympani (about 200 microm below the round window membrane) was measured polarographically using micro-coaxial needle electrodes. Auditory function was examined by recording cochlear microphonic (CM) frequency responses, compound action potentials (CAP) and auditory evoked brainstem responses (ABR). Findings demonstrated a considerable decrease in the mean perilymphatic PO2 of 40%, 2 h after the start of the experiment. Mean CM and N1 CAP amplitudes were reduced by about 25% each and ABR by 18%. No significant changes were observed in the latencies of either CAP or ABR. Mean basal CBF was found to decrease by 35%, as measured by laser Doppler flowmetry in a parallel study. The present findings demonstrate that vascular impairment in the inner ear results in a considerable drop in intracochlear oxygenation, causing a significant loss in the auditory response.

To understand better the microcirculation in the inner ear in relation to blood viscosity, we examined the effects of pentoxifylline (PXF) and nitroprusside (NP) on cochlear blood flow (CBF) in healthy adult guinea pigs in relationship to various hematocrit (H1) values. There was no correlation between Ht value and the maximum decrease of mean blood pressure after PXF infusion, whereas there was a positive correlation between Ht and the maximum increase in CBF. No such relationship was found after NP infusion. A graph plot of each animal's blood oxygen transport capacity (i.e., Ht/blood viscosity) was found to have a convex form and to increase with a shift of the peak to a higher Ht area after PXF infusion. These findings indicate that a decrease in blood viscosity may improve CBF and increase oxygen transport capacity of blood.

The anionic sites on the basement membrane in the cochlea are believed to act as a charge barrier. Using polyethyleneimine (PEI) as a cationic tracer, we examined the effects of cisplatin (CDDP) on anionic sites in the basement membrane in the cochlea. Eight Hartley-strain guinea pigs were separated into control (buffer administration) and CDDP groups. Ultrathin sections of the basal and third turns of the cochlear ducts were examined using a transmission electron microscope. A marked decrease of PEI distribution was noted in the strial vessels of the CDDP group compared to the control group. However, the two groups showed no significant differences in PEI particles on the basement membranes in the basilar and Reissner's membranes, or in the basal and third turns. These findings suggest that the charge barrier in the stria vascularis may be easily injured by the administration of CDDP.

Ginkgo biloba extract (EGb 761) was administered orally for 4 or 6 weeks to healthy adult guinea pigs. Animals were then decapitated under deep ketamine anesthesia. Post-mortem morphometric measurements of cochlear vessels in the spiral lamina revealed a vasodilating effect of the extract in four of ten animals following 6 weeks of treatment. In vivo testing of the effect of 4 or 6 weeks of treatment with EGb 761 was monitored with laser Doppler flowmetry of the cochlear blood flow under pathological conditions. Results demonstrated that EGb 761 partly counteracted sodium salicylate-induced decreases in cochlear blood flow (CBF) and enhanced CBF increases induced by hypoxia. These findings indicate that EGb 761 may help to improve oxygenation in cochleas with compromised blood flow.

The effects of intravenous furosemide on the perilymphatic oxygen tension of the scala tympani (OT) in the guinea pig and the relationship between changes in OT and changes in auditory cortical-evoked responses were studied, as well as changes in cochlear morphology. Furosemide in dosages of 25 mg/kg and 50 mg/kg caused a sharp decline in OT in addition to elevation of the threshold of auditory cortical-evoked responses. Ischemia of the cochlear stria vascularis was also found but without any damage of hair cells at the light microscopic level. Changes in OT were associated with transient threshold elevations and ischemia of the stria vascularis. Improvements in hearing were directly proportional to the recovery of OT.

Autoregulation is the capacity of an organ system to maintain organ blood flow constant in response to changes in arterial blood pressure (BP). The current study was carried out to investigate the effect of age on autoregulation of cochlear blood flow (CBF) in mice. CBF was measured using a laser-Doppler flowmeter while BP was increased by angiotensin II injections and decreased by exsanguination in 2-month-old, 10-month-old and 18-month-old CBA mice. Autoregulation of CBF was significantly weaker in the 2-month-old mice when compared to the older mice. Although CBF autoregulation was weaker in the 18-month-old mice compared to the 10-month-old mice, this difference was not statistically significant. These results suggest that autoregulation changes with maturation and age. Findings are discussed in relationship to the possible development of presbycusis.

A photochemical reaction between intravenous rose bengal and xenon light was used to induce a selective thrombus in the rat anterior inferior cerebellar artery (AICA). Compound action potentials (CAPs) were recorded by electrocochleography and cochlear blood flow (CBF) was monitored by laser Doppler flowmetry. Photothrombotic occlusion of the AICA caused inner ear ischemia to various degrees with or without alterations of the CAP. With use of this model we investigated the critical range of the CBF for preserving cochlear function, represented by the CAPs induced with 8 kHz half-wave of sinusoid at 100 dB SPL. Results then showed that a CBF range between 26.7% and 42.9% of baseline was somewhat critical for maintenance of cochlear function in an acute phase of ischemia. Pretreatment with heparin significantly delayed thrombotic occlusion of the AICA in a dose-dependent manner. Further use of our model for inner ear ischemia may be useful for studying pathophysiology and pharmacological therapy of cochlear disturbances subsequent to circulatory disorders.

To determine the relationship between the dynamics of mean arterial blood pressure (MABP) elevation and possible changes in the cochlear microcirculation the cochlear blood flow (CBF) was measured in guinea pigs by a laser Doppler method. The MABP was elevated at rates ranging from 0.02 mmHg/s to 4 mmHg/s by intravenous infusions of norepinephrine or epinephrine in various concentrations. A fall in MABP was induced by exsanguination of the animals. The purpose of the experiments was to record the time of onset and course of an expected autoregulation in the cochlea in response to slow or rapid changes in MABP. The data suggest that there is no short-term autoregulation in the cochlear microcirculation reflecting the increase of the MABP, but a slight compensation occurs when the MABP declines. These latter changes could be attributed to the high CO2 sensitivity of the cochlear blood vessels.

We investigated the effects of increased cerebrospinal fluid (CSF) pressure on cochlear blood flow (CoBF) and cerebral blood flow (CBF) in guinea pigs. CoBF and CBF were recorded simultaneously using two laser-Doppler flowmeters, and blood flow volume in each part of the cochlea and the brain was measured by the non-radioactive microsphere method. CoBF was reduced by increased CSF pressure but the reduction was not persistent. Although inner ear pressure was elevated to the same level as CSF pressure, CoBF was not decreased by the pressure elevation as much as was CBF. Our results suggest that CoBF is relatively resistant to increases in CSF pressure.

This study examined the effects of acoustic exposure at different intensities on cochlear blood flow (CBF) using laser Doppler flowmetry. CBF was measured in anesthetized guinea pigs exposed to either a 10 kHz pure tone at 125, 105, or 90 dB SPL, or wide-band noise at 85 dB SPL for 1 h. Mean arterial blood pressure and heart rate were recorded continuously. Arterial acid-base status, cochlear temperature, cochlear microphonics (CM), and compound action potentials (CAP) were measured before and after exposure. There was a small, but significant, steady decline in basal CBF after 40 min loud sound exposure (125 dB SPL), but no change in basal CBF occurred with the lower intensities (85-105 dB SPL). In contrast, there was a significant increase in apical CBF after 1 h exposure to either moderate wideband noise (85 dB SPL) or a 10 kHz tone at 105 dB SPL. These changes persisted during a 20-min post-exposure period. In most cases, the cochlear temperature and cardiorespiratory variables monitored remained unchanged during and after the exposures as compared to the controls. CM and CAP amplitudes showed extensive losses after acoustic overstimulation (125 dB SPL), but no permanent changes were found at the lower intensities used. The present findings confirm the occurrence of intensity-related effects of acoustic exposure on the cochlear microcirculation.

The cochlear glomeruli were studied in guinea pigs using scanning electron microscopy of vascular corrosion casts and transmission electron microscopy of tissue sections. Two types of coiled vessels forming the cochlear glomeruli were found in the bony wall of the modiolus. First, upper glomeruli were seen situated in the bony wall next to the scala vestibuli; second, lower glomeruli were located in the osseous spiral lamina just above the spiral ganglion. Upper glomeruli gave rise to radiating arterioles which supplied capillaries of the stria the spiral lamina and limbus. Unlike the main supplying arteries, smooth muscle cells were not present in the walls of the arterioles forming the glomeruli and a peculiar layer of lamellar pericytes was found. The arterioles were strikingly longer than their parent vessels and no autonomic nerves were found in close spatial relationship. Hence, these findings indicate that the cochlear glomeruli serve as efficient devices for reducing cochlear blood pressure.

Changes in cochlear microcirculation and oxygenation and auditory function were examined in anesthetized guinea pigs during prolonged hypoxic ventilation (8% oxygen in nitrogen) for 1 h. Cochlear blood flow and perilymphatic oxygen partial pressure were measured using laser Doppler flowmetry and oxygen-sensitive microelectrodes. Auditory function was examined by recording cochlear microphonics, compound action potentials and auditory evoked brainstem response. Blood pressure and heart rate were monitored. During systemic hypoxia, the perilymphatic PO2 dropped on average to about 70% of the initial value. Cochlear and brainstem potentials showed a mean reduction to 75-82%. Different effects of hypoxia on cochlear blood flow were observed and included decreases as well as increases. Mean arterial blood pressure declined significantly during hypoxia, while the heart rate remained constant. The changed variables returned to normal during reventilation with room air. The findings are discussed with regard to their significance as an animal model for the study of hypoxia-induced cochlear pathophysiology.

The sensitivity of the cochlea is dependent upon maintenance of a delicate homeostatic environment. One mechanism which participates in providing this environment is the autoregulation of cochlear blood flow. This autoregulation is ensured through the interaction of sympathetic, peptidergic and hemodynamic mechanisms. The current study demonstrates an adaptation that also participates in cochlear blood flow autoregulation. Specifically, an anterior inferior cerebellar arterial network is described and the relative contributions of each of its vessels to total cochlear blood flow is measured using laser Doppler flowmetry. The results show that each collateral vessel contributes to the blood supply of the cochlea and that reperfusion is accompanied by hyperemia. These findings suggest an adaptation that provides stable blood flow through redundancy and compensatory potential. Additionally, these observations have implications for experimental models of ischemia.

The angioarchitecture of the guinea pig cochlea has been investigated closely using light microscopy and resin injections. However, detailed information concerning the vasculature of the modiolus is still unavailable, and even the existence of venous drainage through the internal auditory meatus is not agreed upon. In the present investigation, vascular casts of guinea pig temporal bones were studied using scanning electron microscopy. A vessel, formed by the confluence of the vascular network on the modiolar wall and having a spiral course into the internal auditory meatus was found in the modiolus of the basal turn. The vessel had a venous pattern on its cast surface and, after existing from the internal auditory meatus, drained finally into the dural sinus. These scanning electron microscopic findings were confirmable by serial sections of the dural veins in the internal auditory meatus and the modiolus. The vessel found may correspond to the so-called internal auditory vein, but it would be more appropriate to call it "the vein of the internal auditory meatus," since it appears to be an independent route of venous drainage from the modiolus.

The cochlear blood flow of healthy adult guinea pigs was measured with a laser Doppler flowmeter and flow dynamics were analyzed on the basis of autoregulation. Angiotensin II infusion was used to raise blood pressure, while phlebotomy was done to lower blood pressure. The characteristics of autoregulation of cerebral blood flow and muscular blood flow were also investigated. Cochlear blood flow was considered to have some autoregulation but was less than brain blood flow, which showed significant regulation. Muscular blood flow seemed to have no similar regulatory mechanism.

To clarify the characteristics of the blood circulation in the cochlea, we correlated cochlear blood flow and perilymphatic oxygen tension at various blood pressures. Cochlear blood flow was measured in guinea pigs by laser Doppler flowmetry, and perilymphatic oxygen tension by polarography. Blood pressure changes were induced by angiotensin II injection, trimetaphan camsylate injection and blood withdrawal. Cochlear blood flow generally paralleled systemic blood pressure, indicating a close correlation. In contrast, perilymphatic oxygen tension was slower to increase and decrease. However, when systemic blood pressure was lowered more gradually, perilymphatic oxygen tension did not show the same lag. These findings indicate that perilymphatic oxygen tension parallels systemic blood pressure when changes induced are slower and in a physiological range.

In order to test the applicability of laser-Doppler flowmetry in monitoring cochlear blood flow clinically, the thickness and the helium-neon laser light transmission of specimens of human, rat and guinea pig promontory bone and human skin were determined. Furthermore, comparative laser-Doppler measurements were taken from the promontory in patients, rats and guinea pigs. Due to the different thicknesses of the promontory bone in different species, the light transmission was found to be considerably higher for the animal cochlea (rat, 15%; guinea pig, 6.6%) than the human cochlea (1.7%). However, a clearly higher laser-Doppler signal was recorded from both the human and the rat cochleas as compared with the guinea pig. The relative laser light attenuation by the human skin specimens corresponded to that of the human promontory bone. The findings are discussed with regard to the suitability of the laser-Doppler method for blood flow measurements in the human cochlea.

In order to induce acute transient local blood flow impairment in the guinea pig cochlea, terminal vessels arising from the proximal and middle third of the basilar artery and from the rostral part of the collateral vertebral artery near their junction were occluded by temporary (1-2 min) compression. Clear identification of the anterior inferior cerebellar artery was impeded due to great variation in branching of the cerebellar arteries. To quantify the effect of the vascular occlusion on the cochlear microcirculation, laser Doppler flowmetry was used. Successive compression of the cerebellar arteries resulted in individually differentiated effects on the Doppler signal from the cochlea. In about half of the experiments there was a decrease in the laser signal to 25-55% of the initial level, while in the other cases no clear decrease occurred. Proximal obstruction of the basilar artery was found to reduce the cochlear blood flow up to 10-25% of its initial level, indicating that the Doppler signal primarily reflects microcirculation within the membranous cochlea. The findings are discussed with regard to their significance as an animal model for acute transient cochlear hypoxia.

For an accurate histological evaluation of cochlear blood flow, it is essential to fix the cochlear vessels while maintaining their physiological state. In the present study, we administered 10% CO2 to guinea pigs and then used phase-contrast microscopy to determine how two different methods of fixation influenced the cochlear vasculature. The first method of fixation employed perilymphatic perfusion in vivo, while the second one involved fixation after decapitation. Decapitation caused significant changes in the vessels of the stria vascularis, including constriction and sludging. In contrast, no sludging occurred in the perilymphatic perfusion method and erythrocyte morphology was preserved. However, dilatation of the strial blood vessels occurred after the inhalation of 10% CO2 even in the decapitation method. The results demonstrate that particular attention must be paid to the fixation method used, especially when evaluating the blood flow of the stria vascularis.

The effects of sudden occlusion of the vein of the cochlear aqueduct (VCAQ) on the cochlear blood flow, endocochlear potential (EP), endolymphatic and perilymphatic fluid pressures (PE and PP) were studied in the guinea pig. Cochlear blood flow showed a sudden decrease, and EP began to drop within 90 s, ranging from 50 to 70 mV in 5 of 11 animals studied, recovering to normal levels when the animals were placed on a continuous inhalation of carbogen. The PE and PP increased simultaneously (max. PE = 3.4 +/- 1.4 mm Hg; max. PP = 2.5 +/- 1.0 mm Hg) and returned to their initial values after 5 min. The EP was sustained within the normal range, even when there was an apparent decrease in cochlear blood flow (61.4 +/- 8.4%). We believe that variations in EP following VCAQ occlusion were due to anatomical differences in collateral venous communications among the animals studied. Carbogen inhalation produced uniform recovery patterns, indicating that individual collateral vessel responses were eliminated.

The laser Doppler flowmeter may give responses to loud sound that reflect the vibration of cochlear structures rather than changes in cochlear blood flow. The present study demonstrates that the positive artifactual response (i.e., increased flow reading) to sound at frequencies above approximately 5 kHz can be eliminated by using flowmeters which have electronic filters at 4 and 12 kHz, limiting the bandwidth of the optical Doppler shifted frequency range to lower frequencies. However, when using the 4 kHz filter a "residual" immediate negative response to loud high-frequency sound (10 kHz tone at 125 dB SPL) is evident at the beginning of the exposure. These findings are discussed with regard to the suitability of the method for investigating the effect of sound/noise on cochlear blood flow.