Changes 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.

Measurement of Strial Blood Flow in Mouse Cochlea Utilizing an Open Vessel-Window and Intravital Fluorescence Microscopy.

Transduction of sound is metabolically demanding, and the normal function of the microvasculature in the lateral wall is critical for maintaining endocochlear potential, ion transport, and fluid balance. Different forms of hearing disorders are reported to involve abnormal microcirculation in the cochlea. Investigation of how cochlear blood flow (CoBF) pathology affects hearing function is challenging due to the lack of feasible interrogation methods and the difficulty in accessing the inner ear. An open vessel-window in the lateral cochlear wall, combined with fluorescence intravital microscopy, has been used for studying CoBF changes in vivo, but mostly in guinea pig and only recently in the mouse. This paper and the associated video describe the open vessel-window method for visualizing blood flow in the mouse cochlea. Details include 1) preparation of the fluorescent-labeled blood cell suspension from mice; 2) construction of an open vessel-window for intravital microscopy in an anesthetized mouse, and 3) measurement of blood flow velocity and volume using an offline recording of the imaging. The method is presented in video format to show how to use the open window approach in mouse to investigate structural and functional changes in the cochlear microcirculation under normal and pathological conditions.

Lipopolysaccharide decreases cochlear blood flow dose dependently in a guinea pig animal model via TNF signaling.

To evaluate the effect of Lipopolysaccharide (LPS), a bacterial endotoxin on cochlear microcirculation, and its mode of action. Twenty-five Dunkin-Hartley guinea pigs were divided into five groups of five animals each. After surgical preparation, cochlear microcirculation was quantified by in vivo fluorescence microscopy. Placebo or LPS (1mg, 10µg, and 100ng) was applied topically, and microcirculation was measured before and twice after application. A fifth group was pretreated with etanercept, a tumor necrosis factor (TNF) antagonist, and afterward the lowest LPS concentrations that yielded significant results (10µg) were applied. In the groups that had been treated with 1mg and 10µg LPS, a significant drop in cochlear microcirculation was observed after 30 (.791±.089 Arbitrary Units (AU), compared to baseline, and .888±.071AU) and 60 (.756±.101 AU and .817±.124 AU, respectively) minutes. The groups that had been treated with 100ng LPS and that had been pretreated with etanercept showed no significant change in cochlear blood flow compared to placebo. Lipopolysaccharide shows a dose-dependent effect on cochlear microcirculation; this effect can already be observed after 30min. Pretreatment with etanercept can abrogate this effect, indicating that TNF mediates the effect of LPS on cochlear microcirculation.

Fingolimod (FTY-720) is Capable of Reversing Tumor Necrosis Factor Induced Decreases in Cochlear Blood Flow.

The potential of Fingolimod (FTY-720), a sphingosine-1-phosphate analogue, to revoke the changes in cochlear blood flow induced by tumor necrosis factor (TNF) was investigated. Impairment of cochlear blood flow has often been considered as the common final pathway of various inner ear pathologies. TNF, an ubiquitous cytokine, plays a major role in these pathologies, reducing cochlear blood flow via sphingosine-1-phosphate-signaling. Fifteen Dunkin-Hartley guinea pigs were randomly assigned to one of three groups (placebo/placebo, TNF/placebo, TNF/FTY-720). Cochlear microcirculation was quantified over 60 minutes by in vivo fluorescence microscopy before and after topical application of placebo or TNF (5 ng/ml) and after subsequent application of placebo or FTY-720 (200 μg/ml). Treatment with TNF led to a significant decrease of cochlear blood flow.Following this, application of placebo caused no significant changes while application of FTY-720 caused a significant rise in cochlear blood flow. FTY-720 is capable of reversing changes in cochlear blood flow induced by application of TNF. This makes FTY-720 a valid candidate for potential treatment of numerous inner ear pathologies.

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.

Effects of perilymphatic pressure, sodium nitroprusside, and bupivacaine on cochlear fluid pH of guinea pigs

Conclusions: Hydrostatic positive pressure and vasoconstrictor acidified the cochlear fluids, whereas the vasodilator made the fluids alkaline. CBF might play a role in regulating cochlea fluid pH. Objectives: Cochlea fluid pH is highly dependent on the HCO3−/CO2 buffer system. Cochlear blood flow (CBF) supplies O2 and removes CO2. It is speculated that cochlear blood flow changes might affect the balance of the HCO3−/CO2 buffer system in the cochlea. It is known that the elevation of inner ear pressure decreases the CBF, and local application of vasodilating or vasoconstricting agents directly to the cochlea changes the CBF. The purpose of this study was to elucidate the effect of positive hydrostatic inner ear pressure and application of a vasodilator and vasoconstrictor of cochlear vessels on the pH of the endolymph and perilymph. Methods: The authors performed animal physiological experiments on 30 guinea pigs. Hydrostatic positive pressure was infused through a glass capillary tube inserted into the scala tympani of the basal turn. The vasodilator, nitric oxide donor (sodium nitroprusside; SNP), and the vasoconstrictor, bupivacaine, were placed topically onto the round window of the guinea pig cochlea. Endolymph pH (pHe) and endocochlear potential (EP) were monitored by double-barreled ion-selective microelectrodes in the second turn of the guinea pig cochlea. During the topical application study, scala vestibuli perilymph pH (pHv) was also measured simultaneously in the second turn. Results: The application of hydrostatic positive pressure caused a decrease in pHe and EP. Positive perilymphatic pressure caused the endolymph to become acidic pressure-dependently. Application of 3.0% SNP evoked an increase in both the pHe and pHv, following by a gradual recovery to baseline levels. On the other hand, 0.5% bupivacaine caused a decrease in both the pHe and pHv. The EP during topical application showed slight, non-significant changes.

Histaminergic H3-Heteroreceptors as a Potential Mediator of Betahistine-Induced Increase in Cochlear Blood Flow

Objective: Betahistine is a histamine-like drug that is considered beneficial in Ménière's disease by increasing cochlear blood flow. Acting as an agonist at the histamine H₁-receptor and as an inverse agonist at the H₃-receptor, these receptors as well as the adrenergic α₂-receptor were investigated for betahistine effects on cochlear blood flow. Materials and Methods: A total of 54 Dunkin-Hartley guinea pigs were randomly assigned to one of nine groups treated with a selection of H₁-, H₃- or α₂-selective agonists and antagonists together with betahistine. Cochlear blood flow and mean arterial pressure were recorded for 3 min before and 15 min after infusion. Results: Blockage of the H₃- or α₂-receptors caused a suppression of betahistine-mediated typical changes in cochlear blood flow or blood pressure. Activation of H₃-receptors caused a drop in cochlear blood flow and blood pressure. H₁-receptors showed no involvement in betahistine-mediated changes of cochlear blood flow. Conclusion: Betahistine most likely affects cochlear blood flow through histaminergic H₃-heteroreceptors.

Thin and open vessel windows for intra-vital fluorescence imaging of murine cochlear blood flow

Normal microvessel structure and function in the cochlea is essential for maintaining the ionic and metabolic homeostasis required for hearing function. Abnormal cochlear microcirculation has long been considered an etiologic factor in hearing disorders. A better understanding of cochlear blood flow (CoBF) will enable more effective amelioration of hearing disorders that result from aberrant blood flow. However, establishing the direct relationship between CoBF and other cellular events in the lateral wall and response to physio-pathological stress remains a challenge due to the lack of feasible interrogation methods and difficulty in accessing the inner ear. Here we report on new methods for studying the CoBF in a mouse model using a thin or open vessel-window in combination with fluorescence intra-vital microscopy (IVM). An open vessel-window enables investigation of vascular cell biology and blood flow permeability, including pericyte (PC) contractility, bone marrow cell migration, and endothelial barrier leakage, in wild type and fluorescent protein-labeled transgenic mouse models with high spatial and temporal resolution. Alternatively, the thin vessel-window method minimizes disruption of the homeostatic balance in the lateral wall and enables study CoBF under relatively intact physiological conditions. A thin vessel-window method can also be used for time-based studies of physiological and pathological processes. Although the small size of the mouse cochlea makes surgery difficult, the methods are sufficiently developed for studying the structural and functional changes in CoBF under normal and pathological conditions.

Changes in cochlear blood flow in mice due to loud sound exposure measured with Doppler optical microangiography and laser Doppler flowmetry.

In this work we determined the contributions of loud sound exposure (LSE) on cochlear blood flow (CoBF) in an in vivo anesthetized mouse model. A broadband noise system (20 kHz bandwidth) with an intensity of 119 dB SPL, was used for a period of one hour to produce a loud sound stimulus. Two techniques were used to study the changes in blood flow, a Doppler optical microangiography (DOMAG) system; which can measure the blood flow within individual cochlear vessels, and a laser Doppler flowmetry (LDF) system; which averages the blood flow within a volume (a hemisphere of ~1.5 mm radius) of tissue. Both systems determined that the blood flow within the cochlea is reduced due to the LSE stimulation.

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.

Monitoring hypoxia induced changes in cochlear blood flow and hemoglobin concentration using a combined dual-wavelength laser speckle contrast imaging and Doppler optical microangiography system.

A synchronized dual-wavelength laser speckle contrast imaging (DWLSCI) system and a Doppler optical microangiography (DOMAG) system was developed to determine several ischemic parameters in the cochlea due to a systemic hypoxic challenge. DWLSCI can obtain two-dimensional data, and was used to determine the relative changes in cochlear blood flow, and change in the concentrations of oxyhemoglobin (HbO), deoxyhemoglobin (Hb) and total hemoglobin (HbT) in mice. DOMAG can obtain three-dimensional data, and was used to determine the changes in cochlear blood flow with single vessel resolution. It was demonstrated that during a hypoxic challenge there was an increase in the concentrations of Hb, a decrease in the concentrations of HbO and cochlear blood flow, and a slight decrease in the concentration of HbT. Also, the rate of change in the concentrations of Hb and HbO was quantified during and after the hypoxic challenge. The ability to simultaneously measure these ischemic parameters with high spatio-temporal resolution will allow the detailed quantitative analysis of several hearing disorders, and will be useful for diagnosing and developing treatments.

Effects of hypoxia on cochlear blood flow in mice evaluated using Doppler optical microangiography

Reduced cochlear blood flow (CoBF) is a main contributor to hearing loss. Studying CoBF has remained a challenge due to the lack of available tools. Doppler optical microangiography (DOMAG), a method to quantify single-vessel absolute blood flow, and laser Doppler flowmetry (LDF), a method for measuring the relative blood flow within a large volume of tissue, were used for determining the changes in CoBF due to systemic hypoxia in mice. DOMAG determined the change in blood flow in the apical turn (AT) with single-vessel resolution, while LDF averaged the change in the blood flow within a large volume of the cochlea (hemisphere with ∼1 to 1.5 mm radius). Hypoxia was induced by decreasing the concentration of oxygen-inspired gas, so that the oxygen saturation was reduced from >95% to ∼80%. DOMAG determined that during hypoxia the blood flow in two areas of the AT near and far from the helicotrema were increased and decreased, respectively. The LDF detected a decrease in blood flow within a larger volume of the cochlea (several turns averaged together). Therefore, the use of DOMAG as a tool for studying cochlear blood flow due to its ability to determine absolute flow values with single-vessel resolution was proposed.

Disturbances of Auditory Function during Vestibular Schwannoma Surgery: Insights from Intraoperative Distortion-Product Otoacoustic Emissions

Introduction: Hearing preservation in patients operated on for a vestibular schwannoma is of growing concern. The goal of this work was to monitor auditory function online using distortion-product otoacoustic emissions (DPOAEs) to sort out the different issues leading to postoperative sensorineural hearing loss, knowing that DPOAEs are extremely sensitive to cochlear blood flow changes.

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.

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.

A comparative study of intratympanic steroid and NO synthase inhibitor for treatment of cochlear lateral wall damage due to acute otitis media

We studied the damage to the cochlear lateral wall induced by otitis media and the therapeutic effects of intratympanic administration of steroid and nitric oxide (NO) synthase inhibitor. In Sprague–Dawley rats, right middle ear cavities were inoculated with lipopolysaccharide, followed after 30 min by intratympanic administration of dexamethasone, NOS-inhibitor or PBS. Twenty-four hours after lipopolysaccharide inoculation, cochlear blood flow was measured by laser-Doppler flowmetry. Prostaglandin E 1 was topically applied to the round window membrane of the right ear and changes in cochlear blood flow were calculated. Changes of cochlear blood flow were significantly different among the three groups. Increases in cochlear blood flow following PGE 1 application were higher in the group that received NOS-inhibitor. Electron microscopic examination revealed that changes in the stria vascularis were less severe in rats treated with dexamethasone or NOS-inhibitor. Our results show the effectiveness of intratympanic dexamethasone or NOS-inhibitor in treating cochlear lateral wall damage caused by otitis media.

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 nitric oxide synthase inhibitor on cochlear blood flow

We observed in rats the changes in cochlear blood flow (CoBF) and cutaneous blood flow of the abdominal wall (AbBF) after the administration of the NO synthase inhibitor, N-nitro- L-arginine-methyl ester (L-NAME). Ten minutes after i.v. infusion of L-NAME (0.2, 1, 5, 10 mg/kg), L-arginine, which is a substrate of NO, was infused (100 mg/kg) i.v. Employing a laser Doppler flowmeter, the changes in blood flow were recorded from the basal turn of the right cochlea or the abdominal wall and blood pressure (BP) was recorded from the left femoral artery simultaneously. Vascular conductance (VC) was calculated from CoBF/mean BP (cochlear VC) or AbBF/mean BP (abdominal VC). The findings in rats generally agreed with those in guinea pigs [Brechtelsbauer et al., Hear. Res. 77 (1994) 38–42]. Intravenous infusion of L-NAME produced a dose-dependent depression of cochlear VC at 0.2 mg/kg (−18.9), 1 mg/kg (−37.9%), 5 mg/kg (−45.8%) and 10 mg/kg (−48.3%). AbBF also decreased after infusion of L-NAME (5 mg/kg) but to a lesser degree (−41.1% in VC) with no significance compared to CoBF (5 mg/kg). Infusion of L-arginine partially reversed the CoBF decrease caused by L-NAME. The group of 0.2 mg/kg infusion of L-NAME showed the largest degree of recovery with L-arginine, while the 10 mg/kg group showed the smallest. The decrease in AbBF did not recover substantially with L-arginine, the degree being less than that of each group in the CoBF experiment. It was suggested that the NO/soluble guanylate cyclase/cGMP system is more active in the cochlear microcirculation. With the round window (RW) application of 1% L-NAME (2 μl), cochlear VC was decreased by 21.6%, which was closest to that of the 0.2 mg/kg group of L-NAME i.v. infusion. The cochlear VC depression after local application of L-NAME did not show any recovery (−0.3%) by RW application of 5% L-arginine (2 μl) 25 min after L-NAME application; a slight gradual increase was observed when a higher concentration (20%) of L-arginine was applied to the RW. We propose that i.v. infusions of L-NAME and L-arginine primarily affect the precapillary arteriole of the spiral modiolar artery which effectively regulates microcirculation as a resistance vessel, and that RW application affects the vessels of the lateral wall, not the spiral modiolar artery because of the difficulty of substance diffusion.

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.

Laser Doppler Measurement of Cochlear Blood Flow Changes During Conditioning Noise Exposure

Laser Doppler Measurement of Cochlear Blood Flow Changes During Conditioning Noise Exposure