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Biomedical subjects

A L Nuttall

Publications and source records attributed to A L Nuttall.

At least 55 records · Page 3Linked to original sources

The mechanism and site of action of lidocaine hydrochloride in guinea pig inner ear.

Lidocaine was applied to the round window (RW) in order to localize its site of action in the cochlea. Cochlear microphonic (CM), summating potential (SP), and compound action potential (CAP) input/output functions were measured to a 16 kHz tone burst to assess the functional changes of the cochlea. In separate experiments, the effect of lidocaine on the whole cell current of isolated outer hair cells (OHC) was studied. A dose of 2 microliters of 40 mM lidocaine in saline solution, when applied to the RW, caused a small change in all measured variables, indicating a passage of the drug through the RW membrane to sites of action. However, 160 mM of lidocaine further decreased CM, SP, and CAP by a total of 40% from the control. A partial recovery occurred for CM during the 30 min follow-up period. CAP and SP continued to decline. In isolated OHCs, lidocaine decreased the whole cell current in a dose-dependent fashion. The KD for lidocaine effect on OHCs was 7 mM. Our in vivo results indicate that lidocaine affects OHCs and reduces CM, causing a subsequent reduction in SP and CAP. The increased effect of lidocaine on CAP and SP, while CM is recovering, suggests an additional specific effect of lidocaine on the cochlear nerve and/or on inner hair cells. Considering that lidocaine alters OHC current (in isolated hair cells) and that lidocaine does not affect endocochlear potential [Laurikainen et al. Acta Otolaryngol (Stockh) 1991: 112: 800-9], the observed CM changes are most likely due to an in vivo effect on OHCs. Thus, the early effect of lidocaine on the cochlea appears to be due to a significant change in organ of Corti function, rather than to direct anesthesia of the cochlear nerve. Later, an independent effect of the drug may occur on neural tissues in the inner ear.

Animals↗

Non-specific effect of beettahistine on cochlear electrophysiology in guinea pig.

Beettahistine hydrochloride (BH) is reported to be beneficial in the treatment of certain type of vestibulo-cochlear disorders. Experimentally is shown that BH inhibits vestibular firing rate and improves cochlear blood flow by dilatating the larger feeding vessels. Both these effects are weak, and hardly can explain the clinical benefits reported for the drug. We investigated the effect of BH on the organ of Corti electrophysiology in vivo. Two microliters of 1, 2, 5 and 10% saline solutions of BH was applied (in increasing order) to the round window (RW) membrane in an anesthetized guinea pig (n = 5). Summating potential (SP), action potential (AP), and cochlear microphonics (CM) were recorded at 16 kHz frequency using RW Ag wire electrode. The repeated applications of BH with increasing concentrations produced a dose-dependent threshold shift in CAP. The I/O function for 20, 30, 40, 50, 60, 70, and 80 dB at 16 kHz indicated that there was a saturation before complete blockade of the responsiveness in all measured parameters. SP and CM changes nearly followed CAP changes. The changes recover during 2 hours follow-up period. Our findings indicate that BH affects the organ of Corti electrophysiology. That the drug effect saturates before a complete blockade suggests non-specific effect of BH on the organ of Corti structures and cochlear nerve.

Animals↗

[Research on basilar membrane vibration of guinea pigs elicited by direct current pulse].

To investigate the electromotility of basilar membrane (BM) of guinea pigs in vivo, a couple of Platinum-iridium wire electrodes were placed into holes drilled in the scala vestibuli and scala tympani on the basal turn of cochlea separately. The organ of Corti was stimulated with rectangular direct current pulses. The displacement and velocity of BM were measured with Laser Doppler velocimeter. The results indicated that the displacement of BM elicited by current moved toward the scala where positive current was injected. The waveform of BM displacement was corresponding to the rectangular pulse of electric current step. Ringing responses could be seen at the onset and offset of current pulse that was the transient responses of outer hair cells. The frequency of the ringing was the same as that of characteristic frequency of partition in BM. It is supposed that the ringing of BM is an active process of depletive energy and participate with cochlear amplifier. In the insensitive cochlea or dead animal, direct current can still elicit a BM displacement but the ringing response is decreased or disappeared. This phenomenon is probably because of metabolic disturbance in damaged outer hair cells. The BM vibration induced by direct current is similar to that of induced by acoustic stimulation, which can transfer to other partition of BM by traveling wave. This characteristic has laid a foundation of electromotile hearing and electrically evoked otoacoustic emission.

Animals↗

Electrically evoked cubic distortion product otoacoustic emissions from gerbil cochlea.

It has been demonstrated that electrical stimulation of the cochlear partition results in basilar membrane vibration and otoacoustic emissions. Electromotility of stimulated outer hair cells (OHCs) elicits the electrically evoked otoacoustic emissions (EEOAEs). Although electrically evoked upper and lower sideband distortion products (DPs) have been reported, electrically evoked cubic DP has not been investigated. Since the acoustically evoked cubic DP is the most commonly used otoacoustic measure of cochlear nonlinearity, this study tested whether electrical stimuli evoke a cubic DP otoacoustic emission. An electrical current containing the frequency component f1 and f2 (f1 < f2) was delivered to the round window niche of the gerbil, and electrically induced sound pressure change in the external ear canal was measured with a microphone. It was found that, in addition to f1 and f2 EEOAEs, cubic DP (2f1-f2) and other emissions at 3f1-2f2, 2f2-f1 and f2-f1 frequencies are electrically evoked. The electrically evoked cubic DP growth is similar to that of an acoustically evoked cubic DP. An electrical stimulus at f1 or f2 and an acoustic stimulus at f2 or f1 produce an identical cubic DP to that evoked by two electrical stimuli and/or two acoustic stimuli at f1 and f2 frequencies. An acoustic suppressor at a frequency near f2 can completely suppress an electrically evoked cubic DP emission. These data demonstrate that DPs can be provoked by a complex two frequency electrical current delivered to the round window niche. These stimuli elicit mechanical vibrations, from stimulated OHCs near the round window, which propagate apically toward their characteristic frequency places on the basilar membrane, and produce combination DPs. Electrically evoked cubic DPs appear to be produced by the same nonlinear mechanism that generates acoustically evoked DPs.

Acoustic Stimulation↗

Electrophysiological and morphological evaluation of the acute ototoxicity of sodium nitroprusside.

Nitric oxide (NO) is a messenger molecule that mediates several physiological functions and pathological processes. Sodium nitroprusside (SNP), a potent vasodilator, when given clinically as an anti-hypertension agent, exerts its function by releasing NO. It was reported recently that SNP causes a loss of auditory nerve compound action potential (CAP) after topical application of SNP on guinea pig round window membrane (RWM). The current study was designed to investigate the ototoxic target of SNP through both electrophysiological and morphological approaches. The CAP threshold at frequencies ranging from 2 to 36 kHz, the cochlear microphonic quadratic distortion product (cmQDP, F2-F1, where F1 = 17.1 kHz; F2 = 18 kHz), and the cochlear microphonic (CM) at the frequency of F1 were recorded via a round window electrode before and up to 2 h after RWM application of 1 microliter of drug solution. Cochlear blood flow (CBF) and arterial blood pressure were monitored. The cochleae were then processed for morphological examination. The effect of SNP on endocochlear potential (EP) was also studied. Results showed that cmQDP, CM, and CAP, as well as EP, were suppressed in varying amounts, while CBF was substantially increased following drug application. Morphological evaluations showed swelling of the afferent inner radial dendrites within the basal cochlear turn in the higher concentration groups of SNP, while the hair cells presented no evidence of damage at the light microscopic level. The results indicate that SNP has an acute ototoxic effect in a concentration- and time-dependent manner. The targets of SNP ototoxicity are at least the afferent dendrites and stria vascularis.

Action Potentials↗

Nitric oxide mediates capsaicin-induced increase in cochlear blood flow.

Capsaicin has been previously shown to increase cochlear blood flow (CBF) in a dose-dependent manner. The aim of this study was to define the role of nitric oxide (NO) in capsaicin-induced changes in CBF. This was investigated in the anesthetized guinea pig, utilizing laser Doppler flowmetry. Application of capsaicin (64.8 and 6.48 nmol in 2 microliters of saline) to the round window membrane (RWM) caused increases in CBF (34 +/- 2.8% of baseline (BL) and 28 +/- 2.3% BL, respectively (P < 0.001)). Application of the NO synthase inhibitor, NG-nitro-L-arginine methyl ester (L-NAME) (10 mg/kg intravenously or topically to the RWM) reduced blood flow in the cochlea, as previously reported. After pretreatment with i.v. L-NAME, the effect of capsaicin on CBF was significantly decreased. With the dose of capsaicin at 64.8 nmol, the increase in CBF fell from 34 +/- 2.8% BL to 6.9 +/- 1.5% BL (P < 0.001), and at 6.48 nmol it fell from 28 +/- 2.3% BL to 4.8 +/- 1.6% BL (P < 0.001). RWM L-NAME application also decreased the capsaicin vasodilatation effect. A capsaicin dose of 64.8 nmol resulted in only a 10 +/- 2.5% BL increase in CBF, and with 6.48 nmol capsaicin the increase was 7.8 +/- 2.2% of BL (P < 0.001). Capsaicin-sensitive sensory neurons in other systems are generally known to release substance P (SP), which in turn elicits release of endothelium derived relaxing factor (NO). The results of this study indicate that NO is a mediator of capsaicin-sensitive sensory neuronal function in CBF regulation.

Animals↗

Steady-state sinusoidal velocity responses of the basilar membrane in guinea pig.

This report provides a detailed analysis of tone-evoked velocity responses of basilar membrane (BM) motion measured in the basal turn of the guinea pig cochlea. A laser Doppler vibrometer, coupled to a compound microscope, measured the velocity of reflective microbeads placed onto the scala tympani surface of the BM. The velocity responses of the stapes footplate were also determined, allowing the calculation of a BM transfer function. The normal transfer function is compared to that seen with cochlear "insensitivity" and postmortem. This comparison results in measures of the active process contribution to the magnitude and phase of the BM transfer function. It was found that the active process contributed as much as 65 dB of "gain" and 270 degrees of phase lag at the best frequency. Other details about features of input/output velocity functions and the derived mechanical frequency-tuning curve at a criterion of 50 micron/s are analyzed.

Acoustics↗

Relative blood velocity measurement in individual microvessels using the self-mixing effect in a fiber-coupled helium-neon laser.

A system has been developed for the measurement of relative blood velocity in micro-vessels by using the self-mixing effect of a laser. A helium-neon laser was coupled to a single-mode optical fiber and the pulled fiber tip (approximately 30 microns diameter) was positioned on a single microvessel. The backscattered Doppler-shifted laser light from moving red blood cells enters the laser cavity and modulates the laser output by influencing internal laser parameters. The signal of the laser output intensity change was produced using a fiber-coupled photodiode and processed by a signal processor. This processor yields an output signal proportional to the first moment of the power spectral density, i.e., the mean frequency of the Doppler shift, corresponding to the blood flow velocity on an arbitrary instrument scale. Results of the in vitro experiment demonstrated that the current method can detect moving particles in fluid and moving red blood cells in a small plastic tube. Data from the in vivo study showed that this system is capable of measuring relative blood velocity in arterioles and venules and can easily follow the cardiac cycle up to 360 beats/min. Primary data suggest that, in addition to high sensitivity, good spatial and temporal resolution, and convenience of use, the self-mixing technique may have an even greater capacity for analysis of blood flow in microvessels than explored in this study, since information on the absolute velocity and velocity distribution of red blood cells is available in self-mixing signal. Further study on its hematocrit dependence and particle bias effect is needed.

Animals↗

Autoregulation of cochlear blood flow in young and aged mice.

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.

Age Factors↗

Monoclonal antibody induced hearing loss.

Monoclonal antibodies KHRI-3 and KHRI-5 identify antigens expressed on inner ear supporting cells and auditory hair cells respectively. To determine if these antibodies affect inner ear function groups of syngeneic Balb/c mice were inoculated with hybridomas KHRI-3, KHRI-5 and other Ig-secreting hybridomas. Hybridomas UM-A9, UM-7F11, the non-secreting SP2/0 myeloma and mice with no hybridoma were used as controls. Animals were tested for auditory brainstem responses (ABR) for frequencies of 4, 8, 16 and 24 kHz, before the inoculation of the hybridomas and at intervals of 6 to 10 days thereafter or daily once tumors became palpable. In normal mice there were no changes in ABR thresholds over the course of the experiment. Other control animals showed little change in ABR even when the growth of the hybridoma or myeloma tumors were far advanced. Of the KHRI-5 hybridoma bearing animals only one of seven animals exhibited threshold shifts greater than 15 dB. In contrast, most mice bearing the KHRI-3 hybridoma exhibited high frequency threshold shifts of 40-50 dB that coincided temporally with the growth of the hybridoma, the presence of circulating KHRI-3 antibody, and greatly increased immunoglobulin titers. Ears from KHRI-3-bearing mice that developed high frequency hearing loss also had a novel type of lesion in the basal turn of the cochlea that was characterized by loss of outer hair cells and absence of typical supporting cell scars. Such changes were not found in control hybridoma-bearing mice. These findings suggest that KHRI-3 antibody has an effect on hearing that is secondary to damage to the organ of Corti and loss of outer hair cells. Our results have important implications for antibody-mediated mechanisms of hearing loss and provide an animal model in which to study this phenomenon.

Acoustic Stimulation↗

Age-related changes in cochlear vascular conductance in mice.

Vascular changes contribute to age-related hearing loss but the mechanisms involved in microvascular reactivity, particularly in the aged ear, are still incompletely understood. In this study, possible age-related changes in cochlear blood flow (CBF) and vascular reactivity were studied in presbycusic mice (C57BL/6) and young, age-matched, and old controls (CBA/J) without presbycusis. Reactivity was monitored by laser Doppler flowmetry and assessed by change in cochlear vascular conductance (VC) (defined as the ratio of CBF to blood pressure) in response to round window-applied sodium nitroprusside, a vasodilating agent. Mean VC response of C57BL/6 mice differed from controls both in maximum response and in post-drug recovery time. In C57BL/6 mice, mean VC increased about 28%, in contrast to an increase of over 40% in young and age-matched CBA/J controls. A less elevated VC response, similar to that of the presbycusic mice, was shown by aged (20-21 month) controls. Also, VC response in C57BL/6 mice was sustained throughout the 60 min observation period, while response of most CBA/J controls recovered in 50 min or less. These changes suggest age-dependent, pathologically-related altered responsiveness in cochlear vascular reactivity.

Aging↗

Dihydropyridines and verapamil inhibit voltage-dependent K+ current in isolated outer hair cells of the guinea pig.

Dihydropyridines and verapamil are widely used as blockers of voltage-dependent Ca++ channels. In this work we show that these compounds can have a direct blocking action on a class of voltage-activated potassium channels. Voltage-dependent whole-cell currents were recorded from isolated guinea-pig outer hair cells (OHCs) under conditions such that the free Ca++ concentration in both the internal and external solutions was minimized. A substantial Ca(++)-independent K+ current was revealed by this procedure. Both conventional K+ and Ca++ channel ligands inhibited this current. The order of potency (in terms of the half inhibitory concentrations (IC50) of channel inhibitors) was: nimodipine (6 microM) > Bay K 8644 (8 microM) > verapamil (11 microM) > 4-aminopyridine (22 microM) > nifedipine (32 microM) > quinine (49 microM) > TEA (10236 microM). Except for verapamil, these channel ligands reduced the size of the K+ currents without much alteration of the time course of the currents. In contrast, verapamil caused a more than 10-fold increase in the apparent inactivation rate of the K+ currents without significantly altering the activation of the currents. The observation that relatively low concentrations of calcium channel ligands can directly inhibit potassium currents in isolated OHCs indicates that caution should be taken when these pharmacological agents are used as tools for studying cochlear hair cell physiology.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗

Capsaicin-induced release of substance P increases cochlear blood flow in the guinea pig.

Physiological evidence from several studies suggests that endogenous vasoactive peptides, such as substance P (SP), and their respective receptor populations may participate in the mechanisms that govern the autoregulatory capacity of the cochlear vascular system. However, these studies do not provide evidence regarding the origin or mechanism of action of SP. Capsaicin sensitivity has been used as a marker for sensory neurons, and the release of SP following capsaicin treatment suggests a sensory transmitter role for SP. The present investigation examines the relationship between the capsaicin-sensitive sensory neurons and SP in the regulation of cochlear blood flow (CBF). In 75 pigmented guinea pigs, the cochlea was surgically exposed and a laser Doppler flowmeter probe placed on the bony surface of the first turn to monitor CBF. Capsaicin solutions (2 microliters, 0.01%, 0.001% and 0.0001%) applied to the round-window membrane (RWM) resulted in a dose-related CBF increase, without change in the systemic blood pressure. This effect could be inhibited by application of a specific SP receptor antagonist, [D-Pro2,D-Trp7,9]-SP, after which none of the capsaicin concentrations used induced a change in CBF. Moreover, after RWM application of 50 nmol/2 microliters of SP there was a significant increase in CBF. No CBF change was observed with the lower concentrations of 10 nmol SP or 100 pmol SP. These results indicate a role of SP in CBF regulation and give indirect evidence that SP is released from capsaicin-sensitive primary sensory neurons.

Animals↗

Autoregulation of cochlear blood flow in the hydropic guinea pig.

Previous data suggest that regulation of cochlear blood flow (CBF) may be abnormal in the hydropic guinea pig. The purpose of this study was to employ the technique of anterior inferior cerebellar artery (AICA) occlusion to measure CBF autoregulation in experimental endolymphatic hydrops. This study also addresses the role of the cochlear sympathetic neural innervation and nitric oxide in CBF regulation with hydrops. In anesthetized guinea pigs, CBF was measured with a laser Doppler flowmeter probe while the AICA was intermittently occluded with a microvascular occluder. The CBF response was measured in normal, 6-week, and 12-week chronically hydropic animals. The gain factors (0 = no autoregulation, 1 = complete autoregulation) for 1-min occlusion were 0.95 +/- 0.16 (control), 0.77 +/- 0.28 (6 week, P = 0.164), and 0.67 +/- 0.25 (12 week, P = 0.037). NG-nitro-L-arginine methyl ester (L-NAME), a competitive inhibitor of nitric oxide synthase, was infused intravenously to assess basal nitric oxide (an endogenous vasodilator) production in the hydropic ear. With infusion of L-NAME, CBF was reduced by 9.16 +/- 11%, 10.7 +/- 10% (P = 0.87), and 16.6 +/- 18% (P = 0.95), in the control, 6-week, and 12-week animals, respectively. In a separate group of 12-week hydropic animals, the left superior cervical ganglion (SCG) was anesthetized with lidocaine, and AICA occlusions were performed pre- and post-blockade. Prior to blocking the SCG, the gain was 0.712 +/- 0.02 and afterwards 0.708 +/- 0.051 (P = 0.93). The above results show that there was a statistically significant reduction in CBF autoregulation in the 12-week hydropic animals. There was no difference in basal nitric oxide production in normal versus hydropic animals nor was there a change in autoregulation following blockade of the SCG. These data provide clear evidence for reduced CBF autoregulation in experimental endolymphatic hydrops.

Animals↗

A reversible ischemia model in gerbil cochlea.

A completely reversible cochlear-ischemia animal model was developed, and an initial study of ischemia/reperfusion-induced cochlear function change is presented. The bulla of the anesthetized gerbil was opened through a ventral approach and the anterior inferior cerebellar artery and its branches were exposed. Cochlear blood flow (CBF) from the basal turn of the cochlea was monitored with a laser Doppler flowmeter. An electrically isolated microclamp was used to occlude the labyrinthine artery (LA). During LA clamping, the cubic distortion product (DP) was continuously recorded. The LA was repeatedly clamped for different durations in all animals, and CBF consistently showed full recovery after clamp release. No obvious change in vessel diameter or flow pattern was observed under a stereomicroscope. Mean blood pressure did not show significant change during clamping. Immediately upon LA clamping, CBF decreased rapidly nearly to zero. After clamp release, CBF demonstrated an immediate rapid increase, followed by a secondary gradual recovery to baseline. CBF recovery patterns were clamp duration-related. Within a few seconds of occlusion, DP decreased and reached a minimum of approximately 24% of the initial level in less that 30 s. Following reperfusion of the cochlea, DP gradually increased, decreased again, then slowly recovered. Time delay between CBF reperfusion and the first increase of DP was proportional to clamping duration, and the increased amplitudes demonstrated a negative relationship to clamp duration. We assume that the first decrease in DP during clamping was caused by ischemia in the cochlea; the second decrease, during the cochlear reperfusion, could be a form of reperfusion-induced change in cochlear function. This ischemia/reperfusion model in gerbil cochlea demonstrates excellent repeatability and reversibility. Since DP and other measurements can be used to dynamically monitor cochlear or hair cell functions, this model is useful in studies of auditory physiology and pathophysiology.

Animals↗

Electromotile hearing: evidence from basilar membrane motion and otoacoustic emissions.

Electrical stimulation of the cochlea is known to cause auditory sensations in humans and other animals. It also has been shown to produce emissions of sound from the inner ear. In the current study we investigate the relationship between electrically induced motion of the basilar membrane (BM) and the production of otoacoustic emissions. We test the hypothesis that electrical current-induced movements of the outer hair cell (OHC electromotility) result in intracochlear acoustic pressure which causes traveling waves on the BM. Our results demonstrate that the dominant response of the guinea pig inner ear to electric stimulation, at the round window membrane (RW) or across the cochlear duct, is a mechanical response of the organ of Corti. We observed that electrical stimulation of the cochlea produced traveling wave activity on the BM, measured with a laser Doppler velocimeter. The BM motion was accompanied by sound emitted by the cochlea for frequencies up to at least 25 kHz. Furthermore, bipolar rectangular current stimulation produced steady, bipolar displacements of the BM (to 2 nm), indicating functional elongation or contraction of OHCs occurs depending on the polarity of the current pulse. All of the evoked responses were absent after drug treatments eliminated the OHCs. Our data indicate that OHCs undergo electrically evoked displacements capable of producing high-fidelity, high-frequency acoustic energy. The electrically evoked intra-cochlear energy results in conventional traveling waves within the cochlea, as well as emissions of sound from the cochlea. These data provide direct support for a mechanism of cochlear sensitivity and tuning involving high-frequency OHC electromotility. Moreover, the data also indicate that any intra- or extracochlear electric current which affects the electric polarization of OHCs could induce BM traveling waves and cause 'electromotile hearing'. This form of hearing would be one component under the more general definition of the electrophonic effect.

Animals↗

Extracochlear electrically evoked otoacoustic emissions: a model for in vivo assessment of outer hair cell electromotility.

Cochlear outer hair cell (OHC) motion in response to changes in membrane potential (electromotility) has been extensively studied in vitro. Electromotility is thought to actively control the micromechanical properties of the sensory epithelium. In order to understand how OHC electromotility contributes to normal cochlear responses, its role must be assessed in vivo. We have developed a novel animal model for the study of electromotility in vivo. Alternating current is delivered by an electrode to the round window (RW) of gerbil cochlea and the electrically evoked otoacoustic emission (EEOE) is measured from the external ear canal. As much as 45 dB SPL sound could be generated by about 200 micro A RMS extracochlear current delivered to the RW. Except for the fine structure of EEOE transfer function curves, the magnitude of the EEOE has a bandpass appearance ranging from about 4 to 32 kHz and shows a positive linear relationship to the current intensity. The phase has a linear relationship with frequency and shows no significant change with current intensity. Local intracochlear perfusion of 4% paraformaldehyde caused EEOE to decrease by approximately 20 dB. These results indicate that the EEOE is probably generated by OHCs near the electrode location and propagates to the external ear canal. In addition, the force generated by OHCs in vivo is a linear function of the electrical stimulus. The major advantages of our model include: (1) non-invasive procedure and normal cochlea; (2) wide dynamic range of the measurement; (3) simple and easy preparation. With these features this model has potential applications in basic hearing research and in the diagnosis and treatment of otological patients.

Animals↗

Studies of inner ear blood flow in animals and human beings.

This article reviews current studies on inner ear blood flow, discusses their relevance to the maintenance of normal homeostasis of the inner ear, reports for the first time clear changes in fundamental properties of cochlear blood flow in the chronic hydropic ear, and describes the potential of applying laser Doppler flowmetry technology to the measurement of inner ear blood flow in human beings. Studies of the guinea pig in which perfusion pressure is varied demonstrate a broad range of autoregulatory capabilities of the inner ear vasculature. Gain factors range from 0.76 and higher for recovery for less than 1 minute of modified perfusion pressure. This is significantly greater than reports obtained for brain autoregulation. In a series of four investigations of cochlear blood flow in the hydropic ear in guinea pigs, a decreased responsiveness to electrical stimulation and direct stimulation of the superior cervical ganglia was found, indicating a change in sympathetic control of cochlear tone. Reduced vasomotion was observed, and autoregulatory capabilities were reduced. In human investigations, changes in cochlear blood flow were demonstrated with direct electrical stimulation of the round window and warm water irrigation of the ear canal, but not with carbogen breathing. Increased cochlear blood flow was observed with increased systemic blood pressure, and a remarkable decrease in cochlear blood flow was observed with the application of 1:10,000 epinephrine to the round window. These observations indicate the potential for development of laser Doppler flowmetry technology in the diagnosis and treatment of inner ear vascular disorders, and the animal investigations suggest that changes may occur in the chronic hydropic ear that compromise autoregulation and thus increase the sensitivity of the hydropic ear to other stress factors. Treatments can be found to modify such changes in vascular tone.

Animals↗