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Biomedical subjects

A L Nuttall

Publications and source records attributed to A L Nuttall.

At least 73 records · Page 4Linked to original sources
PubMed1995

Hydrops-induced changes in cochlear blood flow.

Laser Doppler flowmetry was used to assess cochlear blood flow (CBF) in the hydropic ear in four experiments. 1) The increase in CBF elicited by local electrical stimulation of the cochlea in the hydropic ear was compared to that observed in normal controls. The magnitude of the evoked CBF change was reduced by approximately 30% in the hydropic ear compared to the normal ear. 2) The reduction in CBF evoked by direct electrical stimulation of the superior cervical ganglion was reduced by approximately one third in the hydropic ear compared to a normal ear. 3) Rhythmic (flux motion or vasomotion) variations in CBF, observed in association with lower blood pressure and thought to extend the autoregulatory range in an organ system, were reduced or eliminated in the hydropic ear. 4) The autoregulatory response to a decreased perfusion pressure, produced by decreased cardiac output, was clearly reduced relative to control in the hydropic ear. These findings represent the first report of significant CBF changes with hydrops. They are consistent with reports of increased sensitivity of the hydropic ear to trauma and stress and may be relevant considerations in the treatment of hydrops in humans.

Animals↗
PubMed1995

Heart beat modulation of spontaneous otoacoustic emissions in guinea pig.

It has been reported that background variation in the frequency of spontaneous otoacoustic emission (SOAEs) may arise from the cardiovascular system and that the side-bands in the spectra of SOAEs may be modulated by heartbeat. For better understanding of the mechanical influence of the cardiac cycle on cochlear functions under physiological and pathophysiological conditions, this study investigated heartbeat-induced modulation of SOAEs in guinea pig. Possible mechanisms of these phenomena are also discussed. The external ear canal acoustic signal, round window electric signal, and the ECG were recorded for off-line analysis from five pigmented guinea pigs with SOAEs. Time and frequency domain averages with synchronization of the heartbeat indicate that both the external ear canal acoustic and round window electric signal contain some component contributed by ECG and phonocardiography. High resolution FFT spectra suggest that SOAEs were modulated by heartbeat and respiration. Theoretically the change in the SOAEs could be from frequency modulation or a combination of frequency and amplitude modulations. Results of a heartbeat-synchronized average of a wave analyzer output at SOAE frequency indicates that amplitude modulation of SOAE does occur. Data obtained in the current experiment support the hypothesis that the heartbeat-related modulation of SOAE in guinea pig is a combination of frequency and amplitude modulation. The proposed mechanism is that pulsatile cochlear blood flow may cause oscillations in cochlear pressure and affect cochlear performance, resulting in heartbeat modulation of SOAEs.

Animals↗
PubMed1995

Effect of endolymphatic hydrops on capsaicin-evoked increase in cochlear blood flow.

Capsaicin, which causes release of neuropeptides including substance P, has been shown to cause dose-related increases in cochlear blood flow (CBF). Since CBF regulation is altered in animal models with endolymphatic hydrops, this study was designed to examine the effect of hydrops on capsaicin-induced CBF changes. CBF responses to 0.01 and 0.001% capsaicin applied to the round window membrane were measured in normal and 12-week hydropic guinea pigs using laser Doppler flowmetry. With 0.01% capsaicin, CBF increased by only 13 +/- 7.8% in the hydropic ear, compared with 34% +/- 13% in the normal animal (p = 0.027). With 0.001% capsaicin, CBF increased by only 7.5 +/- 4.2% in the hydropic ear, compared with 28 +/- 16% in the normal ear (p < 0.001). These findings demonstrate a reduced responsiveness to capsaicin with endolymphatic hydrops and suggest that hydrops causes an alteration in the peptidergic sensory fibers of the inner ear or in the vascular smooth muscle or both. The results are consistent with previous reports of reduced vascular responsiveness in hydropic guinea pigs and provide further evidence for abnormal CBF regulation in hydrops.

Alkaloids↗
PubMed1994

Neuronal regulation of cochlear blood flow in the guinea-pig.

1. Previous studies have shown that electrical stimulation (ES) of the guinea-pig cochlea causes a neurally mediated increase in cochlear blood flow (CBF). It is known that the centrifugal neuronal input to the cochlea comes through the perivascular sympathetic plexus from the cervical sympathetic chain and along the vestibular nerve (VN) from the periolivary area of the brainstem. Both of these neuronal systems are distributed topographically in the cochlea. 2. In order to study the neural origins of ES-evoked CBF increase, laser Doppler flowmetry was used to test the following hypotheses. (a) The response is regional, that is, limited to the area of the cochlea stimulated. To test this we performed differential ES of the cochlear turns. CBF was measured from either the third or the first turn. (b) The response is mediated via autonomic receptors within the cochlea. To study this, we applied atropine, succinylcholine and idazoxan locally to the cochlea. (c) The response is influenced by neuronal input via the sympathetic cervical chain (SC) and components of the VN. We stimulated and sectioned the SC, and sectioned the VN, to test this hypothesis. 3. We observed that the CBF response was topographically restricted to the stimulated region. Locally applied muscarinic or nicotinic antagonists (atropine and succinylcholine respectively) did not affect the response. However, local idazoxan (an alpha 2-blocker) eliminated the response. Locally applied adrenaline and SC stimulation modified the dynamic range of the response. SC sectioning enhanced the responsiveness of the cochlear vasculature to ES. The VN section caused a temporary decrease in CBF and elimination of the ES-evoked CBF response. 4. We conclude that the release of dilating agents is topographical with respect to ES current flow, the ES-evoked CBF increase is peripherally mediated via alpha 2-receptors, and the response is influenced by input via the SC. The elimination of the response by VN sectioning proximal to the brainstem indicated that fibres of the VN mediate the CBF increase during direct cochlear ES. The data suggest that these fibres may be the efferent limb of a neural loop involved with the regulation of CBF. Such a system could provide a mechanism for the rapid increase in CBF with organ stress.

Adrenergic alpha-Antagonists↗
PubMed1994

Basal nitric oxide production in regulation of cochlear blood flow.

Nitric oxide (NO), recently identified as endothelium-derived relaxing factor, has been shown to influence both vascular and neural function. In blood vessels, NO is produced by endothelial and smooth muscle cells and may play a role in regulation of cochlear blood flow. In the central nervous system, NO functions as a neurotransmitter involved in long term potentiation. The principle hypothesis tested in this study was that basal NO production in the cochlear blood vessels contributes to regulation of CBF. Since NO is a vasodilator, diminished NO synthesis may decrease the level of CBF. Application of a competitive inhibitor of NO synthase either intravenously or to the round window membrane caused a reduction in CBF. The application to the round window membrane did not affect compound action potential thresholds. With intravenous administration, the effect on CBF was dose-related and could be reversed with the physiologic substrate, L-arginine. These data indicate that NO is produced in the cochlear blood vessels and contributes to the regulation of CBF.

Action Potentials↗
PubMed1994

Cochlear blood flow measured by averaged laser Doppler flowmetry (ALDF).

This report describes a new approach to estimate the hydromechanical properties of a vascular system. Averaged laser Doppler flowmetry (ALDF) was developed by averaging the flux signal of a laser Doppler flowmeter (LDF) synchronized to the heart cycle. The usefulness of this method was verified by manipulation of the cochlear microvasculature. Twelve pigmented guinea pigs under pentobarbital/fentanyl anesthesia were used. The cochlea was surgically exposed and the LDF probe placed on the bony surface of the first turn to monitor cochlear blood flow (CBF). The LDF flux signal (0.2 s time constant) was sampled by an A/D board at 2 kHz for 255 ms and averaged with synchronization to the heart beat. The mean blood flow, peak to peak amplitude, and time (phase) delay of pulsatile flow were measured from the averaged signal. According to a transmission line model of the vascular system, under a given perfusion pressure, mean flow reflects resistance while amplitude and time delay of the pulsatile flow are related to the reactance component of the impedance of the vascular system. During the formation of photochemically-induced thrombosis in the cochlear microvasculature, there was a dramatic mean flux decrease (90.1 +/- 3.4% from baseline (BL), N = 6). Additionally, a time-dependent decrease in amplitude and time delay of pulsatile flow were indicated by ALDF. These results suggest a large increase in vascular resistance and significant decrease in compliance.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

Effects of vasodilating agents on cochlear blood flow in mice.

The mouse has several distinct advantages as an experimental model for study of the cochlear blood flow (CBF) in the mammal, particularly for studies involving genetic manipulation, development and aging factors. In this investigation we evaluated the effects of selected vasodilating agents on CBF using laser-Doppler flowmetry. Sodium nitroprusside, hydralazine and pentoxifylline were applied topically on the round window (RW) or systemically by a subcutaneous injection. Topical application of sodium nitroprusside and hydralazine elevated CBF significantly, while systemic administrations of these two drugs failed to elevate CBF consistently. Pentoxifylline did not change CBF following topical application but increased CBF slightly following systemic administration. Age and gender did not influence the CBF response to topical application of sodium nitroprusside.

Administration, Topical↗
PubMed1994

Comment on "Modulation of the hair cell motor: a possible source of odd-order distortion" [J. Acoust. Soc. Am. 96, 2210-2215 (1994)].

This reply to the response by Brown [J. Acoust. Soc. Am. 96, 2210-2215 (1994) on the report "Intermodulation distortion (F2-F1) in inner hair cell and basilar membrane responses [J. Acoust. Soc. Am. 93. 2061-2068 (1993)]" by Nuttall and Dolan is for the purpose of adding additional data concerning the nature and origin of the round window (RW)-recorded quadratic distortion tone (QDT) signal. It is shown that a major portion of the RW electrical signal originates from the activity of auditory neurons since tetrodotoxin (TTX) applied to the cochlea diminished the distortion product by about 75%. The neural component is also responsible for the characteristic 900-Hz optimal frequency separation of the primaries in producing the response. These data support our earlier suggestion [Nuttall and Dolan, J. Acoust. Soc. Am 93, 2061-2068 (1993)] that the level of intracellular receptor potential at the QDT frequency would be a stimulus for afferent fibers at low sound levels. These new data do not force a reinterpretation of Brown's hypothesis on the relationship of quadratic and cubic intermodulation distortion.

Ear, Inner↗
PubMed1994

Autoregulation of cochlear blood flow in guinea pigs.

Autoregulation of blood flow in the inner ear following uncontrolled changes in systemic blood pressure (BP), which was induced by the application of pharmacological agents that cause local and/or systemic vascular effects, has been reported in previous studies. In the current study, carotid BP was systematically manipulated without drugs, while the resulting cochlear blood flow (CBF) changes were measured using a laser Doppler flowmeter (LDF). Anesthesized guinea pigs were used, and the probe of a LDF was held against the ventral-posterior portion of the surgically exposed cochlea. A mechanical occluder was placed around the descending aorta or the inferior vena cava. BP could be elevated or lowered over a wide range and was held stable during 2-min occlusions. The mean level (+/- SD) of regulation (% delta CBF/% delta BP) for BP changes less than +/- 35% of preocclusion baseline was 0.24 +/- 0.2 (or 0.18 +/- 0.2 if BP is corrected by subtracting central venous pressure). Significant regulation occurred for BP between 20 and 70 mmHg. A demonstration of the cochlear origin of the regulatory response was obtained by "pharmacological blockade" following topical application of the vasodilator, sodium nitroprusside, to the cochlea. In this condition, CBF changed in nearly direct proportion to BP.

Animals↗
PubMed1994

Dynamic response of cochlear blood flow to occlusion of anterior inferior cerebellar artery in guinea pigs.

In this study we investigated the autoregulation and hemodynamics of cochlear blood flow (CBF) as measured by laser-Doppler flowmetry. When the anterior inferior cerebellar artery was clamped, CBF decreased approximately 40% (not to "biological zero"), followed by a gradual increase. When the clamp was released, CBF quickly increased to as much as 167% of the baseline level and then slowly returned to baseline. We assume that the dynamic CBF response to anterior inferior cerebellar artery clamping reflects primarily a combination of passive elastic properties of the cochlear vessels and active autoregulatory mechanisms. The decrease portion of the negative phase and the increase portion of the positive phase reflect mainly passive behavior, static compliance, and resistance of vessels, whereas the slow exponential negative and positive changes indicate an active response of vessels: an autoregulatory mechanism based on compensatory vascular dilation and constriction. Our preliminary data show a very strong CBF autoregulatory response to a change in intravascular pressure. Sympathetic stimulation can enhance this autoregulation, and CO2 inhalation promotes compensatory dilation and inhibits compensatory vascular constriction.

Animals↗
PubMed1994

Cochlear flux motion and arterial pressure reduction in guinea pig.

Vasomotion, as a fundamental phenomenon of microvessels, exists in the cochlea of guinea pig. In the current study, the vasomotion and its relation to arterial pressure reduction was studied in the guinea pig cochlea, using laser Doppler flowmetry (LDF). Blood pressure (BP) in 25 guinea pigs was manipulated by a mechanical occluder placed around the descending aorta or the inferior vena cava. Before thoracotomy and artificial respiration, BP was 55.5 +/- 10.9 mmHg and no flux motion occurred. Vasomotion became evident when BP was significantly lower (28.2 +/- 7.2 mmHg) than the mean BP after thoracotomy (37.3 +/- 8.3 mmHg) (t = 4.1536, p < 0.05). Vasomotion appeared during both continuous hypotension and brief BP decreases caused by mechanical occlusion. During periods of continuous flux motion, both increase and decrease in BP could weaken or abolish it. The pressure provoking the vasomotion was different for each animal but the pressure range for a given animal was relatively stable. Mean frequency and amplitude of flux motion were 3.8 +/- 0.6 cycles per min and 20.8 +/- 7.1% of the baseline. A negative linear relationship was found between amplitude and frequency. Oscillations of LDF signal indicate that there is a synchronization of contraction and relaxation of cochlear microvessels or of the larger supplying vessels to the cochlea. Manipulation of BP possibly initiates the fluctuating change in vascular tone by influencing the activity of pacemaker or feedback mechanisms of cochlear vascular smooth muscles.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

Influence of calcitonin-gene related peptide on cochlear blood flow and electrophysiology.

Intra-arterially infused calcitonin gene-related peptide (CGRP) induced dose-dependent decreases in both systemic blood pressure and cochlear blood flow (CBF). However, when subjects were pretreated systemically or locally with the specific receptor antagonist CGRP(8-37), CBF increased, despite decreases in systemic blood pressure in response to CGRP infusions. Micro-infusions of CGRP directly into the supplying arterial network of the cochlea induced dose-dependent increases in CBF that were blocked by CGRP(8-37) pretreatment. Cochlear electrophysiology, as assessed by cochlear action potential and cochlear microphonics, remained unchanged following each condition tested. These results indicate that CGRP is involved in systemic regulation of blood pressure and contributes to the regulation of CBF.

Animals↗
PubMed1993

Three-dimensional analysis of contrast-filled microvessel diameters.

Organ blood flow is controlled, in part, by changes in diameter of resistance vessels. In thick tissue, vessels can be imaged with a microscope using contrast-enhancing methods (e.g., fluorescence) and image analysis techniques can be used for quantitative diameter estimations. However, a change in the position of a vessel with respect to the plane of focus can be misinterpreted as a diameter change. In order to address this problem, a 3D image in a light microscope is obtained by serial optical sectioning, and a 3D deconvolution procedure (Avinash et al., 1991, "Fourteenth Association for Research in Otolaryngology Midwinter Meeting, St. Petersberg, FL," Abstract 156) is used to deblur 3D image data. Deblurred sections are computationally projected onto a 2D plane to give an extended-focus image, from which diameter estimates of microvessels are made using a quantitative, 2D diameter-tracking algorithm (Miles, 1987, "Semiautomatic Quantitative Image Analysis of Dynamic in Vivo Cochlear Microvessel Diameters." Ph.D. dissertation, Univ. Michigan; Miles and Nuttall, 1992, IEEE Trans. Biomed. Eng.). Justification for 3D preprocessing before diameter analysis is provided by absolute and relative error analyses using computer-generated synthetic vessels. The 3D diameter analysis technique is validated using a capillary tube of known diameter, filled with fluorescent solution. Demonstration of its applicability is shown in diameter measurements from the vessels of guinea pig cochlea. Our approach, using extended-focus images, minimizes overestimation of microvascular diameters and underestimation of relative diameter changes. Therefore, unambiguous diameter measurements are possible with extended-focus images.

Algorithms↗
PubMed1993

Stellate ganglion drives sympathetic regulation of cochlear blood flow.

The functional properties of the sympathetic fibers innervating the cochlea are not well understood. Adrenergic fibers supplying lateral wall structures of the cochlea have been observed terminating on radiating arterioles and collecting venules. Adrenergic fibers also terminate as 'free' endings in the spiral osseous lamina. Stimulation or transection of sympathetic fibers originating from superior cervical chain and supplying the cochlea have yielded mixed results concerning many aspects of cochlea physiology. In order to clarify the origin of sympathetic fibers and their role in control of cochlear blood flow (CBF), we examined the effect of electrical stimulation of the stellate ganglion (ESS) and transection of postganglionic fibers from the stellate on CBF measured by laser Doppler flowmetry and on systemic blood pressure (BP) in the guinea pig. ESS produced a 20-35% increase in BP and 10-15% decrease in CBF. The decrease in CBF presumably reflects the net result of increased perfusion pressure, local autoregulatory mechanisms, and a direct sympathetic-induced vasoconstriction. Section of the immediate postganglionic sympathetic trunk had little or no effect on the ESS-related change in BP; however, it eliminated the CBF reduction. Intravenously infused beta 1-blocker diminished the BP increase due to ESS, while the electrically-evoked reduction in CBF remained. Local application of an alpha-blocker on the round window blocked ESS evoked CBF reductions without altering the BP increase. These data confirm the functional role of sympathetic projections from the stellate ganglion in CBF regulation in guinea pig.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic Fibers↗
PubMed1993

Contribution of the anterior inferior cerebellar artery to cochlear blood flow in guinea pig: a model-based analysis.

This study was performed to determine the contribution of the anterior inferior cerebellar artery (AICA) to cochlear blood flow (CBF) in guinea pig. The AICA and the basilar-vertebral arterial complex in twelve animals was exposed through the basal portion of the skull. The cochlea was ventrally approached and the CBF of the apical area monitored with laser Doppler flowmetry. A specially designed microclamp was held in a micromanipulator and used to obstruct the AICA. When the AICA was clamped, CBF decreased to approximately 60% of baseline (BL) (not to 'biological zero'), followed by a gradual increase. When the clamp was released, CBF quickly increased to more than 160% BL and then slowly declined to baseline. To quantify the contribution of AICA to CBF, we formulated an electrical analog model of the cochlear vessel system. With this model, AICA contribution to CBF and the relationship among blood pressure, blood flow, and vascular resistance or vascular conductance in the cochlea can be explored. Results in the present study indicate that the AICA contributes only about 45% of CBF to the cochlea; 55% of CBF must come from other supplying vessels. Contrary to previous reports, CBF response to AICA clamping did not exhibit a stable or constant decrease but showed time-dependent dynamic changes. In addition, the cochlear vascular system showed a marked autoregulatory response, instead of a passive response, to the perfusion pressure change. AICA clamping is, therefore, not a suitable model for investigation of ischemia effects in the guinea pig cochlea, but it is a useful approach to study autoregulation and the myogenic mechanism of the cochlear vascular system.

Animals↗
PubMed1993

Substance P increases cochlear blood flow without changing cochlear electrophysiology in rats.

Carotid artery infusions of substance P yielded reductions in systemic blood pressure and elevations in cochlear blood flow (CoBF), measured via laser Doppler flowmeter, with no alterations in cochlear action potentials or cochlear microphonics in Wistar-Kyoto rats. Additionally, direct micro-infusions of substance P into the anterior inferior cerebellar artery, which contributes to the local vascular perfusion of the cochlea, yielded elevations in CoBF with no changes in systemic blood pressure. Pretreatment with a specific substance P receptor antagonist, ([D-Pro2,D-Trp7,9]SP) via the carotid artery or the anterior inferior cerebellar artery, diminished subsequent substance P-induced vascular responses. These results suggest that endogenous substance P, like other vasoactive peptides, may interact with a substance P-specific receptor population in the cochlea and may therefore participate in the ongoing regulation of CoBF. These findings also support the premise that vasodilatory hormones, along with vasoconstrictive agents, may be involved in the autoregulation of CoBF.

Action Potentials↗
PubMed1993

The vascular component of sodium salicylate ototoxicity in the guinea pig.

Drugs of the salicylate family (aspirin-like drugs) are reversibly ototoxic. Electrophysiologic and ultrastructural evidence suggests an impairment of the sensory hair cells of the cochlea following salicylate treatment. In addition, since these drugs can cause vasoconstriction, the ototoxicity of salicylates may also involve an impairment of the blood circulation in inner ear. However, a vascular hypothesis of salicylate toxicity has not received much attention. In the current study, we simultaneously measured cochlear blood flow (by laser Doppler flowmetry) and the sound-evoked potentials from the round window. Sodium salicylate caused a decrease in cochlear blood flow that appeared within 30 min following an intramuscular injection of a low dose of sodium salicylate (100 mg/kg). This sodium salicylate dose did not cause a change in auditory sensitivity. For higher doses (200 mg/kg and 300 mg/kg), both cochlear blood flow and auditory sensitivity were affected. The 300 mg/kg dose decreased blood flow by about 25% and elevated compound action potential thresholds by 10 to 25 dB for high frequencies (> or = 8 kHz). Further experiments showed that salicylate-induced threshold shifts were significantly reduced for the mid-frequencies when cochlear blood flow is increased by the vasodilating drug hydralazine (negating the flow reduction caused by salicylate). These data indicate that in addition to the direct effect of systemically administered salicylate on neurosecretory function a decreased blood flow contributes to the ototoxicity of salicylates.

Action Potentials↗