Biomedical subjects

A L Nuttall

Publications and source records attributed to A L Nuttall.

At least 109 records · Page 6Linked to original sources

PubMed1991

Noise-induced changes in red blood cell velocity in lateral wall vessels of the rat cochlea.

The effects of loud sound on the microvasculature of the cochlea are not well characterized or understood. Morphological changes in the stria vascularis and changes in blood flow are known to occur during or following sound stimulation, however, the effects on cochlear blood flow appear to be complex. Studies have shown that noise exposure may produce increases in blood flow, decreases in blood flow, or no measureable change in blood flow. These inconsistent results probably reflect the various noise exposure parameters, the animal model used, and could be a function of the specific procedures utilized to assess blood flow changes. The purpose of the current study was to investigate the effects of one specific class of sound exposure (high intensity noise) on red blood cell velocity in the capillaries of the second turn of the rat cochlea using intravital microscopy. This class of sound exposure was selected in order to attempt a confirmation of previous findings of increased blood flow (Perlman and Kimura, 1962) using the quantitative technique of red blood cell velocity measurement. Following determination of pre-exposure red blood cell velocities in capillaries of the rat cochlea second turn, animals were exposed to 133 dB or 110 dB broad-band noise for ten minutes. The red blood cell velocity was recorded continuously during the exposure. Exposure to both sound intensities disrupted stable and orderly baseline flow patterns and resulted in overall intensity-dependent increases in red blood cell velocity.(ABSTRACT TRUNCATED AT 250 WORDS)

Acoustic Stimulation↗

PubMed1991

Influence of topically applied adrenergic agents on cochlear blood flow.

This study was designed to assess the role of adrenergic receptors in the control of cochlear blood flow. Laser Doppler flowmetry was used to determine the effects of adrenergic drugs topically applied to the round window membrane of the cochlea. The relative influence of the various receptor types (alpha 1, alpha 2, beta 1, and beta 2) was examined by a selection of agonists and antagonists. The agonists norepinephrine and epinephrine, which have mixed alpha- and beta-receptor effects, and phenylephrine, a strong alpha 1-agonist, all induced a dose-dependent reduction in cochlear blood flow. The agonists isoproterenol (beta-active), salbutamol (alpha 2-active) had no effect on cochlear blood flow. Of the antagonists, when tested alone, only the selective alpha 1-antagonist prazosin had a direct effect on cochlear blood flow, demonstrating an increase in cochlear blood flow. The selective alpha 2-antagonist idazoxan, the beta-antagonist propranolol, and the unselective alpha-antagonist phentolamine had no effect on cochlear blood flow. Interaction studies of agonists and antagonists were performed to specifically define the receptor subclasses responsible for the cochlear blood flow increases with norepinephrine and epinephrine. The results are consistent with the presence of an alpha 1-adrenergic sympathetic control of cochlear blood flow.

Administration, Topical↗

PubMed1991

The protective effects of allopurinol and superoxide dismutase-polyethylene glycol on ischemic and reperfusion-induced cochlear damage.

The purpose of this study was to assess the protective effects of allopurinol, a blocker of free oxygen radical (FOR) formation, and superoxide dismutase-polyethylene glycol (SOD-PEG), a scavenger of FORs, on ischemic and reperfusion-induced cochlear damage. Fifteen Wistar Kyoto rats (WKY) were randomly assigned to three groups: (1) a control group (5 animals) that was exposed to 15 minutes of cochlear ischemia by clamping the anterior inferior cerebellar artery (AICA), followed by 15 minutes of reperfusion as documented by laser Doppler flowmetry; (2) a drug-treated group (5 animals) that received allopurinol before ischemia/reperfusion; and (3) a drug-treated group (5 animals) that received SOD-PEG before ischemia/reperfusion. In the control group, the tone burst-evoked compound action potential (CAP) recorded from the round window (RW) of the cochlea was abolished, and the cochlear microphonic (CM) was reduced after ischemia. In contrast, both allopurinol and SOD-PEG-treated animals showed post-reperfusion sensitivity in CAP and CM measures. We interpret these results to indicate that damage to the cochlear from ischemia and subsequent reperfusion can be attenuated by pretreatment with allopurinol or SOD-PEG. This provides indirect evidence that FORs may be partially responsible for cochlear damage resulting from ischemic conditions.

Action Potentials↗

PubMed1991

Microvessel diameter estimation: error bias correction of serial measurements.

The assessment of vessel patency can be substantially improved by serial microvessel diameter measurements taken successively along an extensive length of the vessel. It is possible to avoid making the a priori assumptions about the existence or location of local constriction sites implicit in single diameter measurements. The problem then becomes one of making sense of tens or hundreds of measurements for each vessel. Equivalent diameter is defined here as as the diameter of a uniform circular cylinder of the same length as the original vessel, and having the same total resistance. Direct computation of the equivalent diameter, without taking measurement errors into account, leads to an underestimation of the true equivalent diameter even if the individual diameter measurements were not biased. We have developed a method for effectively eliminating this bias. It has been applied to serial microvessel diameter measurements of the guinea pig cochlea, automatically measured using an image analysis system. In this report, the results were developed for diameter estimates with an approximate gaussian distribution; however the method is readily extended to other error distributions. Convergence of the bias compensation was rapid. Use of the new method is advisable with as few as three diameter estimates per vessel.

Animals↗

PubMed1990

Laser Doppler measurements of cochlear blood flow during loud sound presentation.

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.

Animals↗

PubMed1990

Inner hair cell responses to the 2f1-f2 intermodulation distortion product.

Recordings of dc and ac receptor potentials from pigmented guinea pig inner hair cells indicate strong responses to the 2f1-f2 intermodulation tone when f1 and f2 are greater than the hair cell characteristic frequency and do not cause a response when given individually. The effective magnitude of this cubic distortion product (CDP) was about 25-30 dB below equal sound level primaries over a 20-30-dB range of their sound levels. The relative strength of the CDP declined at a rate greater than 180-dB/oct separation of the primaries. When magnitude of f1 or f2 was held constant, the growth of CDP was nonmonotonic, exhibiting a distinct maximum. With a constant level of f1 or f2, optimal CDP was produced when the level of f2 was 10-15 dB greater than f1. Strong two-tone suppression from the primaries has a role in shaping the CDP growth. The ac receptor potentials of the CDP show a 150 degrees-200 degrees phase shift when the primaries are increased over a 50-dB range. These results support the hypothesis of a propagated CDP in the cochlea and are consistent with the major features of related studies of human psychoacoustic experiments, afferent nerve neural rate functions, and ear canal distortion products.

Acoustic Stimulation↗

PubMed1990

Asynchronous neural activity recorded from the round window.

Voltage recorded from an electrode on the round window (RW) of guinea pig has characteristics that reflect the activity of auditory-nerve fibers in the absence of acoustic stimulation. Fast Fourier transformation (FFT) of the noise recorded from the RW electrode shows a broad spectral peak from 0.8-1.0 kHz. The magnitude of the biological noise is increased by high-frequency, bandlimited acoustic noise stimulation. Pure tones can suppress or enhance the spectral components around 0.8-1.0 kHz depending on frequency and intensity. Kainic acid applied to the intact RW membrane eliminates the biological noise (and the evoked cochlear whole-nerve responses) without alteration of the cochlear microphonic or the summating potential. The spectral characteristics of the biological noise seem to be related to the elemental waveform contributed by the individual auditory-nerve fibers to the voltage recorded at the RW electrode [Kiang et al., Electrocochleography, edited by R. J. Ruben, C. Elbering, and G. Solomon (University Park, Baltimore, 1976)].

Animals↗

PubMed1989

Inner hair cell responses to tonal stimulation in the presence of broadband noise.

The effects of broadband noise (BBN) on the tone-evoked de receptor potential from inner hair cells of guinea pigs were measured. The effects of the noise were: suppression of the receptor potential, no net change, or greater depolarization relative to the tone alone, evoked receptor potential. The effects appear to be consistent with a two-tone suppression hypothesis. The time course of the suppression effect is immediate and constant in time. This observation suggests no obvious involvement of a local feedback loop in outer hair cells or one depending on the efferent nerves. Inner hair cell "sensitivity" is a variable in the magnitude of the suppression. Comparison of masked, tone-evoked de receptor potential intensity functions to responses from auditory-nerve fibers (taken from the literature for experiments using a similar paradigm) differentiates the phenomena of suppression and adaptation in the auditory periphery.

Acoustic Stimulation↗

PubMed1989

Characterization of an EPSP-like potential recorded remotely from the round window.

The whole-nerve cochlear action potential (CAP), to tone burst stimulation, was recorded before and after application of tetrodotoxin (TTX) to the intact round window (RW) membrane. TTX abolished the CAP leaving a residual negative potential without altering the summating potential (SP) or the cochlear microphonic (CM). The residual potential retained its polarity when recorded from scala vestibuli. The peak latency, amplitude, and tuning properties of the residual potential showed features similar to the CAP. Application of kainic acid to the RW membrane eliminated the residual potential, leaving the SP and CM unaltered. It is hypothesized that the sources of the residual potential are the excitatory post-synaptic potentials from the peripheral processes of afferent dendrites under the inner hair cells.

Acoustic Stimulation↗

PubMed1989

Electrically stimulated increases in cochlear blood flow: I. Frequency and intensity effects.

Charge-balanced, sinusoidal current was passed differentially between the apex and round window of the guinea pig cochlea. Cochlear blood flow was measured using a laser Doppler flow monitor. Systemic blood pressure was monitored from a cannula within the common carotid artery. Electrical stimulation increased cochlear blood flow, while systemic blood pressure was unaffected. A cochlear blood flow response parameter, normalized for transient changes in systemic blood pressure, was defined. The magnitude of the response parameter was found to be frequency selective and was also found to be an increasing function of current intensity, with maximum responses obtained with 500 Hz sinusoids. This cochlear blood flow response was not observed in dead animals; was present in preparations paralyzed with gallamine hydrochloride; and was correlated with an increase in cochlear red blood cell velocity, as directly observed by intravital microscopy. These observations imply that electrical stimulation induces a local vasodilation within the temporal bone. The fact that decreased cochlear blood flow was never observed with current injection implies that ischemia is not a likely mechanism of electrically induced tissue damage within the inner ear. The mechanism of this cochlear blood flow response is addressed in a companion report.

Animals↗

PubMed1989

Electrically stimulated increases in cochlear blood flow: II. Evidence of neural mediation.

In a companion paper, we reported that electrical stimulation increased cochlear blood flow (CBF). This response was found to be an increasing function of current intensity and was frequency-selective, with the best response at approximately 500 Hz continuous sinusoidal current. The present investigation seeks to discover the mechanism of this effect. Direct measurement of cochlear temperature during electrical stimulation revealed no evidence of local heating. Autonomic neuronal activation is not likely, as neither atropine, hexamethonium, nor propranolol abolished the evoked CBF response. Strial activity could be suppressed by the use of furosemide, but the evoked CBF response persisted. Inactivation of auditory afferent neurons with kainic acid also did not change the evoked CBF response. Dimethyl sulfoxide, a potent oxygen-free radical scavenger, did suppress the evoked CBF response to a small but significant degree. This suggests that oxygen-free radicals may be produced within the cochlea during electrical stimulation. Finally, the evoked CBF response was completely suppressed by procaine and tetrodotoxin, with recovery of evoked CBF response accompanying recovery of cochlear action potentials. These data indicate that stimulation of neural fibers, distinct from autonomic and auditory afferent neurons, may modulate CBF.

Animals↗

PubMed1989

A comparison of laser Doppler and intravital microscopic measures of cochlear blood flow.

Many inner ear disorders may be caused by alterations in cochlear blood flow (CBF). However, each measurement technique used to monitor CBF has limitations in examining the relationship between otopathologic states and blood flow. This study investigates laser Doppler flowmetry (LDF) and its fundamental drawback: the unknown relationship of LDF output to actual CBF. LDF readings are directly compared with concurrent intravital microscopy (IVM) measures of erythrocyte velocity in the lateral wall of the guinea pig cochlea. Positive end expiratory pressure, spontaneous respiration of 5% and 10% carbon dioxide, phenylephrine, and direct electrical stimulation of the cochlea were used to manipulate CBF. High, positive correlations were found between simultaneous LDF and IVM measurements of CBF. In addition, the study demonstrated that current microdissection techniques used to perform IVM do not cause changes in CBF. IVM measurements of CBF are a more sensitive indicator of CBF changes than are LDF measures. Despite the high correlation between measurement techniques within a single manipulation, simultaneous LDF and IVM measurements differed between manipulations. This may reflect regional changes in CBF affected by these manipulations and differences in the sampled vascular beds contributing to these two measures. It is unlikely that a single calibration factor can be defined that would allow the conversion of LDF output to actual units of blood flow across different manipulations used to alter CBF.

Animals↗

PubMed1989

Blood pressure and other physiological responses in awake and anesthetized guinea pigs.

The effect of combinations of injectable anesthetics on mean arterial blood pressure, blood gases, heart rate and respiration of the guinea pig (NIH Outbred strain) was investigated. After a 30 minute period in which baseline resting cardiorespiratory measurements were obtained, five groups of six pigmented animals having indwelling carotid cannulas were anesthetized with (a) ketamine hydrochloride (30 mg/kg, im)/xylazine (5 mg/kg, im); (b) sodium pentobarbital (15 mg/kg, ip)/fentanyl-droperidol (0.4 mg/kg, im); (c) diazepam (5mg/kg, ip)/fentanyl citrate (0.32 mg/kg, im); (d) diazepam (5 mg/kg, ip)/alphaxalone-alphadolone acetate (45 mg/kg, im); or (e) 1% alpha-chloralose-40% urethane (0.8 ml/100g, ip). Animals were not respirated artificially and no supplemental doses of anesthetic were given. Resting blood pressure in awake animals was measured over time for as long as cannulas remained patent (109 measurements). Mean resting blood pressure, for this strain of guinea pigs, was determined to be 53.1 +/- 4.2 mmHg. There was no indication that mean arterial blood pressure changed with age in animals varying in weight from 215 g to 550 g. Under diazepam/fentanyl, blood pressure rose significantly above resting level to a mean of 71.1 +/- 6.1 mmHg. With the other four combinations, blood pressure stabilized near, but below pre-anesthesia levels (ketamine/xylazine 47.1 +/- 6.8 mmHg; pentobarbital/fentanyl-droperidol, 46.9 +/- 3.2 mmHg; diazepam/alphaxalone-alphadolone, 47.8 +/- 4.8 mmHg; chloralose-urethane, 51.0 +/- 1.2 mmHg). Under diazepam/alphaxalone-alphadolone and chloralose-urethane, respiration was depressed and blood gas levels deviated from normal to the extent that artificial ventilation would be necessary to maintain an adequate physiological state.

Anesthesia↗

PubMed1988

Cochlear blood flow increases after systemic hemodilution: comparison of simultaneous laser Doppler flowmetry and radioactive microsphere measurements.

Guinea pig cochlear blood flow was measured before and after systemic normovolemic hemodilution with high molecular weight dextran. Absolute determinations of blood flow (in the cochlea, brain, kidney and lung) were accomplished by use of radioactive-labeled (85Sr or 141Ce) microspheres. Relative measurements of the cochlear blood flow changes were made simultaneously by the use of a laser Doppler flowmeter. The flowmeter probe was placed on the first cochlear turn. Hemodilution to an average systemic hematocrit of 20% increased cochlear blood flow by 250% as measured with microspheres. The laser Doppler instrument significantly underestimated the actual flow increase giving an indication of 148%. Furthermore, the data, when analyzed on an individual trial basis, showed a very poor correlation between the two methods. The theoretical basis for these findings in relation to the use of the laser Doppler instrument is discussed.

Animals↗

PubMed1988

In vivo capillary diameters in the stria vascularis and spiral ligament of the guinea pig cochlea.

Blood microvessels in the membraneous lateral wall of the cochlea were examined using intravital microscopic techniques. A video analysis system made serial diameter measurements at 1 micron intervals along the length of selected vessel segments during four experimental conditions. For each vessel segment, the serial measurements were statistically converted into a single diameter estimate, such that the flow resistance in a uniform vessel of this diameter would equal the resistance of the real non-uniform vessel. Nominal vessel diameters found (spiral ligament: 9-12 micron; stria vascularis: 12-16 micron) were nearly double those reported earlier in histological observations (Axelsson, 1968). During stimulation the largest diameter change seen was a 3.7% dilation (about 0.5 micron) in response to breathing 5% CO2 in oxygen. Theoretically, this change could reduce vascular fluid resistance by 16%, nearly enough to explain the observed flow increase of 20%. No diameter changes occurred for 5% CO2 in air despite a 50% flow increase, nor for air pressure pulses applied at the tympanic membrane. Round window electrical stimulation of 50 microA also produced dilation (less than 2.5%), but higher current levels were ineffective. In general, blood flow increases seen in this study could not adequately be attributed to the small lateral wall vessel diameter increases nor systemic causes, suggesting that lateral wall blood flow in these instances is dependent on control within the modiolus.

Animals↗

PubMed1988

Masked cochlear whole-nerve response intensity functions altered by electrical stimulation of the crossed olivocochlear bundle.

Cochlear whole-nerve response (CAP) intensity functions were recorded from the guinea pig round window. The intensity functions were obtained in the presence of masking noise, with electrical stimulation of the crossed olivocochlear bundle (COCB), and the combination of masking noise and COCB stimulation. Electrical stimulation of the COCB produced the expected reduction of CAP magnitude for low- to moderate-intensity tone bursts. Masking noise produced reductions in CAP magnitude over the whole signal intensity range used in this study. The combination of electrical stimulation of the COCB with the masking noise produced CAP magnitude changes graded between reduction and enhancement dependent on signal and masker levels. In general, at low signal levels, the masked CAP magnitude is reduced compared to the masked alone condition. At high signal levels, the masked CAP is increased in magnitude. These results confirm and extend the earlier observations of Nieder and Nieder [Exp. Neurol. 28, 174-188 (1970); also, Nature 227, 184-185 (1970)].

Animals↗

PubMed1987

Sound-induced artifact in cochlear blood flow measurements using the laser Doppler flowmeter.

The laser Doppler flowmeter has been shown to give a response from the cochlea during high intensity acoustic stimulation which is not related to blood flow through the cochlea. The magnitude of this response depends upon the intensity and frequency of stimulation and the location of the probe on the cochlea. Evidence is presented that the response is derived from the vibration of cochlear tissue and/or the bony cochlear shell during acoustic stimulation.

Acoustic Stimulation↗

PubMed1987

Techniques for the observation and measurement of red blood cell velocity in vessels of the guinea pig cochlea.

Fluorescence techniques combined with intravital microscopy provide a powerful approach to the study of cochlear blood microcirculation. In the current study, fluorescein isothiocyanate conjugated to high molecular weight dextrans was added to plasma to enhance the visual contrast of flowing blood in microscopic images from the guinea pig cochlea. Photometric signals, obtained from video pictures of the blood vessels, provided a means to continuously measure red cell velocity by using crosscorrelation algorithms to extract the time delay for moving features of the image. Alternatively, a small amount of fluorescently-labeled red blood cells (RBCs) were added to the vascular volume to serve as natural indicators of whole blood flow. The speed of these cells was measured by video photometric detection of the time required for the cells to pass between two predetermined positions in the television image. RBCs can be made fluorescent by chemical bonding of a fluorochrome to the cell membrane or by internal loading of the cell with an inert fluorochrome. Labeled RBCs provide a means to determine blood velocity in capillaries having extremely poor optical contrast, a situation which is generally the case for relatively thick tissues such as the lateral wall of the membranous labyrinth.

Animals↗