Biomedical subjects

W S Quirk

Publications and source records attributed to W S Quirk.

At least 37 records · Page 2Linked to original sources

PubMed1996

Age-related differences in cochlear microcirculation and auditory brain stem response.

OBJECTIVE: To examine possible age-related differences in auditory sensitivity and cochlear vascular properties. DESIGN: This study is designed to provide information regarding cochlear function using physiological and audiological measures. Each animal underwent intravital microscopic evaluation of red blood cell velocity, vessel diameter, and vascular permeability in the second turn of the cochlear lateral wall. Auditory brain stem responses were used to determine hearing sensitivity. SUBJECTS: Four age ranges of male Fischer rats were studied: young, 2 to 4 months (n = 9); mid-young, 9 to 11 months (n = 8); mid-old, 18 to 20 months (n = 6); and old, 30 to 34 months (n = 10). RESULTS: Auditory brain stem response testing showed an age-related decrease in auditory sensitivity. Intravital microscopic analysis showed age-related statistically significant decreases in red blood cell velocity and increased vascular permeability with a trend for reduced capillary diameters. CONCLUSIONS: The process of aging is associated with many biochemical and physiological changes that include decrease in cellular water concentration, ionic changes, and decreased elasticity of cellular membranes. One contributing factor to this process may be altered vascular characteristics, such as reduced flow and vascular plasticity, as well as increased vascular permeability. These age-related changes may result in reductions in oxygen and nutrient delivery, and also waste elimination. Our results suggest that progressive age-associated vascular compromise may be a contributing factor in presbycusis.

Age Factors↗

PubMed1996

Dorsal cochlear nucleus blood flow during acoustic stimulation.

Dynamic in vivo changes in dorsal cochlear nucleus blood flow during pure-tone stimulation were assessed with intravital microscopy. Subjects were stimulated with 5-, 10-, or 15-kHz pure tones at 70, 80, and 90 dB sound pressure level. Measurements in red blood cell velocity and vessel diameter were made in capillaries overlying the 10-kHz isofrequency band of the dorsal cochlear nucleus. Stimulation with 10 kHz induced intensity-dependent increases in local blood flow in the 10-kHz isofrequency band of the dorsal cochlear nucleus. Stimulation with 5 kHz and 15 kHz, frequencies represented in remote locations on the dorsal cochlear nucleus surface, did not significantly alter blood flow in the defined 10-kHz isofrequency band. These data demonstrate a direct relationship between spectral and intensity-dependent pure-tone stimulation of the dorsal cochlear nucleus and increases in local blood flow. These findings suggest that tonal stimulation of the dorsal cochlear nucleus induces an increase in local metabolic demands with resultant rapid blood flow increases.

Acoustic Stimulation↗

PubMed1996

Association of mitochondrial DNA deletions and cochlear pathology: a molecular biologic tool.

The purpose of these experiments was to develop a method of isolation, amplification, and identification of cochlear mitochondrial DNA (mtDNA) from minute quantities of tissue. Additionally, studies were designed to detect mtDNA deletions (mtDNA del) from the cochlea that previously have been amplified from other organ systems and tissues. MtDNA del have been associated with many pathologies, including neurological disorders, sensorineural hearing loss, ischemia, cardiomyopathies, and aging. DNA was extracted from rat and human tissues, and polymerase chain reaction was used to amplify mtDNA sequences. A 360 base pair (bp) cytochrome-b gene product and the highly conserved ND1-16S ribosomal ribonucleic acid regions found only in mtDNA were amplified from all tissues. Preliminary studies have identified a 4834 bp mtDNA del in aged rats and a corresponding 4977 bp mtDNA del in aged humans. Additionally, preliminary results in human archival temporal bone studies reveal the presence of the 4977-bp mtDNA deletion in two out of three patients with presbycusis. The deletion was not evident in age-matched control patients without a history of presbycusis. This technique of mtDNA identification makes it possible to investigate specific mtDNA defects from a single cochlea, promoting the study of hereditary hearing loss and presbycusis at a molecular biologic level.

Aged↗

PubMed1996

Pentoxifylline maintains cochlear microcirculation and attenuates temporary threshold shifts following acoustic overstimulation.

The etiology of noise-induced hearing loss is poorly understood despite years of clinical experience and experimental investigations. One potential mechanism which may contribute to noise-induced temporary threshold shifts (TTS) are vascular pathologies in the microcirculation of the cochlea. Several studies have demonstrated histologic evidence of reduced cochlear blood flow following noise exposure. Recent studies utilizing intravital microscopy (IVM) complement these histologic studies and furthermore demonstrate localized ischemia during noise exposure. The purpose of the current study was to attempt to maintain cochlear blood flow during noise exposure by treating with pentoxifylline, a xanthine derivative which promotes blood flow in capillary beds. The possibility that preserved cochlear microcirculation with pentoxifylline treatment attenuates noise-induced TTS was also examined in this study. The results show treatment with pentoxifylline maintains cochlear microcirculation as assessed by continuous red blood cell movement through capillaries. Pentoxifylline treatment did not prevent vasoconstriction or increased permeability often observed in the cochlear microvasculature during noise. Treatment with this drug reduced noise-induced TTS.

Animals↗

PubMed1995

Atrial natriuretic peptide participates in the regulation of vestibular blood flow.

Atrial natriuretic peptide (ANP) is a cardiac hormone which exerts natriuretic, diuretic and vasorelaxant effects. Among the many organs and vascular beds populated with ANP receptors (Genest and Cantin, 1988) are the vestibular and auditory organs of the inner ear (Lamprecht and Meyer zum Gottesberge, 1988). The purpose of the current study was to assess the potential influence of ANP on vestibular blood flow in the guinea pig. The inner ear was exposed with a posterior-lateral approach medially through the mastoid cortex. The laser Doppler probe was placed adjacent to the ampulla of the posterior semicircular canal. Baseline measurements of mean blood pressure (BP), heart rate (HR) and vestibular blood flow were established. ANP dissolved in physiologic saline was infused intravenously at concentrations of 15, 150 or 300 ng/kg/min at 10 microliters/min for 30 min. Measurements were recorded during the infusion and for a recovery period of 65 min. The control group was treated equivalently and infused with 0.15 M NaCl. Baseline BP and HR for all animals were 40.1 +/- 6.67 and 190 +/- 15.7, respectively. BP, HR and vestibular blood flow remained stable during the baseline, control and recovery conditions of saline infused subjects. Infusion of ANP (15 ng/kg/min) induced a mild elevation of BP followed by a small decrease in pressure during the post-infusion period. Vestibular blood flow showed a decrease to approximately 20% below baseline during infusion and stabilized at this level during the recovery period. Infusion of higher concentrations of ANP (150 and 300 ng/kg/min) induced a similar pattern of BP change in a dose-dependent manner. Vestibular blood flow, however, evidenced significant elevations during the post-infusion periods for both concentrations. These increases (22% and 26%, for 150 and 300 ng/kg/min, respectively) were significantly different from vestibular blood flow changes in the saline and low dose groups. The HR remained stable for baseline, infusion and recovery periods for each of the ANP infused subjects. This investigation demonstrates the systemic and local effects of ANP suggest a possible role for ANP in local regulation of vestibular blood flow.

Animals↗

PubMed1995

Cochlear vascular changes in response to loud noise.

The findings of several authors suggest that alterations in cochlear vascular physiology may contribute to noise-induced hearing loss. Although the influence of noise on cochlear microcirculation is controversial, recent investigations have identified a number of microvascular alterations during noise exposure. Researchers, using intravital microscopy, a technique which offers the advantage of continuous in vivo observation of cochlear lateral wall vessels, have observed alterations in red blood cell velocity and capillary vasoconstriction within the cochlea during exposure to noise. These alterations were sufficient to induce localized periods of stasis, alterations in vascular permeability, and local ischemia. It is possible that such noise-induced vascular ischemia may result in reduced auditory sensitivity.

Animals↗

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

Noise-induced elevations of plasma endothelin (ET-3).

The endothelins (ETs) are a novel family of peptides which participate in hemodynamic homeostasis. Elevated levels of circulating ETs are evident in several stress related conditions and are associated with a variety of vascular pathophysiologies. The purpose of the current study was to test the possibility that plasma concentrations of endothelin increase following noise exposure using radioimmunoassay (RIA). No difference in plasma endothelin was detected in rats subjected to brief noise exposure (30 min of 100 dB SPL broad-band noise) compared to control animals. Statistically significant elevations in plasma endothelin (ET-3) were measured in animals exposed to prolonged noise exposure (90 min and 72 h of 100 dB SPL broad-band noise). These results suggest that hemodynamic alterations, and potential vascular pathophysiologies accompanying prolonged exposure to noise are mediated by endothelin.

Acoustic Stimulation↗

PubMed1994

Lipid peroxidation inhibitor attenuates noise-induced temporary threshold shifts.

The purpose of this study was to investigate the protective effects of U74389F (Upjohn Co. Kalamazoo, MI), a 21-aminosteroid/lipid peroxidation inhibitor, and a member of the lazaroid drug class, on temporary threshold shifts in animals exposed to prolonged noise stimulation. Animals treated with U74389F and exposed to noise showed attenuated cochlear action potential threshold (CAP) shifts and cochlear microphonic (CM) when compared to non-drug treated noise-exposed subjects. These data suggest that inhibition of FOR induced lipid peroxidation is an important mechanism in noise-induced asymptotic temporary threshold shifts.

Acoustic Stimulation↗

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

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

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

Acute effects of cocaine on cochlear function.

The effects of a single administration of cocaine on the cochlea was evaluated by measuring amplitude-intensity functions of the N1 response of the auditory nerve. Amplitude-intensity functions of the N1 response to tone-pips of 500 Hz, 1, 2, 4 and 8 kHz were obtained before and after intraperitoneal injection of either saline, 3 mg/kg or 25 mg/kg of cocaine. N1 amplitudes were decreased after the administration of cocaine and this reduction was found to be dose dependent. The influence of cocaine on cochlear blood flow (CBF) was examined in order to test the possibility that cocaine induced reductions in CBF underlie these electro-physiological changes. Corresponding decreases in cochlear blood flow after cocaine exposure were observed.

Acoustic Stimulation↗

PubMed1993

Effects of stellate ganglion stimulation on bilateral cochlear blood flow.

The effect of intraneural electrical stimulation of the stellate ganglion (SG) on bilateral cochlear blood flow (CBF) was investigated with laser-Doppler flowmetry. The SG of 15 anesthetized guinea pigs was exposed by a novel surgical approach and stimulated with a specially designed intraneural bipolar platinum-iridium electrode. Bilateral CBF was continuously monitored. Stimulation of 0.25 mA caused a detectable increase of the systemic blood pressure (BP) and a bilateral decrease of the cochlear vascular conductance (R, defined as the ratio CBF/BP). A stimulus of 0.5 mA elicited a statistically significant ipsilateral CBF (CBFi) decrease of 3.6% +/- 5.1% from the baseline and a contralateral CBF (CBFc) decrease of 3.1% +/- 5.5%. That no statistical difference was found between CBFi and CBFc indicates that a unilateral sympathetic stimulation of the SG can cause equal bilateral responses. These responses were accompanied by a significantly increased BP (8.7% +/- 5.2% of baseline) and consequently a greatly decreased R (12.2% +/- 6.5%) of the ipsilateral cochlea. Bilateral sections of the cervical sympathetic trunk below the level of the superior cervical ganglion did not alter the evoked changes in CBF, BP, and R. It is concluded that SG stimulation can decrease the conductivity of the cochlear vessels or the supplying vessels of the cochlea. Additionally, the SG nerve fibers that cause these effects do not pass through the superior cervical ganglion.

Animals↗

PubMed1993

The protective effects of allopurinol and superoxide dismutase on noise-induced cochlear damage.

Several studies have demonstrated that noise exposure may result in local vasoconstriction of cochlear vessels. The subsequent decrease in cochlear blood flow may lead to hypoxia and predispose to the formation of free oxygen radicals (FORs). If hypoxia occurs in response to noise exposure, then drugs that scavenge or block the formation of FORs should protect the cochlea from damage resulting from hypoxic or ischemic events as well as noise trauma. Rats were exposed to 60 hours of continuous broad-band noise (90 dB SPL) and treated with superoxide dismutase-polyethylene glycol (SOD-PEG), allopurinol, or a control vehicle. Exposure to noise resulted in significant threshold shifts at each frequency tested (3, 8, 12, and 18 kHz) as measured by tone burst-evoked compound action potentials and cochlear microphonics recorded from the round window. Both of these thresholds in drug-treated animals were attenuated compared with animals exposed to noise alone. These findings show that SOD-PEG and allopurinol may preserve cochlear sensitivity associated with noise exposure. This suggests that noise-induced damage to the cochlea may be related to the activity of FORs.

Action Potentials↗

PubMed1993

Effects of electrical stimulation of the superior cervical ganglion on cochlear blood flow in guinea pig.

It has been proposed that cochlear blood flow (CBF) is controlled in part by the sympathetic nervous system. In the present study the effect of electrical stimulation of the superior cervical ganglion (SCG) on CBF in guinea pigs was investigated using laser Doppler flowmetry (LDF). Animals were anesthetized with diazepam and fentanyl and the SCG was exposed. A custom-designed bipolar cuff electrode was fixed around the ganglion and 1 ms biphasic current pulses were injected at 0.15 mA to 1.5 mA, 6 Hz. Bilateral CBF was monitored, while the ganglion was stimulated for 3 or 5 min before and after the ascending sympathetic trunk and nerve branches from SCG were sectioned. Electrical stimulation of 0.5 mA caused the ipsilateral CBF (CBFi) to decrease 11.7% +/- 1.3 from the baseline (BL), while the contralateral CBF (CBFc) increased slightly due to the change in systemic blood pressure (BP). A linear relation was observed between the level of current stimulation and evoked reduction in CBF. Cervical sympathetic trunk section (between the SCG and the middle cervical ganglion) did not influence the pattern or the amplitude of CBF change in response to electrical stimulation of SCG. Sectioning the efferent fibers of the medial inferior and medial superior branch of the SCG only minimally reduced the amplitude of the CBF decrease evoked by electrical stimulation. However, sectioning the superior lateral branch abolished this decrease.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗