Biomedical subjects

W S Quirk

Publications and source records attributed to W S Quirk.

At least 55 records · Page 3Linked to original sources

PubMed1993

Betahistine-induced vascular effects in the rat cochlea.

Betahistine (BH) has been used widely to treat cochlear disorders, such as tinnitus and Meniere's disease. The mechanism of action of BH in the cochlea is assumed to be based on its histamine-like effect on H1 receptors in the cochlear vasculature, leading to an increased cochlear blood flow (CBF). Recently it has been shown that BH can strongly affect H3 heteroreceptors (a novel histamine receptor subclass) in the periphery, via an autonomic ligand. This mechanism may also contribute to the BH effects on CBF. This study was to validate BH effects in the cochlear vasculature and to investigate the possible mechanisms of action of this drug in the inner ear vasculature. We assessed the effects of BH on CBF with the laser Doppler flowmeter in 23 rats and concluded that BH affects vascular conductivity in the cochlea in a dose-dependent fashion; betahistine diffuses through the round window, but does not have access to vascular receptors or ligands once in the labyrinthine fluids; and the H1 receptors mediate the systemic and peripheral vascular effects of BH, whereas the cochlear effect involves cholinergic receptors.

Animals↗

PubMed1992

The anterior inferior cerebellar arterial network supplying the rat cochlea and its role in autoregulation of cochlear blood flow.

The sensitivity of the cochlea is dependent upon maintenance of a delicate homeostatic environment. One mechanism which participates in providing this environment is the autoregulation of cochlear blood flow. This autoregulation is ensured through the interaction of sympathetic, peptidergic and hemodynamic mechanisms. The current study demonstrates an adaptation that also participates in cochlear blood flow autoregulation. Specifically, an anterior inferior cerebellar arterial network is described and the relative contributions of each of its vessels to total cochlear blood flow is measured using laser Doppler flowmetry. The results show that each collateral vessel contributes to the blood supply of the cochlea and that reperfusion is accompanied by hyperemia. These findings suggest an adaptation that provides stable blood flow through redundancy and compensatory potential. Additionally, these observations have implications for experimental models of ischemia.

Animals↗

PubMed1992

The influence of loud sound on red blood cell velocity and blood vessel diameter in the cochlea.

Using intravital microscopy, we observed both decreases in red blood cell velocity and possible vasoconstriction in stria vascularis capillaries of the rat cochlea in response to loud sound (Quirk et al., 1991). However, our observation of vasoconstriction was subject to error in measurements from the two dimensional images obtained with our silicon intensified (SIT) camera due to the influence of focus causing image blur. The purpose of the current study was to apply an extended focus microscopy technique to obtain quantitative assessment of vessel diameter changes (Avinash et al., 1992), as well as to extend these studies to the guinea pig model. Broad-band sound stimulation at intensities of 84 dB SPL and 110 dB SPL were used. The results show that loud sound induces a sequence of changes in cochlear blood flow. Stimulation with 110 dB SPL resulted in a mean increase (maximum = 27%) in red blood cell velocity for the first 20 min of exposure followed by a gradual decrease below baseline (minimum = -12%) prior to termination of the signal. This velocity decrease and subsequent recovery were associated with significant changes in vessel diameters of selected and measured capillaries. In contrast, the 84 dB SPL stimulus caused an increase in red blood cell velocity (maximum = 20%) and vessel diameter (mean = 7.5) during the stimulation period. No recovery was observed during the 10 min observation period following sound. Several possible mechanisms responsible for these changes are discussed.

Acoustic Stimulation↗

PubMed1992

Expression of the major mammalian stress protein in the rat cochlea following transient ischemia.

The transient expression of stress proteins in cells exposed to adverse environmental conditions is thought to provide a survival advantage. In the present study, the expression of the major mammalian stress protein, Hsp72, was characterized in the rat peripheral auditory system following varying periods of unilateral cochlear ischemia and reperfusion. Western blot analysis of whole cochlear homogenates revealed Hsp72 expression after as little as 5 minutes of cochlear ischemia. Cochlear Hsp72 immunoreactivity following 10 minutes of ischemia was observed within 2 hours, remained evident through 6 hours, and decreased toward control levels by 12 hours. Preliminary immunocytochemical localization data revealed Hsp72 expression in the outer hair cells. The characterization of Hsp72 expression following transient ischemia represents the first step toward understanding the role that stress proteins have in the protection of the mammalian auditory system.

Animals↗

PubMed1992

Experimental basis for lidocaine therapy in cochlear disorders.

In order to further our basic understanding of the effects of lidocaine hydrochloride in the inner ear, cochlear potentials and blood flow (CBF) were assessed after intravenous (i.v.), anterior inferior cerebellar artery (AICA), and local round window (RW) lidocaine administrations in guinea pigs and rats. Lidocaine RW applications produced a dose dependent decrease in compound action potentials (CAP) and cochlear microphonics (CM). The sensitivity changes were more pronounced at high frequencies. These findings suggest that lidocaine has specific pharmacological action in the inner ear other than simple anesthesia of the auditory nerve. The basal turn endocochlear potentials (EP) were not altered by topical lidocaine, implicating altered organ of Corti function following local application of lidocaine. RW applications of lidocaine had no effect on CBF or systemic blood pressure (BP). I.v. infusions caused substantial reductions in BP. In the case of systemic infusions the percent changes in CBF were equal to and accountable by the BP changes. The microinfusions (50 mg/ml, 100 nl/min) through AICA produced a 30%, long lasting increase in CBF. However, neither systemic lidocaine nor AICA infusions had an effect on CAP or CM. These findings indicate that systemically given lidocaine may not cross the blood-cochlear barrier and that the cochlear electrophysiological effects due to lidocaine when given locally are partly mediated by direct influence on cochlear hair cell function; they also suggest that lidocaine-induced interference with active ion transport in the lateral wall or an influence on CBF are not contributing factors.

Action Potentials↗

PubMed1991

The influence of intra-arterial infusion of arginine vasopressin on cochlear blood flow in the rat.

Intra-arterially infused arginine vasopressin (AVP) elevated systemic blood pressure (BP) in the Sprague-Dawley rat according to a dose-response pattern while cochlear blood flow (CoBF), as measured by laser Doppler flowmetry, was elevated only at the highest dose. Skin blood flow (SBF) decreased significantly with AVP infusion. The local infusion of AVP into the anterior inferior cerebellar artery (AICA), which supplies the common cochlear artery, produced significant dose-dependent reductions in CoBF with no changes in systemic blood pressure. Pretreatment of the local cochlear supplying vessels with an AVP-specific V1 receptor antagonist attenuated subsequent AVP-induced decreases in CoBF, thereby demonstrating specificity of the response. These results suggest that CoBF is reasonably stable in response to systemic AVP infusion until blood pressure exceeds an elevation from base level of approximately +60 mm Hg. One of the mechanisms responsible for this autoregulatory response may be vasoconstriction mediated by the interaction of vasoactive peptides such as AVP and its receptors located in the vasculature of the inner ear or in the more peripheral vessels directly supplying the cochlea.

Animals↗

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

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

The protective effects of tirilated mesylate (U74006F) on ischemic and reperfusion-induced cochlear damage.

We have recently demonstrated that allopurinol, a blocker of free oxygen radical (FOR) production, and superoxide dismutase (SOD), a scavenger of FOR, protect the cochlea from damage associated with ischemia/reperfusion. The purpose of this present study was to determine if tirilated mesylate (U74006F), a potent inhibitor of lipid peroxidation, can also protect the cochlea from ischemia/reperfusion. Eleven Wistar-Kyoto rats were randomly assigned to two groups: (1) a control group (6 animals) that was exposed to 15 minutes of cochlear ischemia by clamping the anterior-inferior cerebellar artery (AICA), followed by 15 minutes of reperfusion, and (2) a drug-treated group (5 animals) that received U74006F before ischemia/reperfusion. In the control group, the tone burst-evoked compound action potential (CAP) recorded from the round window (RW) was abolished and cochlear microphonic (CM) was reduced. In contrast, the U74006F-treated animals showed post-reperfusion sensitivity in CAP, and less of a CM threshold shift. We interpret these results to indicate that U74006F lessens cochlear damage occurring as a result of ischemia/reperfusion and supports the hypothesis that FOR-induced lipid peroxidation may be partly responsible for the cochlear damage that occurs from ischemia.

Action Potentials↗

PubMed1990

Pentoxifylline increases cochlear blood flow while decreasing blood pressure in guinea pigs.

The effects of pentoxifylline on cochlear blood flow (CoBF) were investigated in anesthetized guinea pigs by laser Doppler flowmetry and intravital microscopy red blood cell velocity measurement. Intra-arterial infusion of pentoxifylline (3, 4, and 5 mg/kg/min) produced dose-dependent reductions in blood pressure, accompanied by significant elevations in CoBF that were not dose-dependent. These results are in general agreement with previous findings from our laboratory utilizing normotensive and spontaneously hypertensive rats, however, in contrast with rats, guinea pigs revealed an initial decrease in CoBF followed by an increase. Also, pentoxifylline produced relatively smaller elevations in CoBF in guinea pigs as compared with those previously reported in rats. Taken together these results support the hypothesis that pentoxifylline increases vascular perfusion by decreasing blood viscosity and increasing the plasticity of red blood cells.

Animals↗

PubMed1989

The effects of intracerebroventricularly administered angiotensin II on blood pressure and cochlear blood flow in rats and guinea pigs.

Guinea pigs and Sprague-Dawley rats were intracerebroventricularly (icv) infused with various doses of angiotensin II (AII) in order to investigate central control of and species differences in cochlear blood flow (CBF) and blood pressure (BP). The results indicated a positive dose-response relationship between icv infusions of AII for BP and CBF in members of both species. This relationship was more predictable in the guinea pig than in the rat. In addition, responses to similar AII doses between species indicated that: a) BP elevations were significantly greater in the rat than in the guinea pig, b) CBF elevations were not significantly different between the rats and guinea pigs, and c) CBF was more highly correlated with BP in the guinea pig than in the rat. These results suggest that different relationships may exist between BP and CBF in rats and guinea pigs.

Angiotensin II↗

PubMed1989

Autoregulation of cochlear blood flow in normotensive and spontaneously hypertensive rats following intracerebroventricularly mediated adjustment of blood pressure.

Previous studies in our laboratory (Quirk et al., 1988) noted significantly impaired elevations in cochlear blood flow (CoBF) during systemic infusion of the potent vasoconstrictive agent angiotensin II (AII) in the spontaneously hypertensive rat (SHR) as compared with the normotensive Wistar-Kyoto (WKY) rat, despite similar increases in systemic blood pressure. We interpreted these results to suggest that SHRs have an exaggerated autoregulatory mechanism that controls blood supply to the cochlear vessels. However, an alternative explanation for these findings concerns the potential influence of the elevated baseline blood pressure of the SHR on CoBF. Specifically, if there is an absolute threshold blood pressure that triggers an autoregulatory response in the cochlea, then the SHRs would reach that threshold sooner than normotensive animals because they begin at a baseline blood pressure that is well above that of the WKY rat. The present study addressed this possibility by pharmacologically reducing SHR blood pressure to WKY baseline blood pressure and raising WKY to SHR baselines, followed by the infusion of previously utilized doses of AII. The results are consistent with previous findings and support our interpretation of an exaggerated autoregulation of cochlear blood supplying the SHR.

Angiotensin II↗

PubMed1989

Cochlear blood flow autoregulation in Wistar-Kyoto rats.

Wistar-Kyoto rats (WKY) were intra-arterially infused with angiotensin II (AII) or phenylephrine for 10 min. Both vasoactive compounds produced an initial increase in cochlear blood flow (CoBF) as measured by laser Doppler flowmetry, followed by a slow steady return to baseline, despite sustained elevations in systemic blood pressure. These results suggest autoregulation of CoBF in the WKY rat. In a second experiment. All was infused directly into the anterior inferior cerebellar artery (AICA) which feeds the cochlear artery. Significant reductions in CoBF were noted without changes in systemic blood pressure. Pretreatment with the specific angiotensin-receptor antagonist, sarthran (Sar1, Thr8-AII), diminished subsequent AII-induced reductions in CoBF. These results indicate that AII binding to vascular receptors may induce vasoconstriction in the supplying vessels of the cochlea, and thus, the interaction of blood-borne AII and vascular angiotensin receptors may participate in the autoregulation of CoBF.

Angiotensin II↗

PubMed1988

Tachyphylaxis of dipsogenic activity to intracerebroventricular administration of angiotensins.

Repeated intracerebroventricular (i.c.v.) administration of angiotensin II (AII) and angiotensin III (AIII) induced dipsogenic tachyphylaxis in the Sprague-Dawley rat. AIII caused a rapid suppression of drinking, whereas AII showed a progressive decline of water consumption with repeated injections. Tachyphylaxis due to the repeated i.c.v. application of AII failed to abolish subsequent drinking induced by neurotensin or carbachol, suggesting that the tachyphylaxis may be specific to the angiotensinergic system. However, AII-induced tachyphylaxis caused a complete elimination of bestatin-induced drinking which was anticipated given the likelihood that this aminopeptidase B inhibitor has its dipsogenic effect by inhibiting degradation of endogenous angiotensins. Angiotensin-induced tachyphylaxis responses could not be attributed to diminished dipsogenic activity due to volemic expansion of either the cerebroventricular space or gastrointestinal tract. These results concerned with central tachyphylaxis are consistent with previous findings in the periphery and suggest that desensitization of angiotensin receptors occurs in both populations.

Angiotensin II↗

PubMed1988

Influence of aminopeptidase inhibitors on brain angiotensin metabolism and drinking in rats.

The metabolism of [125I]angiotensin II (AII, octopeptide) and [125I]angiotensin III (AIII, heptapeptide) was determined in the cerebroventricular compartment following intracerebroventricular (i.c.v.) pretreatment with artificial cerebrospinal fluid (aCSF) or the aminopeptidase B inhibitor, bestatin (BE). Microwave fixation was used to stop brain aminopeptidase activity followed by high-performance liquid chromatography methods to measure degradation. The resulting mean t 1/2 values were: aCSF/AII = 23.5 s, BE/AII = 32.0 s; aCSF/AIII = 8.2 s, BE/AIII = 16.0 s. A second experiment indicated that i.c.v. administered BE induced considerable water consumption, while amastatin (AM, an aminopeptidase A inhibitor) did not. Combined i.c.v. treatment with BE/AII or BE/AIII produced water consumptions that were equivalent with the sum of the water intakes due to independent treatments. Unexpectedly, combined treatment with AM/AII also significantly facilitated water consumption as compared with the independent treatments. These results suggest that i.c.v. BE-induced drinking is due to the extension of the half-life of endogenous AIII, and that both AM and BE facilitate drinking to i.c.v. AII and AIII by inhibiting the degradation of AII and AIII. This delay in degradation prolongs the action of AIII at central angiotensin receptors while also slowing the conversion of AII to AIII, thus providing a depot of available AII to be converted to AIII in an obligatory manner.

Aminopeptidases↗

PubMed1988

Angiotensin II-induced changes in cochlear blood flow and blood pressure in normotensive and spontaneously hypertensive rats.

Previous investigations in our laboratory have measured significant increases in the circulating levels of the potent vasoconstrictive hormone, angiotensin II (AII; 26 and 64 pg/100 microliters plasma, normal and noise exposed, respectively), during and following noise exposure in the alert rat (Wright et al., 1981). In the present study, these levels were approximated through intra-arterial infusion in the anesthetized spontaneously hypertensive rat (SHR) and normotensive Wistar-Kyoto (WKY) rat. Laser Doppler flowmeter measurements of cochlear blood flow (CBF) indicated that despite equivalent AII-induced elevations in systemic blood pressure, CBF in the SHR did not increase to the levels measured in the WKY. Pretreatment with the specific angiotensin receptor antagonist sarile, (Sar1,Ile8-AII), reduced AII-induced elevations in systemic blood pressure in members of both strains, but did not change the overall pattern of CBF. These results indicate that SHRs may have a compromised cochlear circulation that is refractory to increases in systemic blood pressure.

Angiotensin II↗

PubMed1988

The effects of pentoxifylline on cochlear blood flow in normotensive and spontaneously hypertensive rats.

Normotensive and spontaneously hypertensive rats (SHRs) were given arterial infusions of saline and pentoxifylline in doses of 1.5, 2.0, and 3.0 mg/kg/min. Blood pressure decreased in a dose related fashion with increasing doses of pentoxifylline. Cochlear blood flow, measured via laser Doppler flowmeter, increased with infusion of pentoxifylline in members of both rat strains, but to a greater extent in SHRs than in normotensive animals. The mechanism of action appears to be decreased red blood cell rigidity which allows increased penetration of red blood cells into microvessels of the cochlea.

Animals↗

PubMed1987

Heightened blood pressure and drinking responsiveness to intracerebroventricularly applied angiotensins in the spontaneously hypertensive rat.

The effects of bolus intracerebroventricular (i.c.v.) injections of angiotensin II (AII) and angiotensin III (AIII) on blood pressure and water consumption were investigated in Okamoto-Aoki spontaneously hypertensive rats (SHR), and Wistar-Kyoto (WKY) and Sprague-Dawley (SD) normotensive controls. Heightened sensitivity to i.c.v. administered AII and AIII was observed in the SHR as compared with WKY and SD strains for both pressor and drinking responses. The results are consistent with the notion that the SHR has a genetic defect that directly perturbs central angiotensinergic transmission. Two types of defects appear plausible, an alteration in the central angiotensin receptor and its associated transduction system and/or a decrease in the efficiency of signal termination. The present results are interpreted to primarily support the second possibility that a dysfunction in central aminopeptidase activity results in an extended life expectancy of angiotensin, and perhaps other peptides, that contribute to the hypersensitivity seen in the SHR.

Angiotensin II↗