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Biomedical subjects

W R Ferrell

Publications and source records attributed to W R Ferrell.

At least 37 records · Page 2Linked to original sources
PubMed1995

Comparison of synovial PO2 and sympathetic vasoconstrictor responses in normal and acutely inflamed rabbit knee joints.

Experiments were performed to assess the effect of acute inflammation of the rabbit knee joint on the partial pressure of oxygen in synovial fluid (Ps,O2) and nerve-mediated vasoconstrictor responses of articular blood vessels. With the hypodermic needle oxygen electrode sited within the synovial cavity in the posterior region of the knee joint, mean (+/- S.E.M.). Ps,O2 was 37.4 +/- 3.6 mmHg (n = 10) in the inflamed group, which differed significantly (P < 0.05) from that occurring in the normal group from a different series (48.2 +/- 3.1 mmHg; n = 18). Ps,O2 was found to decrease with increasing depth of penetration of the oxygen electrode into the joint cavity of the inflamed knee, as in the normal knee. The lowest values were observed close to articular cartilage. Absolute blood flow was measured using radiolabelled microspheres whilst relative changes in blood flow were assessed using laser Doppler flowmetry. The former technique showed that the inflamed joints had a significantly higher blood flow. Electrical stimulation of the posterior articular nerve (PAN) of the knee resulted in vasoconstriction of knee joint blood vessels, which was accompanied by a reduction in Ps,O2. The frequency-response and voltage-response profiles to electrical stimulation of the PAN, although differing in magnitude, showed a high degree of correlation between blood flow and Ps,O2. The frequency-response profile to electrical stimulation of the PAN shifted to the right in inflamed joints compared with normal joints, suggesting a reduction in the efficacy of the sympathetic nervous system in regulating blood flow to the inflamed joints. Although the inflamed joint had a higher blood flow, Ps,O2 was lower compared with the normal joint. The results of this study show significantly altered blood flow, Ps,O2 and nerve-mediated constrictor responses in the acutely inflamed joint. These are related to the inflammatory response and may contribute to the pathogenesis of arthritis.

Adrenergic Fibers↗
PubMed1995

Neuropeptidergic and autonomic control of the vasculature of the rat knee joint revealed by laser Doppler perfusion imaging.

An imaging technique (laser Doppler perfusion imaging, LDI), based on measurement of backscattered Doppler-broadened laser radiation, was used to provide two-dimensional images of perfusion in the exposed rat knee joint capsule. In control animals, frequency-dependent constriction of knee joint blood vessels occurred during electrical stimulation of sympathetic nerve fibres whilst dose-dependent vasodilatation of these vessels was elicited by direct application of the sensory neuropeptide substance P (SP) to the capsule. Intra-articular injection of the neurotoxic agent capsaicin did not affect vasoconstrictor responses when tested 5-7 days later, but substantially reduced dilator responses to SP. These findings indicate that capsaicin is selectively neurotoxic for sensory unmyelinated fibres but not sympathetic postganglionic fibres and is also capable of modifying receptor-mediated effects of SP. LDI is a useful method for mapping tissue perfusion, particularly in structures such as joints where the spatial distribution of blood flow is heterogeneous.

Animals↗
PubMed1995

Prolonged alteration of vasoconstrictor and vasodilator responses in rat knee joints by adjuvant monoarthritis.

Both neurogenic influences and the regulatory neuropeptide substance P (SP) have been implicated in the development of joint inflammation. Using the laser Doppler perfusion imaging technique to quantify relative changes in joint blood flow, the effects of nerve stimulation and topical SP application were examined in normal and chronically inflamed rat knee joints. Synovial inflammation was induced by unilateral intra-articular injection of Freund's complete adjuvant and experiments were carried out 1 week and 3 weeks later. Normal knees showed a frequency-dependent vasoconstriction in response to saphenous nerve stimulation over the range of 5-30 Hz and a dose-dependent vasodilation in response to SP administration. These vasoactive responses were completely abolished in the chronically inflamed knee joint, the abolition persisting throughout the investigation. Since articular cartilage is critically dependent on synovial fluid formation for its nutrition, loss of neurovascular control of the synovial microcirculation could contribute to the degenerative changes that commonly accompany chronic inflammatory joint diseases.

Animals↗
PubMed1995

A model for realism of confidence judgments: implications for underconfidence in sensory discrimination.

In a recent issue of this journal, Björkman, Justlin, and Winman (1993) presented a model of the calibration of subjective confidence judgments for sensory discrimination which they called "subjective distance theory." They proposed that there was a robust underconfidence bias in such judgments, that the model predicted such a bias, and that two different models were needed for the calibration of subjective confidence for cognitive judgments and for sensory ones. This paper addresses issues they raised. It points out that they have not presented a new model, but rather a portion of a more general one, the "decision-variable partition model" originally proposed in Ferrell and McGoey (1980). This paper explores properties of the model and shows, contrary to Björkman, Juslin, and Winman's hypotheses, that the model does not predict underconfidence, that the "hard-easy effect" can be observed with sensory discriminations, and that the model fits not only sensory, but also cognitive judgments.

Attention↗
PubMed1994

Alteration of substance P-mediated vasodilatation and sympathetic vasoconstriction in the rat knee joint by adjuvant-induced inflammation.

The effects of nerve stimulation and topical administration of substance P (SP) on the blood flow supplying the rat knee joint were measured using laser Doppler perfusion imaging. A comparison was made between the responses found in normal knees and those observed in a group of animals with unilateral chronic inflammation induced by intra-articular injection of Freund's adjuvant, 1 week prior to experimentation. In control knees, nerve stimulation produced a frequency-dependent vasoconstriction over the range of 5-30 Hz and application of SP caused a dose-dependent vasodilatation. Chronically inflamed joints showed virtually no response to either nerve stimulation or SP application, suggesting a radical alteration in sympathetic and neuropeptidergic actions.

Animals↗
PubMed1994

Plasma protein extravasation into the rat knee joint induced by calcitonin gene-related peptide.

In previous experiments, intra-articular administration of calcitonin gene-related peptide (CGRP) failed to elicit plasma protein extravasation into synovial fluid. In the present study, using a sensitive technique to assay protein in synovial fluid, intra-articular perfusion of CGRP (10(-6) M) was found to produce protein extravasation which was sustained throughout the period of infusion. Both lower (10(-7) M) and higher (10(-5) M) concentrations of CGRP failed to produce extravasation. This failure at the highest concentration of CGRP was the likely consequence of a significant fall in arterial blood pressure which occurred with administration of CGRP at this concentration. In the presence of arterial hypotension induced by an alpha-adrenoceptor antagonist, 10(-6) M CGRP failed to produce extravasation. Plasma extravasation induced by CGRP was a specific effect and not merely a consequence of its potent vasodilator properties as similar vasodilator responses induced by a beta-adrenoceptor agonist failed to induce protein leakage. These findings indicate that CGRP can alter blood vessel permeability and therefore could additionally contribute to neurally mediated inflammatory responses.

Animals↗
PubMed1994

Acute joint inflammation--mechanisms and mediators.

1. This review discusses factors contributing to acute joint inflammation, particularly sensory neuropeptides. 2. Mediators known to contribute importantly to the inflammatory process include cytokines, eicosanoids, complement and the kinin systems, histamine and 5-hydroxytryptamine and sensory neuropeptides substance P (SP) and calcitonin gene-related peptide (CGRP). 3. The pro-inflammatory neurokinins, SP and CGRP, are present in nerves innervating joints and could significantly contribute to the increased vascular permeability and hyperaemia occurring in acute arthritis. 4. Although perhaps contributing to the pathogenesis of chronic inflammatory joint disease, there is little evidence for involvement of the sympathetic nervous system in acute models of inflammation.

Acute Disease↗
PubMed1994

Impaired proprioceptive acuity at the proximal interphalangeal joint in patients with the hypermobility syndrome.

Twelve patients with the hypermobility syndrome (> or = 4 on the Beighton score) were examined to establish whether they showed any impairment of proprioception. A position matching paradigm was used which required subjects to align a finger silhouette with the kinaesthetically perceived position of their hidden index finger. Position sense at the PIP joint was found to be significantly (P < 0.0001) impaired in hypermobile patients who made larger matching errors at all angles compared to age- and sex-matched controls. The patients also demonstrated biasing in the direction of errors made when the PIP joint was positioned +/- 20 degrees away from the mid-position. These patients perceived the PIP joint to be less displaced towards the extremes of the range of movement than it really was. The mechanism underlying this impairment of proprioception remains speculative and it is not clear whether this disturbance is a cause or an effect of the hypermobility syndrome.

Adult↗
PubMed1994

Calibration of sensory and cognitive judgments: a single model for both.

In a recent issue of this journal, Winman and Juslin (34, 135-148, 1993) present a model of the calibration of subjective probability judgments for sensory discrimination tasks. They claim that the model predicts a pervasive underconfidence bias observed in such tasks, and present evidence from a training experiment that they interpret as supporting the notion that different models are needed to describe judgment of confidence in sensory and in cognitive tasks. The model is actually part of the more comprehensive decision variable partition model of subjective probability calibration that was originally proposed in Ferrell and McGoey (Organizational Behavior and Human Performance, 26, 32-53, 1980). The characteristics of the model are described and it is demonstrated that the model does not predict underconfidence, that it is fully compatible with the overconfidence frequently found in calibration studies with cognitive tasks, and that it well represents experimental results from such studies. It is concluded that only a single model is needed for both types of task.

Cognition↗
PubMed1994

Role of prostaglandins in regulation of blood flow and modulation of sympathetic vasoconstriction in normal and acutely inflamed rabbit knee joints.

Experiments were performed to investigate, in the normal and acutely inflamed rabbit knee joint, the role of prostaglandins in the regulation of joint blood flow, measured by laser Doppler flowmetry, as well as their modulation of sympathetic vasoconstriction. Close intra-arterial injection of prostaglandin E2 (PGE2) produced a dose-dependent vasodilatation in control joints, but the responses in inflamed joints were much smaller. Close intra-arterial infusion of indomethacin significantly increased the responses of the control joints to PGE2, but had no effect on the responsiveness of the inflamed joints. Nerve-mediated vasoconstrictor responses did not change significantly with close intra-arterial infusion of indomethacin, either in control or in inflamed joints. Indomethacin infusions decreased basal joint blood flow in the control joint significantly more than in the inflamed joint. The systemic blood pressure was elevated slightly only in the control group. The results of this study show that although prostaglandins have a role to play in regulation of basal blood flow in both normal and acutely inflamed rabbit knee joints, they do not appear to play a significant role in modulation of sympathetic vasoconstrictor responses. Prostaglandin E2 receptors are functional in normal knee joint blood vessels, but they may be disabled by the process of inflammation.

Animals↗
PubMed1994

Excitation of soleus/gastrocnemius gamma-motoneurones by group II knee joint afferents is suppressed by group IV joint afferents in the decerebrate, spinalized cat.

Electrical stimulation sufficient to excite group II/III afferent fibres in the posterior articular nerve (PAN) of the cat knee joint facilitated gamma-motoneurone firing in filaments of the lateral gastrocnemius/soleus (LGS) nerve. Repetitive (0.5-2.0 Hz) electrical stimulation of the PAN, produced a short latency increase of gamma-motoneurone firing with a latency ranging from 8 to 35 ms. The shortest of these delays suggests a segmental link between group II knee joint afferents and lateral gastrocnemius/soleus gamma-motoneurones. This facilitation was diminished or abolished if the first stimulus was preceded by a conditioning stimulus which excited the group IV afferents in the PAN. This depression of facilitation was dependent on the interval between the test and conditioning stimuli and the interval which produced the greatest depression was consistent with the effect being due to group IV afferents. Inhibition of the facilitation did not significantly alter the on-going discharge rate of the gamma-motoneurones. This suggests that it was not due to direct inhibition of the motoneurones.

Animals↗
PubMed1993

Acute inflammation in the rat knee joint attenuates sympathetic vasoconstriction but enhances neuropeptide-mediated vasodilatation assessed by laser Doppler perfusion imaging.

The effect of sympathetic nerve stimulation and topical application of substance P and calcitonin gene-related peptide on the blood flow of the exposed rat knee joint capsule was investigated. The responses of normal animals were compared to those of animals with acutely inflamed joints induced by intra-articular injection of 2% carrageenan. Laser Doppler perfusion imaging was used to examine the spatial distribution of blood flow in the knee joint capsule. Animals with acute joint inflammation showed markedly reduced vasoconstrictor responses to sympathetic nerve stimulation, but enhanced vasodilator responses to both substance P and calcitonin gene-related peptide when compared to normal. Prior application of either substance P or calcitonin gene-related peptide to the normal joint attenuated sympathetic vasoconstrictor responses. In the acutely inflamed knee, sympathetic vasoconstriction was replaced by a vasodilator response in the presence of neuropeptides. The reduced effectiveness of sympathetically mediated vasoconstriction and enhanced responsiveness to substance P and calcitonin gene-related peptide could contribute to the hyperaemia characteristic of inflamed joints.

Animals↗
PubMed1993

Effects of interactions of naturally-occurring neuropeptides on blood flow in the rat knee joint.

1. Changes of blood flow in the rat knee joint, measured by laser Doppler flowmetry, were produced by topical application of naturally-occurring neuropeptides to the joint capsule. 2. Substance P (SP), neurokinin A (NKA), and neurokinin B (NKB) all produced dose-dependent transient vasodilatation of the rat knee joint microvasculature. NKB showed significantly smaller vasodilator responses compared to SP and NKA which were similar in their potencies. 3. Calcitonin gene-related peptide (CGRP) produced dose-dependent vasodilatation which was more pronounced than that produced by the neurokinins. The rank order of potency was: CGRP > SP = NKA > NKB. The vasodilator effect of CGRP was also more prolonged and this extended phase was abolished by co-administration of SP. 4. Cross-tachyphylaxis was not observed with the different neurokinins, but SP and NKA showed novel antagonistic effects on NKB-induced vasodilatation. 5. Co-administration of 1 nmol of the specific NK1 receptor antagonist, CP-96345, with 1 nmol of each of the neurokinins produced significant inhibition of the vasodilator response to SP but did not affect vasodilator responses to NKA and NKB. Co-administration of CP-96345 with the neurokinins plus superfusion of the rat knee joint with a solution containing 0.1 mM CP-96345 further reduced the vasodilator responses to SP but again the vasodilator responses to NKA and NKB were not significantly altered. 6. The results suggest that multiple neurokinin receptor types may be present in the rat knee joint which could mediate the vasodilator responses of the different neurokinins. Co-release of neuropeptides from sensory nerve endings in the rat knee joint may have inter-regulatory actions on their individual responses on the microvasculature.

Animals↗
PubMed1993

Sympathetic innervation and alpha-adrenoceptor profile of blood vessels in the posterior region of the rabbit knee joint.

1. Experiments were performed to determine the nature of adrenoceptors mediating neurally-induced vasoconstriction of blood vessels in the posterior region of the rabbit knee joint capsule. 2. Electrical stimulation of the posterior articular nerve resulted in frequency-dependent vasoconstriction which was maximal at 10 Hz. This response was mediated predominantly by alpha 2-adrenoceptors as it was only slightly reduced by prazosin administration and was not only abolished but converted into a dilator response by the alpha 2-adrenoceptor antagonist rauwolscine. Further experiments with another specific alpha 1-adrenoceptor antagonist YM-12617 showed that the frequency-response curve in the presence of this antagonist did not differ significantly from control. 3. Neurally-induced vasoconstriction did not appear to have a purinergic component as it was unaffected by the P2x-purinoceptor desensitiser alpha, beta methylene ATP. 4. The rank-order of potency of alpha-adrenoceptor agonists given as a bolus by close intra-arterial injection was: adrenaline = UK-14304 > clonidine > phenylephrine, suggesting that the vasoconstrictor effects were mediated predominantly by postjunctional alpha 2-adrenoceptors. 5. The alpha 2-adrenoceptor antagonist rauwolscine converted the constrictor response to close intra-arterial injection of adrenaline into a dilator response. The vasoconstrictor responses to UK-14304, clonidine and phenylephrine were substantially inhibited by rauwolscine. The alpha 1-adrenoceptor antagonist prazosin failed to inhibit the vasoconstrictor responses to adrenaline, clonidine and UK-14304 and resulted in enhancement of their constrictor effects. 6. The enhancement of the responses to the a, and a2 agonists by prazosin appeared to be specifically related to this agent as administration of YM-12617 did not show such enhancement. The dose-response curves to both clonidine and UK-14304 in the presence of YM-12617 did not differ significantly from control responses. Responses to phenylephrine were significantly reduced by YM-12617, indicating the presence of post-junctional a,-adrenoceptors.7. These results show almost complete reversal of the adrenoceptor profile compared to results obtained in an earlier in vitro study, where responses were mediated predominantly by ax,-adrenoceptors with a small population of postjunctional a2-adrenoceptors (Ferrell & Khoshbaten, 1989). This suggests that the differing environment in vitro may not completely reflect the conditions prevailing in vivo.

Adrenergic Fibers↗
PubMed1993

Localized neural control of blood flow in the posterior region of the knee joint in anaesthetized rabbits.

Radiolabelled microspheres were used to measure blood flow of structures in and around the rabbit knee joint and to determine the effect of electrical stimulation of the posterior articular nerve (PAN) supplying the knee. Surgical exposure of the posterior aspect of the knee joint 'capsule' and section of PAN resulted in an increase in flow restricted to this region. Electrical stimulation produced frequency-dependent reductions of blood flow in the posterior region, but no alterations occurred in the anterior region or in any other surrounding structures, suggesting that the neural supply is specific to the posterior joint capsule.

Animals↗
PubMed1993

Nitric oxide modulates sympathetic vasoconstriction and basal blood flow in normal and acutely inflamed rabbit knee joints.

Experiments were performed to investigate the role of nitric oxide (NO) in the regulation of joint blood flow and in modulating sympathetic vasoconstrictor influences in normal and acutely inflamed rabbit knees. Close intra-arterial infusion of N omega-nitro_L-arginine methyl ester (L-NAME), a NO production inhibitor, reduced basal joint blood flow, measured by laser Doppler flowmetry, by 36.4 +/- 5.1% (mean +/- S.E.M.) in normal (control) and 21.4 +/- 7.8% in carrageenan-inflamed knee joints. Mean systemic arterial blood pressure was increased by 20 +/- 3.1 and 17.9 +/- 2% in control and test animal groups respectively. Joint vascular resistance was increased by 101 +/- 19% in normal and 68.9 +/- 13.7% in carrageenan-treated animals. Vasoconstrictor responses to electrical stimulation of the posterior articular nerve (PAN) were significantly smaller in the inflamed joint compared to normal. Infusion of L-NAME for 45 min resulted in an increased vasoconstrictor response by 78% in normal and 79% in inflamed joints. Subsequent close intra-arterial infusion of L-arginine failed to return the enhanced vasoconstrictor responses induced by L-NAME to their control levels in both normal and test animal groups, but partially restored blood flow changes. In both normal and inflamed joints, vasoconstriction produced by separate intra-arterial injection of the alpha 1-agonist phenylephrine (2.5 nmol) or either of the alpha 2-agonists clonidine (250 pmol) and UK-14304 (250 pmol) was increased significantly by L-NAME infusion but not completely restored to basal values by L-arginine infusion. The control responses to all three agents did not differ significantly between normal and inflamed knees.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic alpha-Agonists↗
PubMed1993

Sympathetic innervation and beta-adrenoceptor profile of blood vessels in the posterior region of the rabbit knee joint.

Experiments were performed to investigate the presence and nature of beta-adrenoceptors in blood vessels supplying the posterior capsule of the rabbit knee joint. Electrical stimulation of the posterior articular nerve (PAN) and close intra-arterial injection of adrenaline produced vasoconstriction which reversed to vasodilatation with administration of the alpha-adrenoceptor antagonist phenoxybenzamine. In almost all animals close intra-arterial injection of the beta-adrenoceptor agonist isoprenaline resulted in vasodilatation. Injection of the more selective beta-agonists dobutamine, salbutamol and terbutaline also produced vasodilatation with a rank potency order of isoprenaline > dobutamine > salbutamol > or = terbutaline. The beta-adrenoceptor antagonist propranolol abolished the dilator responses to adrenaline and isoprenaline, and significantly reduced the dilator responses to PAN stimulation in phenoxybenzamine-treated animals. Nerve-mediated vasodilatation was also reduced by the substance P antagonist D-Pro4 D-Trp7,9,10 SP4-11, suggesting that substance P contributes to this dilatation. Dobutamine, a selective beta 1-agonist, produced vasodilatation which was abolished by administration of the selective beta 1-antagonist atenolol. Isoprenaline-induced vasodilatation was substantially reduced by atenolol. The dilator response to isoprenaline appeared to be unaffected by the selective beta 2-antagonist ICI118551, but the weak dilator responses to the selective beta 2-agonists salbutamol and terbutaline were significantly reduced by this antagonist. The results of this study suggest that beta-adrenoceptors appear to be involved in the sympathetic regulation of rabbit knee joint blood flow, and that this is predominantly mediated via beta 1-adrenoceptors.

Adrenergic beta-Antagonists↗