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Biomedical subjects

D H Edwards

Publications and source records attributed to D H Edwards.

At least 73 records · Page 4Linked to original sources
PubMed1989

EDRF-mediated dilatation in the rat isolated perfused kidney: a microangiographic study.

1. X-ray microangiographic techniques were used to study the influence of endothelium-derived relaxing factor (EDRF) on vasomotion in the isolated, intact, buffer-perfused kidney of the rat. The main renal (R0), segmental (R1) and interlobar (R2) arteries (control diameters ca. 600, 400 and 300 microns respectively) were studied quantitatively. 2. Inhibition of basal EDRF activity by haemoglobin (1 microM) did not elevate perfusion pressure or constrict R0, R1 and R2 in control preparations, implying a low level of spontaneous myogenic tone. In preparations preconstricted by 0.3 microM methoxamine, haemoglobin caused a further rise in perfusion pressure and amplified constrictor responses in R1 and R2 while also inducing 'paradoxical' dilatation of R0. 3. A spatially heterogeneous pattern of diameter responses (constriction of R2 and R1 with minimal dilatation of R0) was observed with two concentrations of methoxamine (0.3 microM and 3 microM). The magnitude of these responses was, however, smaller with 3 microM than 0.3 microM methoxamine, even though it increased perfusion pressure to a greater extent (88 mmHg cf. 24 mmHg). This 'paradoxical' behaviour indicates more pronounced constriction of distal arteries (which could not be resolved quantitatively) with 3 microM methoxamine. 4. In contrast to the heterogeneity of constrictor responses induced by methoxamine, the dilator action of acetylcholine was spatially homogeneous: log IC50 values calculated from the diameter changes induced in R0, R1 and R2 were similar and, moreover, equivalent to that calculated from the corresponding alterations in perfusion pressure. The fall in perfusion pressure induced by an approximately median effective concentration of acetylcholine (0.3 microM) was completely reversed by haemoglobin, consistent with the involvement of EDRF, although, reversal of the acetylcholine-induced dilatation of R0, R1 and R2 was not observed. 5. The results are consistent with the idea that constriction of distal vessels can attenuate and even directionally reverse intrinsic constrictor responses in the proximal R0, RI and R2 'feed' arteries by producing an overriding increase in 'upstream' pressure. This effect explains the paradoxical dilatation of Ro induced by haemoglobin in the presence of 0.3 microM methoxamine, the smaller magnitude of the diameter changes induced in R0, RI and R2 by 3 microM as compared to 0.3 microM methoxamine, and the failure of haemoglobin to reverse the acetylcholine-induced dilatation of R0, R1 and R2.

Acetylcholine↗
PubMed1988

Endothelium-derived relaxing factor (EDRF) and resistance vessels in an intact vascular bed: a microangiographic study of the rabbit isolated ear.

1. Microradiographic techniques have been used to show that endothelium-derived relaxing factor (EDRF), which is believed to be nitric oxide, influences vasomotor responses in small arteries and arterioles down to 25 micron in diameter in an isolated, intact, buffer-perfused ear preparation of the rabbit. Arteries down to 75 micron in diameter, i.e. the central ear artery (G0) and its first three generations of branch vessels (G1, G2 and G3) were studied quantitatively. 2. Relative constrictor responses to 1 micron 5-hydroxytryptamine (5-HT) and the combination of 1 microM 5-HT and 1 microM histamine diminished progressively from G0 to G3. Constrictor responses to 5-HT were doubled in all generations by 1 microM haemoglobin which abolishes EDRF activity. 3. Relative dilator responses to acetylcholine or to substance P in preconstricted arteries were, in contrast, equal in the different generations. Mean -log (IC50) values calculated from diameter measurements were 7.63 +/- 0.10 M and 9.80 +/- 0.11 M, respectively. These dilator responses were abolished by 1 microM haemoglobin, implying that they were EDRF-mediated. Spatial homogeneity of relative dilator responses was found also with glyceryl trinitrate (10 or 50 microM) whose activity is thought to depend on biotransformation to nitric oxide, in both the presence and the absence of haemoglobin. 4. This finding of spatial homogeneity of the diameter response to changes in EDRF activity (or to glyceryl trinitrate) implies that EDRF influences hydrodynamic resistance more in vessels where constrictor tone is high.

Acetylcholine↗
PubMed1987

Unstimulated release of endothelium derived relaxing factor is independent of mitochondrial ATP generation.

Rabbit aortic strips were used to investigate the effect of mitochondrial inhibitors on basal (unstimulated) endothelium dependent relaxation. Since haemoglobin inhibits and the cyclic GMP phosphodiesterase inhibitor, MB22948, amplifies endothelium dependent relaxation they were used to provide evidence of basal activity of endothelium derived relaxing factor (EDRF). Basal activity was not inhibited by incubation with any of three differently acting inhibitors of mitochondrial ATP generation. The mechanism underlying basal EDRF production may thus differ from that of stimulated EDRF production, which is abolished by these mitochondrial inhibitors.

Acetylcholine↗
PubMed1987

Synaptic integration in excitatory and inhibitory crayfish motoneurons.

The passive integrative properties of two crayfish abdominal motoneurons, the fast flexor inhibitor (FI) and a posterior, ipsilateral fast flexor excitor (FE), were studied electrophysiologically and through simulations with multicompartment models of their electrotonic structures. Responses of the models to simulated giant neuron input were quite similar to the motoneurons' responses to giant neuron stimulation, which suggests that differences in the electrotonic structures and the sites of synaptic input to the two cells can account in large part for differences in their responses to a common input. A full action potential created in the initial axon compartment of the FI model produced attenuated potentials in the adjacent integrating segment compartment and contralateral soma compartment. These potentials are similar in amplitude and time course to attenuated antidromic action potentials recorded in the corresponding regions of the FI neuron. A location of the spike initiation zone of the FI at the initial axon segment is consistent with this result. The responses of FI to ipsi- and contralateral inputs are different. Shock of a single abdominal second root produced a larger, faster rising excitatory postsynaptic potential in the ipsilateral FI soma than in the contralateral soma. Second root shock also caused the contralateral FI to produce an action potential either alone or before the ipsilateral FI neuron. Responses of the FI model to ipsilateral and contralateral inputs differ in the same way as the cell's responses. Inputs to the FI model that are ipsilateral to the soma compartment produce larger responses there than do contralateral inputs. Conversely, those contralateral inputs produce larger responses in the initial axon compartment than do ipsilateral inputs. This difference results from the long integrating segment that connects the soma compartment to the initial axon compartment. These results can account for the FI responses to lateralized inputs. Unlike the responses of FIs, the soma responses of contralaterally homologous FEs to ipsilateral and contralateral second root shocks were similar in waveform and amplitude, with the ipsilateral root producing the larger response. This result is consistent with theoretical results from the FE model simulations. We conclude that a smaller size, larger input resistance and shorter membrane time constant allow the FE to respond to giant neuron input before the FI, and so help to achieve the proper timing of flexor contraction and relaxation during a tailflip.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1986

Influence of endothelium on drug-induced relaxation of the rabbit aorta.

The influence of endothelium on relaxation induced by glyceryl trinitrate (GTN) and isoprenaline (I) has been studied in isolated rabbit aortic ring preparations, in the resting state and after constriction with 5-hydroxytryptamine (5HT). In resting preparations relaxant responses to GTN and I were smaller in the presence of endothelium. In preparations constricted with 5HT relaxant responses to GTN and I were conversely greater in the presence of endothelium. These paradoxical findings are discussed in relation to basal release of endothelium derived relaxant factor.

Animals↗
PubMed1986

Production of endothelium derived relaxant factor is dependent on oxidative phosphorylation and extracellular calcium.

The production (synthesis or release or both) of endothelium derived relaxant factor was studied in rabbit aortic strip preparations and an aortic-coronary artery bioassay system. Production of endothelium derived relaxant factor was rapidly inhibited by agents that inhibit mitochondrial electron transport or F1-ATPase, or which uncouple oxidative phosphorylation, but was only slowly impaired by inhibition of glycolysis. It was dependent also on the presence of extracellular calcium with a rapid on-off response time. This study shows that production of endothelium derived relaxant factor appears to be dependent on both oxidative phosphorylation and extracellular calcium.

Acetylcholine↗
PubMed1986

Haptoglobin-haemoglobin complex in human plasma inhibits endothelium dependent relaxation: evidence that endothelium derived relaxing factor acts as a local autocoid.

Endothelium dependent relaxation of isometrically mounted rabbit aortic strip preparations was rapidly inhibited by human plasma at dilutions down to 1:1000. Gel filtration and ion exchange chromatography were used to demonstrate that this inhibitory activity was present in fractions containing haptoglobin. Purified haptoglobin itself possessed no inhibitory action against endothelium dependent relaxation, but the haptoglobin-haemoglobin complex did, consistent with the documented ability of haemoglobin to inhibit this phenomenon. The concentration of haemoglobin normally bound to haptoglobin is sufficient to account for the inhibitory properties of human plasma. This suggests that endothelium derived relaxing factor exerts no downstream intravascular effect in vivo and thus that its physiological dilator role is that of a local autocoid acting on subjacent smooth muscle.

Animals↗
PubMed1985

Evidence that cyclic guanosine monophosphate (cGMP) mediates endothelium-dependent relaxation.

The mechanism of action of endothelium-derived relaxant factor (EDRF) was studied using aortic strip preparations of the rabbit and a bioassay system of a rabbit coronary artery perfused in series with an intact aorta. Methylene blue (an inhibitor of guanylate cyclase) inhibited, and 2-O-propoxyphenyl-8-azapurine-6-one (MB22948, an inhibitor of cGMP phosphodiesterase) potentiated the vascular effects of EDRF whether these were due to its basal or to stimulated release. Infusion of these agents at different sites in the bioassay indicated that they act pharmacologically at the smooth muscle level and not on release of EDRF or by chemical interaction with EDRF. The data are consistent with the hypothesis that EDRF-induced relaxation is mediated by elevation of smooth muscle cGMP levels.

Animals↗
PubMed1985

Endothelium influences coronary and aortic vasomotion by release of an unstable humoral factor.

Using an isolated perfused coronary-artery preparation, we have demonstrated the ability of endothelium inhibit markedly to vasomotion in rabbit coronary arteries. Using a bioassay system, we have shown this effect to be mediated via the release of an unstable humoral agent (t 1/2 approximately equal to 6 sec) from endothelial cells, and we have partially characterized its chemical nature.

Acetylcholine↗
PubMed1984

Ergometrine-induced arterial dilatation: an endothelium-mediated effect.

Ergometrine has generally been regarded as a vasoconstrictor and is used clinically to provoke coronary vasospasm in susceptible patients [3, 8, 9]. The ergometrine response appears however to be complex in that it can be biphasic, the constrictor response being preceded by an initial dilator response in experimental models [4]. The explanation for this is unknown, as is the underlying mechanism responsible for the clinical condition of coronary vasospasm. We have investigated this biphasic response in isolated artery preparations and shown that the dilator component is due to ergometrine-induced release of endothelium-derived relaxant factor (EDRF).

Animals↗
PubMed1984

Compartmental models of electrotonic structure and synaptic integration in an identified neurone.

A three-compartment model of the electrotonic structure of an identified motoneurone, the median gastric (m.g.) neurone of the stomatogastric ganglion of the spiny lobster (Panulirus interruptus) was constructed, based on the passive response of the cell to a step of injected current. While its structure is only remotely related to that of the cell, the model is able to predict the passive response of the cell to any wave form of injected current. The shape of the m.g. neurone provided the basis for the development of a multicompartment model of the cell from the simple compartment model. Unlike the three-compartment model, the multicompartment model has a structure that corresponds closely to that of the cell while it retains the ability to predict the passive response of the cell to any wave form of injected current. The multicompartment model was used to analyse the electrotonic structure and synaptic integration of the cell. The axon acts as a current sink, causing steady-state voltage attenuation between the tips of different dendrites and the integrating segment to range between 26 and 89%. Steady-state voltage attenuation in the distal direction is 2% or less. Synaptic inhibition of m.g. by Interneurone 1 was simulated with simultaneously activated conductance-increase synapses located on all dendritic end-compartments of the model. Inhibitory post-synaptic potential (i.p.s.p.) wave forms recorded in the cell soma were duplicated in the soma compartment when the synaptic conductance change in each of the twenty-eight end-compartments was set equal to 5 nS for 8 ms. I.p.s.p. wave forms in dendritic end-compartments were 30% larger than the soma compartment i.p.s.p., while i.p.s.p.s in the integrating segment compartment were intermediate in size. Charge from a 92 mV, 1 ms action potential in the model axon was passively conducted from axonal compartments to the soma compartment of the model, where it reproduced the attenuated, broadened voltage wave forms of action potentials recorded in the cell soma. Passive spread of charge from an axonal action potentials to terminal dendritic compartments evoked potentials there that were 30% larger and faster than the corresponding soma compartment potential.

Action Potentials↗
PubMed1984

Isolated perfused rabbit coronary artery and aortic strip preparations: the role of endothelium-derived relaxant factor.

Isolated perfused coronary arteries and aortic ring preparations of rabbits were studied, both with intact endothelium and with endothelium removed by K-rich solution and friction respectively. Constrictor dose-responses to histamine, acetylcholine, phenylephrine and 5-hydroxytryptamine (5-HT) were measured. They were greatly depressed by the presence of endothelium in coronary preparations. In aortic preparations endothelium affected dose-responses relatively little, depressing the response to acetylcholine but apparently increasing the responses to the other three agents. Acetylcholine relaxed pre-constricted coronary or aortic preparations but only when endothelium was present. This relaxation was inhibited by quinacrine or hydroquinone. Aortic preparations had resting tone which could be increased by hydroquinone if endothelium was present, suggesting continual release of endothelium-derived relaxant factor (EDRF) at rest. When allowance was made for basal EDRF activity in aortic preparations, the maximal constrictor response to acetylcholine remained lower in the presence of endothelium, consistent with acetylcholine stimulation of EDRF, but maximal constrictor responses to the other three agents were the same with and without endothelium, suggesting that the direct constrictor response overrides EDRF activity.

Acetylcholine↗
PubMed1984

Crayfish extraretinal photoreception. I. Behavioral and motorneuronal responses to abdominal illumination.

Stimulation of blinded and sighted crayfish with ventrally directed light evokes a slow tail flexion response or a tail flexion accompanied by backward walking. The response latencies and durations of sighted animals are shorter than those of blinded animals, which indicates that visual inputs can speed a response which can be released by extraretinal photoreceptors alone. Recordings from electrodes implanted in intact, freely behaving animals demonstrate that ventral illumination tonically excites abdominal postural flexor motoneurones. The motoneurone discharge occurs first in caudal segments and then spreads rostrally, as does abdominal flexion around each segmental joint. Illumination of individual abdominal ganglia (A2-A5) tonically excites a similar flexor motoneurone response in cells of the stimulated ganglion and more caudal ganglia. Swimmeret motoneurones are also tonically excited by this stimulus. These responses can be evoked in isolated abdominal nerve cords, indicating that extraretinal photoreceptors present in these ganglia activate motor circuits that are local to the abdomen. Stimulation of A6 excites the caudal photoreceptor neurones, but only excites flexor motoneurones if the abdominal ventral nerve cord is connected to the rostral part of the CNS. The motoneurones respond with repeated bursts of activity that long outlast the stimulus or the initial high-frequency burst of the caudal photoreceptor neurones. These motoneurone responses are similar to those evoked by stimulation of command fibres that also evoke backward walking (Kovac, 1974a).

Abdomen↗
PubMed1983

Response vs excitation in response-dependent and stimulus-dependent lateral inhibitory networks.

Response-dependent and stimulus-dependent lateral inhibitory networks may be distinguished by differences in their net response vs net excitation functions. It is shown that the net response of a stable, response-dependent network is a monotonically increasing function of the net excitation. By contrast, the response of a stimulus-dependent lateral inhibitory network can either increase, decrease or remain constant as the net excitation of the network is increased, depending on the relation of the inhibition to the excitation. These differences make it possible to determine that the inhibition produced by a lateral inhibitory network is stimulus-dependent if the net response of the network declines as the network excitation increases.

Animals↗
PubMed1977

A comparative study of dextran-70, warfarin and low-dose heparin for the prophylaxis of thrombo-embolism following total hip replacement.

In a randomized, controlled clinical study, dextran-70, warfarin, or low-dose heparin were administered to patients undergoing total hip replacement on one surgical unit in an attempt to prevent deep venous thrombosis and pulmonary embolism. Calf vein thrombosis was detected by the 125I-fibrinogen uptake test. None of the methods prevented calf vein thrombosis (dextran-70, 51%; warfarin, 58-6%; heparin, 52-6%). Pulmonary embolism was completely prevented in patients treated with warfarin but occurred in 4% of patients treated with dextran-70 and 15-5% of those treated with low-dose heparin. The incidence of complications of therapy was small and comparable in each group. It is suggested that calf vein thrombosis is a frequent and in itself a non-serious complication of total hip replacement surgery and that emphasis might be placed more usefully on prevention of pulmonary embolism.

Aged↗
PubMed1977

Osteochondritis dissecans patellae.

Six cases of osteochondritis dissecans patellae have been studied in five patients in an attempt to clarify the aetiology and prognosis. Assessment of the results of treatment was performed using a standard protocol. The thirty-four previous case reports in the literature are reviewed. In four of the five patients symptoms began after flexing the knee under load and three showed patellar subluxation on tangential radiographs. Thus, repetitive shearing stress on the patellar surface is thought to be an important aetiological factor. The indication for operation is a loose osteochondral fragment either wholly or partly detached from the articular surface of the patella. Vertical excision of the affected area of articular cartilage with drilling of the underlying bone gave two "good" and two "excellent" results. Healing of the drilled area and maintenance of the cartilage space was seen in radiographs of all four cases so treated. This simple method of treatment, which probably causes filling of the defect in the surface by fibrocartilage, is recommended.

Adolescent↗
PubMed1977

Arthroplasty of the hip in ankylosing spondylitis.

In fifty-six patients with ankylosing spondylitis three types of arthroplasty had been performed in ninety-nine hips. Forty-one of the patients were men and fifteen were women, their average age at operation being forty-two years. Primary pseudarthrosis produced well-satisfied patients, but only a fair result in five hips, whereas cup arthroplasty resulted in a poor outcome for eight hips, all of which needed revision. Total replacement of eighty-six hips, however, led to 73 per cent being graded as good or excellent up to ten years later. The main complications were deep infection of five hips, para-articular ossification around nine hips (six leading to bony ankylosis), and fibrous ankylosis of six hips.

Adult↗