Biomedical subjects

J H Coote

Publications and source records attributed to J H Coote.

At least 109 records · Page 6Linked to original sources

PubMed1986

A ventromedullary relay involved in the hypothalamic and chemoreceptor activation of sympathetic postganglionic neurones to skeletal muscle, kidney and splanchnic area.

Bilateral application of glycine to the ventral surface of the medulla produces a profound hypotension during which sympathetic vasoconstrictor activity to splanchnic, renal and skeletal muscle vascular beds is reduced. The pattern of activation of sympathetic vasoconstrictor fibres to kidney and skeletal muscle, during carotid chemoreceptor activation and hypothalamic stimulation, is attenuated as tonic sympathetic activity diminishes. Functioning ventromedullary neurones are thus necessary for maintaining tonic sympathetic nerve activity, and for reflex and brain evoked patterns of sympathetic nerve activity, in the anaesthetized cat.

Animals↗

PubMed1986

Effect of acetazolamide on exercise performance and muscle mass at high altitude.

The effect of acetazolamide (Az) on exercise performance and muscle mass in acclimatised subjects at an altitude of 4846 m was assessed in 11 subjects and compared with the effect of placebo on 10 other subjects. Exercise performance at 85% maximum heart rate fell by 37% in the Az group and by 45% in controls (p less than 0.05). Weight loss was greater in the placebo group at high altitude (p less than 0.01) and this correlated with the fall in exercise performance (p less than 0.001). During the expedition anterior quadriceps muscle thickness fell by 12.9% in the control group and 8.5% in the Az group (p less than 0.001), while biceps muscle thickness fell by 8.6% in controls and 2.3% in the Az group (p less than 0.001). Measurements of skin-fold thickness indicated a loss of 18% of total body fat in the placebo group and 5% in the Az group by the end of the expedition (p less than 0.001). Calorie intakes at altitudes above 3000 m were low and similar for the two groups. The Az group had fewer symptoms of acute mountain sickness but differences between the two groups were not statistically significant. Acetazolamide is therefore useful for climbers and trekkers who are acclimatised to high altitudes. It could be most useful at extreme altitudes, where maintenance of exercise performance and muscle mass are important.

Acetazolamide↗

PubMed1985

The involvement of serotonin neurones in the inhibition of renal nerve activity during desynchronized sleep.

Numerous 5-hydroxytryptamine (5-HT)-containing cell bodies were visualized by fluorescence microscopy in the caudal brainstem rostral to the decussation of the pyramids in a region from which a desynchronized sleep-like pattern of sympathetic activity was obtained in a previous study. In unanaesthetized mid-collicular decerebrated cats recordings were made of sympathetic activity in a renal nerve. The inhibition of renal nerve activity occurring during desynchronized sleep-like state induced by physostigmine was attenuated significantly by procedures which interfered with the pathways from the 5-HT-containing neurones. Small cuts in the dorsolateral funiculus of the cervical spinal cord reduced the inhibition from 43 +/- 6% to 14.0 +/- 3%. Microinjection of 5,7-dihydroxytryptamine into cervical spinal cord reduced the serotonin content of the thoracic cord by 22.4% and attenuated the desynchronized sleep-like state inhibition of renal nerve activity by a similar amount. Depletion of serotonin with p-chlorophenylalanine significantly reduced the inhibition of renal nerve activity during the desynchronized sleep-like state, from 42.5 +/- 5% to 10.0 +/- 2.0%. It was suggested that serotonin-containing neurones are likely to be involved in the inhibition of renal nerve activity occurring during desynchronized sleep.

5,7-Dihydroxytryptamine↗

PubMed1985

Noradrenergic projections to the spinal cord and their role in cardiovascular control.

The evidence for the location of spinally projecting noradrenergic neurones in rat, rabbit, cat, monkey and birds is reviewed. It is concluded that these neurones lie in the A7, A6, A5 and A1 groups. There is a selective innervation of the autonomic nuclei of the thoracic cord running ventrolaterally in the medulla and most probably arising from A5 and to a lesser extent from A1. A contribution from A7, although likely, is not established. Electrophysiological and pharmacological studies favour a sympatho-inhibitory role for noradrenaline and other catecholamines in the spinal cord. Experiments dealing with the possible involvement of a descending noradrenergic pathway in baroreceptor inhibition at a spinal site are reviewed. It is concluded that this question is still open.

Animals↗

PubMed1984

Estimation of conduction velocity in bulbospinal excitatory pathways to sympathetic outflows in cat spinal cord.

Experiments were performed on cats to measure the conduction velocity of the bulbospinal sympatho-excitatory axons. The lateral white matter of the cervical spinal cord and regions of the medulla were systematically explored for sympatho-excitatory points whilst recording from two sympathetic preganglionic outflows simultaneously. These were chosen a suitable distance apart to give a clear difference in latency to enable precise calculation of axonal conduction velocity between the two outflows. In addition, in a few cases conduction velocity was also measured by determining the latency shift of evoked responses, resulting from moving the stimulating electrode a known distance closer to the recording site. Conduction velocities of sympatho-excitatory axons in the spinal cord determined by these two procedures lay in the range 1.6-7.9 m/s.

Animals↗

PubMed1984

Spinal and supraspinal reflex pathways of cardio-cardiac sympathetic reflexes.

In anaesthetized cats recordings were made of reflex responses recorded in the inferior cardiac nerves of one side while stimulating the inferior cardiac nerves of the opposite side. Three reflex potentials were observed: an early (about 25 ms) reflex and a later (about 60 ms) reflex due to A afferent fibre excitation and a reflex with a much longer latency (about 180 ms) due to C afferent fibre excitation. Following spinal transection at C2 only the early A reflex remained and this was augmented.

Afferent Pathways↗

PubMed1984

Propranolol vs metoprolol vs labetalol: a comparative study in essential hypertension.

In a double blind, within patient investigation of twenty-four patients (nineteen males and five females) with a mean age of 46.3 years (SD 10.9 years) with mild to moderate essential hypertension a comparison between equipotent beta-blocking doses of propranolol, metoprolol and labetalol was carried out. Blood pressure and pulse rate were measured in lying, sitting and standing positions and before, during and after isometric and dynamic exercise. Peak expiratory flow was recorded before and during dynamic exercise. All the active treatments were better than placebo in reducing blood pressure and heart rate. Comparing the effects of treatment, labetalol lowered sitting diastolic pressure significantly more than propranolol and standing diastolic pressure than both propranolol and metoprolol. Metoprolol and propranolol were more effective in reducing heart rate. Propranolol significantly reduced peak flow rate compared to labetalol. During the exercise, both isometric and dynamic, the heart rate and the blood pressure, both systolic and diastolic, of the treated patients were lower than those on placebo. There was little difference between the drugs in the influence on blood pressure, but metoprolol and propranolol were significantly more effective than labetalol in lowering the heart rate.

Adrenergic beta-Antagonists↗

PubMed1983

Identification of spinally projecting neurones in the A1 catecholamine cell group of the ventrolateral medulla.

In anaesthetized rats, neurones were found in the ventrolateral medulla that responded to antidromic stimulation of their axons in the thoracic spinal cord. These neurones were identified as being antidromic, according to various established electrophysiological criteria. A total of 44 antidromically identified neurones were found, 23 had conduction velocities below 2.0 m/s. Many (70%) had ongoing activity with a slow firing rate (0.2-5.0 Hz). Catecholamine-containing cells were visualized in this ventrolateral region using a modified Mg+-catalyzed glyoxylic acid technique and revealed multipolar, small diameter cells (17-20 microns) which were diffusely scattered (as demonstrated in previous histofluorescence studies). The Pontamine sky blue-marked recording sites of 7 units (0.3-1.1 m/s) showed close apposition to a CA-fluorescent cell whilst a further 4 (2.0-2.7 m/s) could not be correlated with the presence of a fluorescent cell. The results are discussed in the light of recent data in the rat, suggesting that the spinal cord catecholamine innervation arises from brainstem cell groups other than A1.

Animals↗

PubMed1983

Differential pattern of sympathetic outflow during upper airway stimulation with smoke.

This study investigates directly the possibility that sympathetic discharge to the heart is decreased while it is increased to other organs during upper respiratory perfusion with cigarette smoke. Blood pressure (BP), heart rate, ECG, and respiratory movements were monitored in urethane-anesthetized rabbits. Insertion of two cannulas allowed respiration of room air while passing smoke across the upper respiratory irritant receptors and out through the nares. Through a retroplural incision, the left stellate ganglion was exposed and a cardiac branch isolated. Similarly, a left renal nerve was isolated. Multiunit nerve recordings were obtained from both nerves. In four control animals, cigarette smoke (50 ml) caused apnea, bradycardia (-116 beats/min) and increased BP (33 mmHg). Activity in the renal nerve increased (248% of control [C]) and activity in the cardiac nerve was reduced (62% C). In these animals after Flaxedil and artificial respiration, nerve activity responses were still pronounced (renal, 178% C; cardiac, 66% C). In four other barodenervated animals neural responses to smoke were similar to those observed with baroreceptors intact (renal, 211% C; cardiac, 51% C). In these animals after artificial ventilation and Flaxedil, responses were not significantly changed. These results indicate that smoke stimulation causes a differential pattern of sympathetic discharge. The responses observed cannot be accounted for by secondary adjustments through arterial baroreceptors, chemoreceptors, or pulmonary stretch receptors.

Animals↗

PubMed1982

Changes in sympathetic activity to heart and blood vessels during desynchronized sleep.

In mid-collicular decerebrate cats, the activity in sympathetic nerves to the heart, kidney, gastro-intestinal tract, pelvic viscera and blood vessels of skeletal muscle was examined during periods of extensor rigidity and during desynchronized sleep-like periods (DSp) either occurring spontaneously or induced by physostigmine sulphate. During DSp the activity in sympathetic vasoconstricstor fibres to muscle increased whereas that in the other sympathetic nerves decreased. The changes were present in vagotomized and sino-aortic denervated animals as well as in paralyzed preparations. It was concluded that the differential pattern of sympathetic activity was a characteristic of the tonic stage of desynchronized sleep and originated from a site in the central nervous system independently of afferent input.

Animals↗

PubMed1982

Desynchronized sleep-like pattern of sympathetic activity elicited by electrical stimulation of sites in the brainstem.

In unanaesthetized mid-collicular decrebrate cats, paralyzed and artificially respired, recordings were made of sympathetic activity in nerves to heart (CN), to kidney (RN) and in identified vasoconstrictor nerves to skeletal muscle (SFM), whilst stimulating electrically with monopolar electrodes at various sites throughout the pons and medulla. Comparing RN and SFM, 1 of 3 patterns of response was observed at any one site: an increase in RN and SFM activity, a reduction or abolition of activity in both or a reduction or abolition of RN activity with a simultaneous facilitation of SFM activity. The latter differential pattern of sympathetic activity is characteristic of desynchronized sleep-like periods and could only be elicited from a discrete region in the mid-line of the caudal brainstem. Stimulation in this same region produced a reduction or abolition of CN as well as RN. It was suggested that neurones within the caudal part of nucleus raphe obscurus can generate a pattern of sympathetic activity similar to that occurring naturally in desynchronized sleep.

Animals↗

PubMed1982

The influence of the paraventriculo-spinal pathway, and oxytocin and vasopressin on sympathetic preganglionic neurones.

In anaesthetized rats the effect of two procedures was studied on antidromically identified sympathetic preganglionic neurones (SPN) in the second thoracic (T) segment of the spinal cord: the application of iontophoresed oxytocin and vasopressin, and bipolar electrical stimulation of the paraventricular nucleus of the hypothalamus (PVN). In the majority of cases (16/23) oxytocin inhibited SPN firing, 1/23 being excited. Vasopressin inhibited 8/14 neurones and excited 4/14. PVN stimulation inhibited SPN apparently by an action on the membrane of SPN. The possibility that oxytocin and vasopressin act as transmitters in the paraventriculo-spinal pathway, and their possible involvement in the mediation of PVN evoked inhibition of SPN activity has been discussed.

Animals↗

PubMed1982

Some characteristics of sympathetic preganglionic neurones in the rat.

In anaesthetized rats sympathetic preganglionic neurones (SPN) were identified by their antidromic response to stimulation of the ipsilateral cervical sympathetic trunk (CST). Units were recorded at a depth of 0.75-1.1 mm from the dorsal surface of the spinal cord. The majority of SPN had axonal conduction velocities less than 1 m/s. Units could be routinely held for periods of up to 1 h. Spontaneously active SPN had discharge rates within the range 0.3-8.0 Hz. Application of horseradish peroxidase (HRP) to the central cut end of the CST resulted in the labelling of neurones only on the ipsilateral side, mainly in the intermediolateral cell column (IML) and the lateral funiculus and between the first and third thoracic (T) segments.

Action Potentials↗

PubMed1982

Respiratory and circulatory control during sleep.

A survey of the literature on a large number of vertebrate animals shows that sleep is associated with profound cardiovascular and respiratory adjustments which are very similar in each species. A hypothesis is advanced that these adjustments are 'goal directed' by neural structures in the brainstem, to ensure an adequate O2 and CO2 transport to and from the brain whilst at the same time reducing energy cost. During synchronised sleep there is a vagal bradycardia leading to reduced cardiac output and a fall in blood pressure; despite this cerebral blood flow increases. During desynchronized sleep there is a tonic fall in blood pressure and heart rate resulting from a unique repatterning of sympathetic discharge, that to heart, kidney, splanchnic and pelvic vascular beds decreasing whilst that to skeletal muscle increasing; cerebral blood flow shows a further increase. This differential pattern is probably initiated by neurones located in the caudal raphe nucleus obscurus. Phasic increases in blood pressure and heart rate also occur during desynchronized sleep mainly as a consequence of increases in sympathetic activity. Ventilation decreases during synchronized sleep accompanied by an increase in partial pressure of arterial CO2, which vasodilates cerebral blood vessels, indicating that the influence of CO2 on the level of ventilation has changed. During desynchronized sleep ventilation increases and becomes very irregular but the partial pressure of O2 and CO2 in arterial blood is little changed from wakefulness. Control of respiration is shifted to a central generator which apparently is different to the automatic/metabolic one which is normally dominant during wakefulness. Reflex control of the circulation and respiration is mainly governed by peripheral chemoreceptors, the threshold of most other afferent inputs being significantly raised during sleep.

Animals↗

PubMed1981

Inhibition of sympathetic activity by stimulating in the raphe nuclei and the role of 5-hydroxytryptamine in this effect.

The possibility that the putative transmitter 5-hydroxytryptamine (5-HT) is involved in the mediation of long latency to onset raphe-spinal inhibition of sympathetic preganglionic neurones was investigated in anaesthetized cats by stimulating sites located in nucleus raphe pallidus and obscurus and recording sympathetic discharge in T3 or T10 white rami evoked either reflexively or by intraspinal stimulation at cervical level. Several putative 5-HT antagonists were administered intravenously (i.v.) or topically to the spinal cord. In 7 cats lysergic acid diethylamide (LSD) in a dose range 25-50 microgram/kg i.v. or 0.6 microgram topically, reversibly reduced the raphe spinal inhibition by 40-100%. Topical application was more effective than i.v. administration. In 5 cats stimulating within the ventromedial reticular formation at sites unlikely to involved 5-HT neurones produced a short latency to onset inhibition which was unaffected by LSD. Methysergide, cinanserin and cyproheptadine depressed sympathetic discharge in the absence of brain stimulation in cats with CNS intact and in unanaesthetized decerebrate spinal cats. The results are discussed in the light of the known actions of the putative 5-HT antagonists.

Adrenergic Fibers↗

PubMed1981

Baroreceptor inhibition of sympathetic activity at a spinal site.

In chloralose-urethane anaesthetized cats and in one unanesthetized decerebrate cat, the possibility of a baroreceptor pathway exerting an inhibitory effect directly on the sympathetic preganglionic neurone (SPN) was examined. Stimulation of excitatory points in the brain stem and spinal cord evoked responses in T3 white ramus (T3WR) which could be markedly depressed (80-100%) by raising the pressure in an isolated carotid sinus. Conditioning-testing experiments indicated that the onset of this inhibition had a long latency (100-250 msec). Responses in T3WR evoked by stimulating both 'fast' (5 m/sec) and 'slow' (2-3 m/sec) bulbospinal pathways were similarly affected by baroreceptor stimulation. This inhibition could be much reduced (40-100%) by topical application to T3 segment of phentolamine (1-2 microgram). Baroreceptor activation also caused a complete cessation of the discharge evoked by microelectrophoretic application of glutamate to single antidromically identified SPN. The data support the suggestion of a direct action on SPN of a bulbospinal baroreceptor inhibitory pathway.

Action Potentials↗

PubMed1981

The response of individual sympathetic preganglionic neurones to microelectrophoretically applied endogenous monoamines.

In anaesthetized cats the effect on antidromically identified single sympathetic preganglionic neurones (SPN) in the third thoracic segment of microelectrophoretically applied monoamines, amino acids and acetyl choline was examined. 5-Hydroxytryptamine (5-HT) creatinine sulphate and bimaleate excited a majority of SPN. A few cells were inhibited by 5-HT creatinine sulphate. These effects were observed on spontaneously active SPN (cardiac and non-cardiac type) and on silent SPN. Noradrenaline, adrenaline and dopamine inhibited all 'types' of SPN, including spontaneously active neurons, silent neurones activated by glutamate or DL-homocysteic acid and neurones synaptically activated by electrically stimulating a brain stem excitatory region. Acetyl choline had no effect on different types of SPN.

Acetylcholine↗

PubMed1981

Contribution of noradrenaline-, dopamine- and adrenaline-containing axons to the innervation of different regions of the spinal cord of the cat.

The quantitative distributions of noradrenaline (NA), dopamine (DA) and adrenaline (A) were estimated throughout the grey and white matter at various levels of the cat spinal cord (C5, T3, T10 and L2). NA levels were high at all levels of the cord (about 1000 ng/100 mg protein), being more ventrally placed at the cervical level and tending to be more medially placed at lower thoracic and lumbar levels. DA was found at much lower concentrations than NA (less than 100 ng/100 mg protein) and generally decreased in more caudal segments. There was a mediodorsal distribution throughout the cord. A levels were extremely low throughout the cord (less than 17 ng/100 mg protein), but tended to be higher in the rostral-most segments. Up to 5 days after a total transection at T3, there was accumulation of NA in the white matter regions known to contain catecholamine axon tracts. DA, however, showed a much more restricted accumulation in the white matter. The possibility of whether each catecholamine exists separately as a neurotransmitter in the cat spinal cord is discussed.

Animals↗