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Biomedical subjects

B F Leek

Publications and source records attributed to B F Leek.

At least 19 recordsLinked to original sources

The effects of experimentally induced fever on the estimated blood flow to and oxygen utilization by the liver and the viscera drained by the portal vein in sheep.

Intrajugular injection of a purified E. coli lipopolysaccharide induced a biphasic fever in sheep after a latent period of 12 to 20 min. The changes in the blood flow from the liver and from the viscera drained by the portal vein were: (a) in the latent period, decreases in total hepatic blood flow (THF) due to decreased portal venous blood flow (PVF); (b) during the first febrile phase, increases in THF due to increased hepatic arterial blood flow and, (c) in the second febrile phase, decreases in THF due to decreased PVF. Although there were large variations in the oxygen supply to the viscera drained by the portal vein and to the liver, there were relatively small or no changes in their oxygen consumption.

Analysis of Variance

Rumination in pregnant ewes.

The daily rumination time (DRT) and the nycterohemeral pattern of rumination were recorded in six ewes before mating and during late pregnancy and in one unmated ewe. The mean DRT was shorter during pregnancy (mean: 329 min/day) than before mating (mean: 435 min/day). The DRT of the unmated ewe remained constant. The nycterohemeral pattern of rumination changed little during the trial.

Animals

The evocation of rumination in sheep by the close-arterial injection of catecholamines, cholinergic drugs, autacoids and gastrointestinal hormones into the forestomach.

The effect of alpha-2 adrenoreceptor agonists, cholinergic drugs, autacoids and some gastrointestinal hormones upon the evocation of rumination in sheep when injected by close-arterial injection into the forestomach was examined. Apart from adrenaline, noradrenaline, dopamine and xylazine only one alpha-2 agonist (BHT933) evoked rumination effectively. Acetylcholine, neostigmine, the gastrointestinal hormones and the autacoids examined did not evoke rumination consistently. Tyramine did not usually evoke rumination and guanethidine injected before adrenaline did not prevent the latter from evoking rumination. The evocation of rumination by catecholamines does not appear to involve sympathetic, cholinergic or non-sympathetic non-cholinergic neurones in the enteric nervous system to activate the nervous sensory receptors involved in the reflex evocation of rumination.

Animals

Liver blood flow and volatile fatty acid utilization in sheep before and after carbon tetrachloride treatment.

Liver blood flow and the net uptakes of acetate, propionate and butyrate were estimated in control and carbon tetrachloride (CCl4) treated sheep after an 18 h fast and during intra-ruminal infusion of a solution of the above volatile fatty acids (VFA). Portal venous blood flow was increased and the hepatic arterial blood flow reciprocally decreased by the VFA infusions in the control sheep and, even more so, in the CCl4-treated sheep. In the control sheep, increased hepatic availability of propionate was accompanied by increased hepatic uptake so that the propionate extraction percentage was maintained. In the CCl4-treated sheep, the propionate extraction percentage was greatly reduced when the propionate availability was increased and consequently the systemic blood concentrations of propionate were greatly elevated in these circumstances. Neither VFA infusion nor CCl4 treatment caused changes in hepatic acetate utilization. However, the systemic blood concentrations of acetate were significantly increased in the VFA-infused CCl4-treated sheep, suggesting changes in extra-splanchnic acetate utilization in this group. Increased hepatic butyrate availability was accompanied by increases in hepatic uptakes without changes in percentage extraction in both the control and CCl4-treated sheep.

Acetates

Dopamine-sensitive receptors that evoke rumination and modify reticulo-ruminal activity in sheep.

Dopamine (20 micrograms/kg) evoked rumination in sheep when injected as a bolus into the coeliac artery or into the left gastric artery but not when injected into the carotid artery. A mixed alpha-adrenoreceptor antagonist (phentolamine) and an alpha 2-adrenoreceptor antagonist (yohimbine) prevented dopamine from evoking rumination, but a dopaminergic antagonist (metoclopramide) did not. These findings suggest that dopamine stimulated rumination by acting upon alpha 2-adrenoreceptors situated in the area supplied by the left gastric artery, whereas dopamine injected intracerebrally may have evoked rumination by an alpha 2-adrenoreceptor effect in the central nervous system (Bueno et al., 1983) and the actions of intrajugular dopamine were exclusively upon peripheral adrenoreceptors located specifically in the gastric area. Dopamine (1 microgram/kg/min) infused into the carotid artery reduced the frequency of reticular contractions by acting upon a centrally located dopaminergic receptor mechanism sensitive to metoclopramide but not to phentolamine. When dopamine was infused into the coeliac artery or into the left gastric artery, the amplitude of reticular contractions was reduced by a peripheral mechanism sensitive both to metoclopramide and to phentolamine. Dopamine also reduced the amplitude of reticular contractions when infused into the carotid artery but to a lesser degree than when given into the coeliac or left gastric artery.

Animals

Forestomach epithelial receptor activation by rumen fluids from sheep given intraruminal infusions of volatile fatty acids.

Forty-four reticuloruminal epithelial receptors were tested with rumen fluids obtained from 12 sheep before they were intraruminally infused with 4.0M acetic acid (8 sheep) or 4.0M butyric acid (4 sheep; preinfusion rumen fluid) and with rumen fluids obtained at the onset of ruminal stasis (abolition rumen fluid). The preinfusion rumen fluids from the 8 acetic acid-infused sheep (mean pH, 6.55) contained 1.7 mM nondissociated volatile fatty acids (VFA)/L and excited none of the 25 receptors tested. Preinfusion rumen fluids from the 4 butyric acid-infused sheep (mean pH, 6.98) contained 0.3 mM nondissociated VFA/L and also did not evoke responses in any of the 19 receptors tested. Abolition rumen fluids from sheep treated with acetic acid excited 17 of the 25 receptors tested and contained 89.4 mM nondissociated VFA/L, of which nondissociated acetic acid comprised 85.0 mM/L. Abolition rumen fluids from sheep treated with butyric acid activated 14 of the 19 receptors tested and contained 61.1 mM nondissociated VFA/L, of which 38.7 mM/L was nondissociated butyric acid. Preinfusion rumen fluids whose pH values were adjusted to that of abolition rumen fluids with HCl contained nondissociated VFA levels ranging from 16.3 mM/L (acetic acid-treated sheep) to 20.6 mM/L (butyric acid-treated sheep) and elicited responses in 4 of 30 receptors tested. Preinfusion rumen fluids whose pH values were adjusted to the pH value of abolition rumen fluid with acetic acid contained 29.5 mM nondissociated VFA/L and excited 7 of 13 tested receptors.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetates

Central and local actions of opioids upon reticulo-ruminal motility in sheep.

The effects of opioids and naloxone on cyclical forestomach motility were determined in anaesthetized and conscious sheep. To assess central or peripheral opioid actions, differential routes of administration were used. Possible dynamic effects along the innervating vagovagal reflex arc were investigated electrophysiologically at the cervical level of the vagus nerve. Further, direct influences on the smooth muscle were evaluated in vitro on isolated longitudinal reticular strips. Additionally, the effects of some spasmogenic agents were studied for comparative purposes. In anaesthetized sheep, opioids depressed in an identical manner both the amplitude of spontaneous cyclical contractions and contractions evoked by electrical stimulation of the distal end of the cut cervical vagus. In conscious sheep, low doses of normorphine and loperamide inhibited frequency and amplitude centrally (20 micrograms/kg and 4 micrograms/kg via carotid artery respectively), whereas locally higher dose levels (200 micrograms/kg and 10 micrograms/kg via coeliac artery respectively) affected only the amplitude of cyclical contractions. Furthermore the opioid peptides Leu-, Met-enkephalin and [D-Ala2-Met5]-enkephalinamide preferentially depressed the amplitude of cyclical motility most efficiently if administrated via the coeliac artery. These results indicate the presence both of a central opioid action depressing frequency and amplitude and of a local opioid action depressing only the amplitude of cyclical reticulo-ruminal motility. Opioids did not alter the resting discharge of afferent tension units and similarly failed to modulate tone of reticular strips in vitro, suggesting that the opioids act locally on the intramural neuronal plexus, possibly by diminishing the output of excitatory transmitter. Whether substance P could play a role as a vagal excitatory transmitter besides the classically implicated acetylcholine has been discussed. The central opioid mechanism is probably not situated within the gastric centres but elsewhere in the brain. Naloxone (greater than or equal to 100 micrograms/kg, jugular vein) stimulated the frequency of cyclical ruminal motility only in well-defined experimental conditions, probably via a central mechanism.

Animals

Central projections of gastric afferent vagal inputs.

1. The medulla oblongata of thirteen halothane-anaesthetized, decerebellate sheep was explored systematically with recording micro-electrodes.2. The nervous activity recorded was designated either ;cyclical', if it was related to the periodic vagal outflow responsible for primary cycle movements of the reticulo-rumen, or ;afferent-like', if it was directly related to mechanical stimulation of the reticulum or the abomasum.3. Forms of mechanical stimulation were used which were known (from earlier ;single afferent fibre' studies) to evoke characteristic and distinguishable responses from four receptor types, i.e. reticular tension receptors, reticular epithelial receptors, abomasal tension receptors and abomasal mucosal receptors.4. Micro-electrode penetrations were made within a zone 4 mm lateral to the mid line, 6 mm rostral to and 2.5 mm caudal to the obex. In certain regions, ;afferent-like activity' was recorded, which corresponded to the discharge properties of one or more of the above receptor types.5. Units were sometimes excited or inhibited by more than one kind of receptor excitation, thus demonstrating the possibilities of a convergence of afferent projections and either a direct or a reciprocal relationship between receptor activity and central nervous ;afferent-like activity'.6. It is concluded that most, if not all, of the ;afferent-like activity' was recorded from the vicinity of interneurones.7. There was a partially overlapping viscerotopic organization of ;afferent-like activity' derived from abomasal and from reticular receptors.8. Regions showing ;afferent-like activity' were located dorso-laterally to regions showing ;cyclical activity' although there was some overlap between the two regions.9. ;Afferent-like activity' was recorded from regions which included the dorso-lateral part of the dorsal vagal motor nucleus, the adjacent reticular formation and the nucleus of the solitary tract between transverse planes 3 mm rostral to the obex and 1 mm caudal to the obex.10. Some of the gastric afferent vagal inputs were projected to contralateral locations via unidentified commissural connexions.

Abomasum

The effects of peripheral and central nervous influences on gastric centre neuronal activity in sheep.

1. Responses of identified vagal reticulo-ruminal motoneurones and gastric centre interneurones to changes in vagal afferent activity were examined in anaesthetized, decerebellate sheep.2. Procedures which reflexly modified the form of forestomach movements caused corresponding changes in the activities of motoneurones and Type A interneurones, whereas the activity patterns of Type B, and many Type C, interneurones were not affected.3. Distension of the pyloric region of the abomasum reduced the number of spikes in the periodic discharges of gastric centre neurones (motoneurones and Type A interneurones) with reticular activity, although the frequency of periods of activity was often increased. The afferent pathway for both effects was probably vagal.4. Unilateral vagotomy usually had little effect on the frequency and amplitude of forestomach movements, and did not influence the temporal relation between ipsilateral gastric centre discharges and the movements.5. Median division of the medulla oblongata only in the region between the gastric centres caused a loss of synchronization in the activities of the two centres, indicating the existence of commissural connexions at this level.6. Bilateral vagotomy abolished forestomach movements and motoneuronal activity, but rhythmic activity in gastric centre interneurones continued with a periodicity of approximately 1 min. This persisting periodic activity was unaffected by spinal section, but was not present after transection of the brain stem rostral to the medulla.7. Cyclical gastric centre activity could be elicited by reticular distension in preparations in which the medulla oblongata was isolated from higher regions of the brain, but, in contrast to many sheep in which the brain stem was intact, the existence of the activity was totally dependent upon peripheral afferent activity.8. The evidence indicates that medullary neurones responsible for periodic activation of vagal preganglionic reticulo-ruminal motoneurones may be excited by either or by both vagal afferent fibres from the fore-stomach or by descending, as yet unidentified, influences from the central nervous system.9. Possible roles for gastric centre interneurones in neural networks which control the periodic activation of motoneurones and which control the form of individual activity cycles are discussed.

Abomasum