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Biomedical subjects

M E Symonds

Publications and source records attributed to M E Symonds.

99 records · Page 6Linked to original sources

The interaction of the upper airway and thermo-metabolism on respiratory rhythm during non-REM sleep in the developing lamb.

This study investigates the role of metabolic rate and of vagal airway mechanisms in sustaining rhythmic breathing in the developing lamb. Fifteen lambs were prepared, at 2 days of age under fluothane anaesthesia, for sequential studies at 4, 14, 30, 45, and 55 days of age. At each age they were maintained at an ambient temperature of 5, 10, 15, 20, 25 and 30 degrees C for at least one hour before measurements were made during N-REM sleep. In 6 lambs at 4 days and in all lambs at older ages the upper airway was by-passed (by opening a tracheal window) for 10-15 minutes at each ambient temperature. Oxygen consumption was unaffected by upper airway by-pass and there were no consistent changes in mean breathing frequency or amplitude, with the exception of shifts to panting at warm ambient temperatures. Breathing pattern was unaffected by upper airway by-pass in lambs at 4 days of age, but at older ages loss of regularity of breathing frequently occurred (up to 47% of 30 days-old lambs at 25 degrees C). This was related to the fall in oxygen consumption with age and to basal values at thermoneutrality, and coincided with lower respiratory rates and increased use of expiratory laryngeal braking. Periodic breathing (and apnea) of a fixed cycle length (9.3 +/- 0.36 s) was a common feature (62%) of the observed breathing dysrhythmia. In young lambs high metabolic rate sustained high frequency rhythmic breathing which was unaffected by upper airway by-pass.(ABSTRACT TRUNCATED AT 250 WORDS)

Age Factors↗

Beta-adrenoceptors and the effect of beta-agonists on protein metabolism in ovine primary muscle cultures.

The beta-adrenergic receptors of differentiated ovine muscle cultures derived from either fetal or pre-pubertal lambs were characterized by binding of (+/-)-[3H]CGP-12177, directly to intact cells in monolayer. Fetal muscle cells contained a single class of specific and saturable binding sites which had a dissociation constant (Kd) of 0.38 x 10(-9) M and a binding capacity of 55.2 fmol/micrograms protein. beta-Adrenergic agonists competed for the specific binding sites with a typical beta 2-adrenergic specificity. Satellite muscle cells derived from pre-pubertal lambs contained two classes of binding site. The high affinity site had a Kd of 1.02 x 10(-9) M and a binding capacity of 28.4 fmol/micrograms protein and the low affinity site a Kd of 12.1 x 10(-9) M and a binding capacity of 389 fmol/micrograms protein. beta-Adrenergic agonists competed for the specific binding sites with a typical beta 1-adrenergic specificity. The beta-agonist cimaterol had no effect on either protein synthesis or degradation in fetal muscle cells. In cultures derived from satellite cells cimaterol significantly stimulated protein synthesis at concentrations of 10(-8) - 10(-7) M and at 10(-8) - 10(-6) M in the presence of serum. These effects were maintained if 10(-5) M propranolol was added to the incubation media, but were blocked by 10(-6) M isoproterenol. Propranolol and isoproterenol had no stimulatory effects on protein synthesis. Cimaterol also had no detectable effects on protein degradation or the transport of amino acids or glucose. It is concluded that although beta-adrenergic receptors are present in ovine muscle cultures they may not play a role in the anabolic effect of beta-agonists observed in cultured muscle cells.

Adrenergic beta-Agonists↗

Lipid metabolism in shorn and unshorn pregnant sheep.

The aim of the present study was to determine how the long-term metabolic adaptations to winter shearing of the pregnant ewe result in significant changes in the rates of lipid mobilization and utilization of non-esterified fatty acids (NEFA) in comparison with unshorn controls. Continuous infusions of [1-14C]palmitic acid, [2-3H]glycerol and NaH14CO3 were used to measure whole-body lipid metabolism in fed (estimated metabolizable energy (ME) intake 9.54 MJ/d) and under-fed (estimated ME intake of 3 MJ/d), shorn and unshorn sheep over the final 4 weeks of pregnancy. Whole-body carbon dioxide, estimated heat production, total NEFA entry and oxidation rates were all significantly higher in fed shorn ewes compared with unshorn controls, even though there was no difference in the arterial plasma NEFA concentration. These differences may be mediated via an increase in the plasma concentrations of thyroid hormones in shorn animals. As a result of under-feeding any significant differences in lipid metabolism between shorn and unshorn groups were removed. In all sheep the mean total NEFA entry rate as measured using [1-14C]palmitic acid was 3.4 times the value obtained using [2-3H]glycerol. It is concluded that when sheep are fed on a diet from which no more than half the required ME for late pregnancy is obtained, then lipolysis of body fat depots occurs via the incomplete breakdown of adipose tissue triglycerides. This effect is significantly greater in the fed shorn pregnant ewe which exhibits higher entry and oxidation rates of NEFA.

Adaptation, Physiological↗

The endocrine and metabolic response to feeding in the developing lamb.

Oxygen consumption (VO2), carbon dioxide production (VCO2), heart rate and the arterial plasma concentrations of glucose, non-esterified fatty acids, thyroxine (T4), 3,5,3'-tri-iodothyronine (T3), TSH, insulin, cortisol and GH were measured before and after feeding a formula milk diet to lambs aged 9, 21, 33 and 46 days. In all age groups, VO2, VCO2 and heart rate increased significantly following feeding and this effect was greatest at 9 days of age. Both VO2 and VCO2 before and after feeding decreased with age. Plasma concentrations of T3 before feeding did not change with age, but plasma T3 levels after feeding were significantly higher in lambs aged 9 days compared with 33 and 46 days. There was no effect of feeding on TSH or age on plasma TSH and T4 concentrations. In all age groups, glucose concentration increased after feeding and was paralleled by a rise in insulin concentration. At 9 and 21 days of age plasma glucose and insulin concentrations reached a plateau after the initial postprandial increase and together with a rise in respiratory quotient was indicative of a stimulation of carbohydrate oxidation. Plasma concentrations of GH increased after feeding at 21 days and older, when the mean growth rate was also stimulated by 75%. Basal metabolic rate and dietary-induced thermogenesis both decreased with age and, as a result, metabolism associated with an increase in GH levels after feeding became more efficient in terms of growth rate after 21 days. It is therefore concluded that there are major endocrine and cardiorespiratory changes in response to feeding of the young lamb which are important in stimulating and/or facilitating its growth and development.

Animal Nutritional Physiological Phenomena↗

The control of thermoregulation in the developing lamb during slow wave sleep.

This study investigates the mechanisms involved in adjusting metabolic rate in response to acute changes in ambient temperature close to thermoneutrality during postnatal development. Twelve lambs were prepared for sequential studies at 4, 14, 30, 45 and 55 days of age. During each study they were maintained at ambient temperatures of 5, 10, 15, 20, 25 and 30 degrees C for at least 1 h and until a slow wave sleep epoch was established. Eight lambs completed all studies. In these there was a significant fall in oxygen consumption with age which was independent of ambient temperature. This effect was closely related to a decrease in plasma triiodothyronine concentration that was greatest between 4- and 14-days old lambs and was not associated with a change in the plasma concentration of thyrotrophin or thyroxine. In 4-days old lambs oxygen consumption was increased at ambient temperatures of 5 and 10 degrees C by non-shivering thermogenesis, whilst in 14- and 30-days old lambs this effect was achieved by shivering. On the basis of significant changes in oxygen consumption and/or the occurrence of shivering (lower critical temperature) and panting (upper critical temperature) we have shown that there is a fall in both upper and lower critical temperature with age and a widening of the thermoneutral zone. This was associated with a decrease in the plasma cortisol concentration and heart rate as measured at thermoneutrality, whilst rectal temperature increased from 4 to 30 days of age. The other 4 lambs, 3 of which died between 7 and 17 days of age, had low plasma triiodothyronine concentrations when studied at 4 and/or 14 days of age and their oxygen consumption at thermoneutrality was significantly lower than the normal group at 14 days. Shivering thermogenesis occurred at an earlier age and control of body temperature was less effective. It is concluded that triiodothyronine has an important role in the control of metabolic rate in the developing lamb even to meet modest changes in ambient temperature, and possibly directly in survival.

Animals↗

Effect of short term intravenous infusion of noradrenaline on energy metabolism in shorn and unshorn pregnant sheep.

The effect of a three hour intravenous noradrenaline (NA) infusion, at a dose of 0.8 micrograms min-1 kg-1 bodyweight, on energy metabolism was studied in five pairs of shorn and unshorn pregnant ewes. The concentration of oxygen and carbon dioxide in blood was significantly higher in shorn animals during saline infusion, but this difference between shorn and unshorn groups was removed by NA infusion. Significant increases in the plasma concentrations of glucose, lactate, non-esterified fatty acids (NEFA), 3-hydroxybutyrate and glycerol occurred in both shorn and unshorn animals during NA infusion. There was a 48 per cent larger rise in the plasma NEFA concentration during NA infusion in the unshorn group, suggesting that the lipolytic effect of exogenous NA is greater in these animals. NA infusion had no effect on the plasma concentration of thyroid hormones in both groups of ewes, while growth hormone levels fell and cortisol increased in all animals. The plasma insulin concentration was significantly reduced during NA treatment in the unshorn group, but was unchanged in shorn animals. These results may be a consequence of sympathetic activity already being elevated in shorn ewes due to chronic exposure to an environmental temperature below the thermoneutral zone.

Animals↗

Glucose metabolism in shorn and unshorn pregnant sheep.

1. Whole-body, hind-limb and uterine tissue metabolism of glucose was studied using a combination of isotopic and arterio-venous difference techniques in shorn and unshorn pregnant sheep over the final 4 weeks of pregnancy. This was combined with the measurement of the concentrations of oxygen and carbon dioxide in arterial blood and plasma concentrations of lactate, acetate, non-esterified fatty acids, 3-hydroxybutyrate, glycerol, growth hormone (GH), insulin, glucagon, cortisol, thyroxine and 3,5,3'-triiodothyronine (T3). 2. Glucose entry rate was 28% higher in shorn ewes compared with unshorn controls, even though there was no difference in the arterial plasma concentration of glucose. This effect may have been caused by a decrease in the molar rate, insulin: glucagon (I:G), which was 40% lower in shorn ewes as a result of a significant decrease in the plasma concentration of insulin. There was no difference in the plasma concentration of cortisol or GH. 3. Blood flow across the hind-limb or uterine tissues was not significantly different between shorn and unshorn groups, neither were the net glucose uptake, glucose oxidation rate or contribution of glucose to O2 consumption across these tissues. 4. Insulin-tolerance tests performed on a separate group of shorn and unshorn ewes showed an increased sensitivity to the hypoglycaemic effects of insulin in the shorn group. 5. There was no significant difference between shorn and unshorn animals in the contribution of glucose to CO2 output or in the proportion of glucose entry rate oxidized. CO2 entry rate was 18% higher in shorn ewes compared with unshorn controls which resulted in a 26% higher estimated value for heat production. There was a 47% increase in glucose oxidation rate in shorn ewes but there was no significant difference in the proportion of total heat production which was derived from glucose. The arterial concentrations of O2 and CO2 were significantly higher in shorn ewes, which may be an indication of the higher metabolic rate in these animals. This effect may be mediated via a significant rise in plasma T3 concentration in the shorn group. 6. It is concluded that as a result of long-term cold exposure there is a significant increase in whole-body glucose entry and oxidation rates in the shorn pregnant ewe. The increase in insulin sensitivity at the same time as a decrease in plasma insulin concentration may represent a mechanism to ensure continued glucose supply to insulin-sensitive tissues while the concomitant decrease in plasma I:G stimulates hepatic gluconeogenesis.

Animals↗

The effect of shearing on the energy metabolism of the pregnant ewe.

1. Metabolizable energy (ME) intakes, heat production, non-protein respiratory quotient (NPRQ) and the plasma concentrations of glucose, non-esterified fatty acids (NEFA), 3-hydroxybutyrate, insulin, growth hormone (GH) and cortisol were measured in shorn and unshorn pregnant ewes. 2. Lamb birth-weight was 17% higher from shorn ewes despite similar ME intakes in the two groups. Shearing resulted in a significant decrease in the digestibility of dry matter and energy. 3. Both shorn and unshorn ewes were found to be in positive nitrogen balance and negative energy balance. Heat production was 28% higher in shorn ewes. This increase in heat production in the shorn group could be completely accounted for by an increase in the oxidation of fatty acids as measured using the NPRQ values. 4. Despite an apparent increase in the use of fat as an energy source there were no effects of shearing on the mean plasma concentrations of NEFA, 3-hydroxybutyrate, GH and cortisol. 5. Measurements made at 1 h intervals for 24 h indicated a tendency for the concentrations of glucose to be increased and insulin decreased in shorn ewes, particularly, between 6 and 11 h after feeding. 6. It is concluded that shearing pregnant ewes at 8 weeks before lambing results in a chronic increase in energy requirements which are met by oxidizing body fat depots. The cold stress induced by shearing may also inhibit insulin secretion resulting in increased plasma glucose concentrations. The effects of shearing on energy metabolism in the ewe are discussed in relation to the nutrient supply for the developing fetus.

Animal Feed↗