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Biomedical subjects

A L Fowden

Publications and source records attributed to A L Fowden.

At least 127 records · Page 7Linked to original sources
PubMed1989

Nutritional control of respiratory and other muscular activities in relation to plasma prostaglandin E in the fetal sheep.

The effects of nutrient availability on fetal plasma prostaglandin E (PGE) concentrations, on fetal breathing movements and electromyographic (EMG) activities of fetal nuchal and forelimb muscles were investigated in pregnant ewes by varying dietary intake and by manipulation of fetal plasma glucose concentration. The incidence of fetal breathing movements (06.00-10.00 h) decreased with increasing gestational age while fetal arterial concentrations of plasma PGE increased significantly over the same period of gestation. Maternal fasting for 48 h reduced the incidence of fetal breathing movements and the amount of nuchal EMG activity (06.00-10.00 h) in animals older than 130 days but had no effect earlier in gestation. No changes in forelimb EMG activity were observed during fasting at any gestational age. Plasma PGE levels increased significantly during fasts begun both before and after 130 days of gestation. When data from fed and fasted states were combined for all fetuses, irrespective of gestational age, there was a significant inverse correlation between fetal breathing movements incidence and plasma PGE concentration in utero. This relationship was even more pronounced when the fetuses were considered individually. Insulin infusions induced hypoglycaemia, an increase in fetal plasma PGE concentration and a significant reduction in the incidence of fetal breathing movements at all ages. Glucose infusions of fetal breathing movements only after 130 days and had no effect on plasma PGE levels in utero at any gestational age. Neither insulin nor glucose infusions altered the EMG activities of the nuchal and forelimb muscles. The results show that glucose availability is an important factor in determining the incidence of fetal breathing movements in utero and indicate that nutritionally induced changes in fetal breathing movements are mediated in part by PGE. They also suggest that PGE is a physiological regulator of fetal breathing movements in the sheep during late gestation.

Animal Nutritional Physiological Phenomena↗
PubMed1988

Preferential oxygen supply to the brain and upper body in the fetal pig.

In the fetal pig over 50% of the oxgenated umbilical venous blood bypasses the liver via vascular channels of over 100mu diameter which appear to act as a ductus venosus (DV). In the present experiments the oxygen levels (pO2, SO2 and O2 content) in the fetal carotid (CA) and femoral (FA) arteries were measured to determine whether preferential streaming of the oxygenated blood is maintained from the bypass to the foramen ovale and thence through the left heart to the upper body, as in other species. The results were obtained from 12 piglets catheterized and maintained in utero under sodium pentobarbitone anaesthesia. Significant CA-FA differences in pO2, SO2 and O2 content were observed in these fetuses during both normoxaemia and hypoxaemia showing that a higher level of oxygen can be maintained to the fetal head and brain over a wide range of oxygenation. These results confirm that the hepatic channels in the fetal piglet act as a fully functional DV.

Animals↗
PubMed1988

The foramen ovale of the foetal and neonatal foal.

Hearts from 24 foals were studied; 10 were from foetuses ranging in gestational age from 230 to 322 days and 14 were from newborn and young foals aged between birth and 17 days. The foramen ovale and associated vena caval and atrial structures were examined by scanning electron microscopy. Additional observations were made by light and transmission electron microscopy. A tube-like flap of tissue was observed, extending from the aperture in the caudal vena cava to the lumen of the left atrium. In the younger foetuses, the distal end of this tube was covered with a thread-like network of tissue. In animals nearer to term, the network was replaced by distal fenestrations. Protrusions were seen on the rim of the opening of the tube as it entered the atrium. The role that these may play, together with the significance of cardiac muscle and non-elastic connective tissue in the wall of the tube, were discussed with respect to possible mechanisms of closure of the foramen ovale.

Animals↗
PubMed1988

Inhibition of 3 beta-hydroxysteroid dehydrogenase in the sow near term: effects on fetal and maternal steroids and on delivery.

The effect of Epostane, a 3 beta-hydroxysteroid dehydrogenase inhibitor, on maternal and fetal plasma progesterone and other steroids has been investigated in chronically catheterized pregnant sows near term. Epostane (1-2 mg/kg) was given i.v. and samples withdrawn from the uterine vein and artery and a fetal artery. In seven sows tested at 106-110 d gestation (term 115 d) Epostane induced parturition 25 +/- 2.1 h later with the birth of live viable young (group 1). In four sows tested with the same dose of Epostane at 106-111 d gestation parturition was not induced (group 2). A rapid drop in maternal and fetal plasma progesterone occurred after Epostane; in group 1 maternal progesterone remained below 4 ng/ml until delivery whereas in group 2 the drop was temporary, as was the decrease in fetal progesterone in all animals. Epostane also resulted in a rapid fall in maternal and fetal plasma cortisol with a gradual recovery over the following 9-12 h which was accompanied by increased ACTH (adrenocorticotrophic hormone) levels in the fetus. In group 1 fetuses a further escalation in both cortisol and ACTH occurred up to and during delivery while in group 2 basal concentrations were restored after 24 h. Epostane also reduced maternal oestrone concentrations in both groups over the 6-9 h after drug treatment. In group 2 the basal oestrone concentrations and the oestrone/progesterone ratio before and after Epostane administration were lower than in group 1 which may in part explain the failure of Epostane to induce labour in the former despite their similar gestational age. It is concluded that Epostane is not a reliable inducing agent in the sow when infused within 5-10 d of term although enhanced adrenocortical activity probably ensures the viability of the piglets if delivered.

3-Hydroxysteroid Dehydrogenases↗
PubMed1988

The effects of pancreatectomy on the rates of glucose utilization, oxidation and production in the sheep fetus.

The effects of fetal pancreatectomy on the uptake and metabolism of glucose were investigated in chronically catheterized sheep fetuses during late gestation by using tracer methodology. Rates of glucose uptake and metabolism were also measured in pancreatectomized fetuses during the infusion of insulin. Pancreatectomy produced hypoinsulinaemia and significantly reduced the rates of fetal glucose utilization and umbilical glucose uptake in comparison to intact fetuses of a similar gestational age. There was no significant alteration in the glucose oxidation fraction after pancreatectomy but because glucose utilization was low in the pancreatectomized fetuses, the rate of fetal glucose oxidation was significantly less after pancreatectomy than in intact animals. No apparent endogenous production of glucose was observed in the pancreatectomized fetuses. Insulin infusion into the pancreatectomized fetuses raised the rates of umbilical glucose uptake and of fetal glucose utilization and oxidation by 40-50% to values similar to those observed in intact animals. The endogenous production of glucose remained negligible during the infusion of insulin into the pancreatectomized fetuses. There was a net flux of radioactive glucose from the pancreatectomized fetus to the uteroplacental tissues and from the uteroplacental tissues into the uterine circulation. These net fluxes and the rate of placental metabolism of tracer glucose decreased significantly during the infusion of insulin into the pancreatectomized fetus. When all the data were combined, partial correlation analyses of the net uteroplacental uptake of tracer glucose and the fetal concentrations of plasma insulin and blood glucose showed that the fetal arterial glucose concentration was the major influence on the net flux of tracer from the fetus to the uteroplacental tissues. These observations demonstrate that the endogenous concentration of insulin has an important role in regulating glucose metabolism in sheep fetus during late gestation.

Animals↗
PubMed1987

The nutritional regulation of plasma prostaglandin E concentrations in the fetus and pregnant ewe during late gestation.

1. The effects of nutrient availability on the plasma concentrations of prostaglandin E (PGE) were investigated in chronically catheterized ewes and their fetuses during late gestation by varying dietary intake and by experimental manipulation of the fetal plasma concentration of glucose. The aim of the study was to determine whether varying the glucose level altered the fetal and maternal concentrations of plasma PGE. 2. Basal plasma concentrations of PGE increased with increasing gestational age in both the fetus and ewe. Fetal plasma concentrations of PGE were positively correlated with the corresponding uterine venous concentrations throughout the period of study. There was also a significant venous--arterial difference in plasma PGE concentration across the uterus at all gestational ages studied. 3. Withdrawal of food but not water for 48 h increased the plasma PGE concentration in all the fetuses studied irrespective of gestational age. In the pregnant ewe, the effects of fasting depended on gestational age. Before 130 days, fasting only increased the uterine venous concentration of plasma PGE, while after 130 days there were significant increases in both maternal arterial and uterine venous concentrations of plasma PGE. There was also a significant widening of the uterine venous--arterial difference in plasma PGE concentration during fasts begun after 130 days of gestation. Refeeding the fasted animals restored the plasma PGE levels to normal values within 24 h in both the fetus and ewe. 4. The normal daily feeding regime had no apparent effect on plasma PGE concentrations before 130 days of gestation. However, in animals nearer to term, there were significant reductions in plasma PGE in the fetus and uterine vein in the 3-6 h period after feeding. 5. The changes in plasma PGE levels during fasting and in response to the normal daily feeding regime were correlated to the changes in plasma glucose level observed in the fetus. The slope of the line relating the changes in the fetal concentrations of plasma PGE and glucose was significantly steeper in animals older than 130 days than earlier in gestation. 6. Fetal hypoglycaemia induced by fetal infusion of insulin increased fetal concentrations of plasma PGE without any apparent change in maternal plasma PGE values. In contrast, fetal hyperglycaemia produced by infusion of glucose into the fetus had little effect on plasma PGE levels in utero. 7. The results demonstrate that nutrient availability can influence uterine output and plasma concentrations of PGE in the fetus and pregnant ewe.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1987

Effects of inhibiting 3 beta-hydroxysteroid dehydrogenase on plasma progesterone and other steroids in the pregnant mare near term.

Epostane, a competitive inhibitor of 3 beta-HSD was administered intravenously to a pregnant mare between 292 and 330 days of gestation at doses of 1-3 mg/kg/min. Plasma progesterone concentrations fell rapidly during epostane infusion in both the artery and uterine vein and remained significantly depressed for 4-5 h after the start of infusion. The venous arterial (V-A) plasma concentration difference in progesterone across the uterus also decreased significantly in response to epostane infusion. There were no significant changes in plasma progesterone or in the V-A concentration difference in control animals infused with vehicle alone. The plasma concentration of total unconjugated oestrogens in the uterine vein was reduced after administration of epostane but remained virtually unchanged in the control experiments. Uterine venous plasma concentrations of PGFM did not change significantly in the control or epostane-treated animals. Arterial plasma cortisol levels fell initially after epostane treatment but then rose to values significantly greater than before infusion. A similar increase in arterial plasma cortisol was observed in the control animals. None of the mares delivered after epostane treatment even at the highest dose. These observations demonstrate that inhibition of 3 beta-HSD alters steroidogenesis but has little effect on the length of gestation in the pregnant mare.

3-Hydroxysteroid Dehydrogenases↗
PubMed1987

Sympathoadrenal and other responses to hypoglycaemia in the young foal.

The effects of insulin-induced hypoglycaemia on plasma catecholamines, cortisol and metabolites have been examined in newborn and 7-14-day-old foals. The fall in plasma glucose elicited by the highest dose of insulin (1.0 i.u./kg) given to the neonates was slower in onset and less severe in effect than 0.5 i.u./kg in the older foals. There was a significant inverse correlation between the concentrations of glucose and adrenaline (but not noradrenaline) in plasma once the glucose level had fallen below 2 mmol/l; the adrenergic response to hypoglycaemia was greater in the 7-14-day-old foals than in the neonates. No significant changes in glucose or catecholamines were seen after fasting alone. The adrenocortical response to hypoglycaemia was poor after birth, but significant changes occurred in the older foals with a 3-fold increase in plasma cortisol at 60 min after 0.5 i.u. insulin/kg. There were significant increases in plasma FFA after hypoglycaemia in both groups of animals, but the rise was less pronounced in the neonates. A significant positive correlation was found between plasma adrenaline and FFA values. Hypoglycaemia also resulted in a significant rise in plasma lactate and a slow fall in alpha-amino nitrogen. These findings show that hypoglycaemia in the foal is followed by stimulation of the adrenal medullary component of the sympathetic system and by activation of the adrenal cortex with a number of consequent metabolic changes. The hypoglycaemic effects of insulin were more intense and the response more rapid in the older foals than in the neonates, which exhibited some degree of insulin resistance.

Animals↗
PubMed1986

The effect of pancreatectomy on the uptake of metabolites by the sheep fetus.

The effects of fetal pancreatectomy on the uptake of oxygen, glucose and lactate by the fetus, uterus and uteroplacental tissues were investigated in chronically catheterized sheep during the last third of gestation. Pancreatectomy reduced the uptake of glucose by the fetus but had little apparent effect on glucose uptake by the uterus or uteroplacental tissues. The mean umbilical uptake of glucose by the pancreatectomized fetuses was 10.4 +/- 1.1 mumol/kg . min (n = 4) which was significantly less than the value observed in the intact fetuses (24.5 +/- 2.7 mumol/kg . min, n = 4, P less than 0.01). When all the data from the pancreatectomized and intact fetuses were combined, there was a significant positive correlation between the plasma insulin concentration in utero and the umbilical uptake of glucose (r = 0.95, n = 14, P less than 0.01). The glucose/oxygen quotient in the pancreatectomized fetuses (0.32 +/- 0.02, n = 9) was significantly less than the value observed in the intact fetuses (0.59 +/- 0.04, n = 6, P less than 0.01). There was also a significant positive correlation between the glucose/oxygen quotient and the plasma concentration of insulin in the fetus (r = 0.73, n = 59, P less than 0.01). Pancreatectomy had no significant effect on the fetal lactate/oxygen quotient or on the uptake of oxygen or lactate by any of the tissues. These observations demonstrate that the endogenous concentration of insulin is a physiological regulator of glucose uptake by the fetal tissues.

Animals↗
PubMed1986

Pancreatic alpha cell function in the fetal and newborn pig.

Plasma glucagon concentrations were measured in chronically catheterized fetal pigs during the last third of gestation and compared with the values observed in anaesthetized fetuses of similar gestational age. The mean plasma concentration of glucagon in the chronically catheterized fetuses was 10.0 +/- 1.4 (S.E.M.) pmol/l (n = 11; term = 114 +/- 2 days). Concentrations were increased after catheterization and fell to baseline values within 48 h of surgery. Arginine infusion evoked a rapid release of glucagon in chronically catheterized fetuses between 105 and 108 days of gestation; the mean maximum increment in plasma glucagon was 15.4 +/- 4.5 pmol/l (n = 5). Plasma glucagon concentrations increased with increasing gestational age in both anaesthetized and chronically catheterized fetuses. Between 95 and 110 days of gestation, glucagon levels were significantly higher in anaesthetized fetuses than in chronically catheterized animals with similar normal pH values. Catheterization and prematurity had no apparent effect on plasma glucagon levels at birth. The plasma concentrations at birth were similar to those observed in the chronically catheterized fetuses in utero provided the piglets did not become acidotic during delivery. Significantly higher plasma levels of glucagon were found in newborn piglets with acidaemia (pH less than 7.3) than in piglets with normal pH values at birth (pH greater than 7.3). When all the data from the newborn piglets were combined, there was a significant negative correlation (r = -0.79, n = 39, P less than 0.01) between blood pH and the plasma concentration of glucagon at birth. These observations demonstrate that the fetal alpha cells are functional and responsive in utero and at birth.

Animals↗
PubMed1986

Effects of pancreatectomy on the growth and metabolite concentrations of the sheep fetus.

The effects of fetal pancreatectomy on the growth and metabolism of the fetal sheep were investigated in chronically catheterized animals during the last third of gestation. Fetal pancreatectomy reduced body weight and crown-rump length at delivery near term (term 145 days). Body weight was affected more than body length so the ratio of weight to length was significantly less after pancreatectomy than in intact animals (P less than 0.05). Pancreatectomized fetuses appeared to maintain a normal growth rate for 5-10 days after surgery but thereafter showed no further significant increase in body weight. When all the data from the intact and pancreatectomized fetuses were combined, there was a significant positive correlation between the plasma insulin concentration in utero and the body weight at delivery near term. The majority of organs studied were reduced in absolute weight after pancreatectomy but only the spleen and thymus were proportionally lighter when the weights were expressed as a percentage of body weight. Brain and placental weights were similar in intact and pancreatectomized fetuses. Over the range of values observed in utero, there were significant inverse correlations between the log plasma insulin level and the mean plasma concentrations of glucose, lactate, fructose and alpha-amino-nitrogen in individual intact and pancreatectomized fetuses. Insulin infusion into pancreatectomized fetuses restored the metabolite concentrations to their normal values within 48 h of infusion. The results demonstrate that insulin has a vital role in regulating fetal growth and metabolism in utero.

Amino Acids↗
PubMed1985

The effects of cortisol on the concentration of glycogen in different tissues in the chronically catheterized fetal pig.

The effect of exogenous cortisol on glycogen deposition in a number of fetal tissues was investigated in chronically catheterized fetal pigs between 80 and 95 d of gestation (term 114 d). Intravascular infusion of cortisol for 48 h increased the fetal plasma concentration of cortisol 4-fold to a value similar to that observed in piglets near to term. After infusion of cortisol, the concentration of glycogen in the lung was lower while the levels in skeletal muscle and liver were higher than those found in unoperated fetuses. There were no detectable changes in either skin or cardiac muscle glycogen after cortisol infusion. High endogenous cortisol concentrations were observed in some of the catheterized control fetuses and in two unoperated fetuses adjacent to the site of cortisol infusion. These fetuses also had detectable changes in lung, liver and skeletal muscle glycogen. When the data from all the fetuses, whether infused, control catheterized or unoperated, were combined there was a significant positive correlation between both liver and skeletal muscle glycogen concentrations and log plasma cortisol (r = 0.70 and 0.72 respectively, P less than 0.01). Lung glycogen levels were inversely related to log plasma cortisol (r = -0.67, P less than 0.01). No relation between either cardiac or skin glycogen concentration and fetal plasma cortisol could be detected. These observations demonstrate that cortisol has a marked effect on tissue glycogen levels in the immature fetal pig and suggest that the changes in glycogen concentrations observed in the liver, lung and skeletal muscle before term may be due to the pre-partum surge in fetal cortisol.

Animals↗
PubMed1984

Studies on equine prematurity 2: Post natal adrenocortical activity in relation to plasma adrenocorticotrophic hormone and catecholamine levels in term and premature foals.

Adrenocortical and medullary function was investigated during the immediate post natal period in premature and full term foals. High plasma cortisol concentrations were characteristic of the term foals in the first 2 h after birth and these were accompanied by significant arteriovenous differences in plasma cortisol across the umbilical circulation at birth, indicating enhanced adrenal activity before delivery. No such arteriovenous differences were detected in the premature group and post natal changes in plasma cortisol were minimal. The apparent inability of the premature foal adrenal to secrete cortisol was not due to the lack of endogenous adrenocorticotrophic hormone (ACTH) because high levels of this hormone were found immediately after birth in both groups of foals. Tests on the sensitivity of the foal adrenal to exogenous ACTH1-24 (0.125 mg intramuscularly [im]) showed that a maximum response to this hormone could be elicited in term foals on the day of birth. Subsequently basal cortisol levels and the response of the adrenal to ACTH1-24 declined. By contrast, only a slight response was observed following the same dose of ACTH1-24 in the premature group. Exposure to Depot ACTH1-24 over 24 h enhanced the basal secretion of cortisol in both premature and term foals but no consistent response to the same ACTH test dose could be elicited in the former. A wide range of total plasma catecholamine concentrations was observed in both groups of newborn foals. The highest values were seen in acidotic animals and there was a significant inverse relationship between blood pH and total plasma catecholamine level at delivery.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenocorticotropic Hormone↗
PubMed1984

Studies on equine prematurity 3: Insulin secretion in the foal during the perinatal period.

The factors influencing beta cell function in the foetal and neonatal foal have been investigated in chronically catheterised foetal foals and in newborn foals delivered either spontaneously at term or by induction at different gestational ages. Insulin was detected in the foetal plasma from as early as 150 days of gestation (term = 340 days) and during the last third of gestation the foetal beta cells responded to exogenous administration of glucose and arginine and to endogenous variations in the glucose level. Insulin secretion by the foetal beta cells was depressed by anaesthesia and surgery. At birth, there was a significant positive correlation between the plasma concentrations of insulin and glucose irrespective of the maturity at birth or type of delivery (r = 0.86, n = 39, P less than 0.01). The slope of this relationship was significantly less than that relating the postoperative foetal concentration but only when delivery was difficult or prolonged was the beta cell sensitivity to glucose completely abolished. At birth, there were no significant differences in the plasma concentrations of insulin or glucose between full term foals delivered spontaneously or by induction. However, the spontaneously delivered foals showed a transient increase in the insulin concentration 15 mins after birth which was not observed in the full term foals delivered by induction. Plasma glucose concentrations were maintained during the 2 h after birth in the absence of sucking in both the induced and the spontaneously delivered full term foals. Premature foals had significantly lower plasma glucose concentrations at birth than full term foals.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗