Biomedical subjects

R Harding

Publications and source records attributed to R Harding.

At least 37 records · Page 2Linked to original sources

PubMed1990

Endocrine and fluid-balance responses to amniotic and allantoic fluid loss in sheep.

Our aim was to determine fetal and maternal endocrine and fluid-balance responses to prolonged loss of amniotic and allantoic fluids in sheep. In seven sheep, amniotic and allantoic fluids were drained [379.1 +/- 20.1 (SE) ml/day] from 107 to 135.3 +/- 0.6 days of gestation (term: 145 days). The results from these sheep were compared with those from seven control sheep. Maternal water intake, urine production, and urine osmolality were not altered by fluid drainage, nor were fetal and maternal arterial blood gases, pH, or plasma osmolalities. Fluid drainage increased amniotic, but not allantoic, fluid osmolality. Maternal plasma cortisol concentration increased with fluid drainage, but maternal plasma concentrations of prolactin and arginine vasopressin were unchanged. Fluid drainage increased prolactin concentrations in fetal plasma and amniotic fluid, but fetal plasma concentrations of cortisol (hydrocortisone), arginine vasopressin, norepinephrine, and epinephrine were unchanged. Our results show that the fetus is capable of maintaining its plasma osmolality despite prolonged loss of fluid from its amniotic and allantoic sacs and that this is associated with alterations in the production rate and the composition of amniotic fluid.

Allantoin↗

PubMed1990

Changes in lung liquid dynamics induced by prolonged fetal hypoxemia.

Our aim was to determine the effect of prolonged fetal hypoxemia, induced by reduced maternal uterine blood flow (RUBF), on fetal lung liquid secretion, flow, and volume. In chronically catheterized fetal sheep, lung liquid volume (VL) and the secretion rate of lung liquid (Vs) were measured before and after a 24-h period of either RUBF or normoxemia. Tracheal fluid flow and the incidence of fetal breathing movements (FBM) were measured before, during, and after the 24-h period. In normoxic control fetuses Vs was not significantly altered. After 24 h of RUBF, Vs was significantly (P less than 0.005) reduced compared with pre-RUBF values. During 24 h of RUBF the incidence of FBM declined initially but returned to control values after 12-16 h. In seven of eight fetuses, over the 12- to 24-h period of RUBF, large amounts of liquid (22.7-62.6 ml) were drawn into the lungs during FBM, resulting in a net movement of amniotic fluid into the lungs. During the 18- to 24-h period of RUBF, changes in the incidence of FBM were found to be significantly and positively correlated (r = 0.86, P less than 0.005) with the changes in VL that occurred over the 24-h period. Thus, prolonged RUBF can result in the inhalation of large volumes of amniotic fluid by the fetus, which could be a cause of in utero meconium aspiration.

Amniotic Fluid↗

PubMed1990

Role of lung fluid volume in growth and maturation of the fetal sheep lung.

We studied the effects of alterations in lung fluid volume on growth and maturation of the fetal lung. In a chronic fetal sheep preparation, right fetal lung volume was decreased by drainage of lung fluid while the volume of the left lung was expanded by mainstem bronchus ligation leading to lung fluid retention. After an experimental period of 25 d (from 105 to 129 d of gestation, term = 145 d), the right (deflated) lung was significantly hypoplastic and contained less DNA than the controls; 175.15 +/- 55.18 vs. 346.77 +/- 61.97 mg, respectively; P less than 0.001. In contrast, the left (expanded) lung was significantly hyperplastic and contained more DNA than the controls; 390.74 +/- 103.53 vs. 238.85 +/- 33.32 mg, respectively; P = 0.001. Biochemical indices of lung maturation, including total phospholipids, phosphatidylcholine, and disaturated phosphatidylcholine content expressed per unit of tissue DNA, were no different when comparing the hypoplastic, hyperplastic, and control lungs. These findings demonstrate that fetal lung cell multiplication is influenced by local distension with lung fluid, while the biochemical maturation of fetal lung surfactant is under systemic control.

Animals↗

PubMed1989

Conduction velocity and fibre diameter of the peroneal nerve in normal and growth retarded fetal sheep.

In this study we have examined structural and functional aspects of nerve fibre development in experimentally growth retarded fetal sheep following restriction of placental growth by carunclectomy in 5 ewes. Measurement of whole-nerve conduction velocity in the peroneal nerve showed, for the most rapidly conducting fibres, a significant slowing from the normal value of 50.3 +/- 1.8 m/s to 33.8 +/- 3.3 m/s (P less than 0.01). Histological examination of nerve sections revealed a deficit of large myelinated fibres in growth retarded fetuses which is consistent with the conduction velocity measurements.

Animals↗

PubMed1989

The effects of pentobarbitone, diazepam and alcohol on oral breathing in neonatal and mature sheep.

Our aim was to determine the effects of pharmacological sedation on oral breathing induced by nasal obstruction in chronically prepared newborn and mature sheep. Nasal obstruction (5 min) was achieved by blocking tubes temporarily fixed into the nostrils. We continuously recorded EMG activity of the diaphragm, genioglossus and digastric muscles, intrapleural pressure and percent O2 saturation in arterial blood (SaO2). Blood samples were taken intermittently and analysed for SaO2, P02, PCO2 and pH. As previously reported, nasal obstruction in lambs and ewes led to asphyxial changes in blood gases and pH; lambs were affected more than ewes. Respiratory responses to nasal obstruction were retested after administration of pentobarbitone Na (5 and 10 mg/kg), diazepam (0.2 and 0.4 mg/kg) and alcohol (nominally 0.075 and 0.11% of blood w/v). Pentobarbitone and diazepam, both of which produced sedation, delayed the onset of oral breathing and led to a greater degree of asphyxia during nasal obstruction. EMG activities in the genioglossus and digastric muscles were inhibited by the drugs, whereas the depth of inspiratory efforts was not. Alcohol had no apparent sedative effect, nor did it significantly affect responses to nasal occlusion. We conclude that sedating doses of pentobarbitone and diazepam depress the effectiveness of oral breathing when the nose is blocked, probably owing to their inhibitory effects on activation of muscles maintaining patency of an oral airway.

Airway Obstruction↗

PubMed1989

Small intestinal development in growth-retarded fetal sheep.

The functional maturity of the gastrointestinal system is essential for the survival of the neonate. The effects of reducing placental size and the ensuing fetal growth retardation on the development of the small intestine (SI) of the sheep fetus were investigated. At 140 days of gestation (term is 147 days), fetal body weight, gastrointestinal weight (from the abomasum to the rectum, i.e., the gut), SI weight, and SI length in the growth-retarded fetuses (n = 6) were significantly reduced (p less than 0.05) when compared with age- and breed-matched control fetuses. The SI weight was disproportionately reduced as a fraction of the gut weight or SI length (p less than 0.01). The proximal SI showed marked reductions in the thickness of the wall, muscularis externa, mucosa, villus height, and crypt depth (p less than 0.003). Densities of villi and crypts were also reduced (p less than 0.02). The crypt-to-villus ratio was maintained. Glycogen was accumulated basally in the villus epithelial cells, and their nuclei were located apically. These characteristics are comparable to those of much younger fetuses. In the distal SI, interanimal variation was large; however, the mean thickness of the wall, the muscularis externa, the mucosa, and the villus height were all reduced (p less than 0.05). In this region, the density of villi and crypts, the pattern of glycogen accumulation, and the position of the nuclei did not markedly differ between growth-retarded and control fetuses. Villus cell density was increased (p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1989

The role of gastrin in the development of the gastrointestinal tract in fetal sheep.

We have investigated the role of gastrin in the development of the gastrointestinal tract during the latter part of gestation in fetal sheep. We surgically removed the major source of gastrin, the gastric (abomasal) antrum, from five fetuses at 90 days of gestation. The remaining abomasum was anastomosed to the pylorus allowing unobstructed flow of luminal contents. Another five fetuses, subjected to sham-antrectomies at 90 days, served as controls. Further surgery was performed in all fetuses at 120 days for the placement of vascular catheters to permit measurement of plasma gastrin concentrations. The fetuses were infused with [3H]thymidine to study villus cell migration rates. At 135 days of gestation samples of gastric (abomasal) fundus, and proximal and distal small intestine, were processed for histology and morphometric analysis. The antrectomized fetuses had significantly lowered plasma gastrin concentrations (P less than 0.025) between 120 and 135 days. At 135 days, the mean body weight, crown-rump length, total gut weight and small intestinal weight and length were not significantly different between the two groups. Similarly, there were no significant differences between groups in the mean thicknesses of the gut wall, mucosa and muscularis externa, or in the mean villus height and crypt depth in the proximal or distal parts of the small intestine. Villus cell migration rate in the proximal and distal small intestine was not affected by antrectomy. No simple relationship could be demonstrated between any of these parameters and plasma gastrin concentration. In the antrectomized fetuses, the mean crypt density and crypt-to-villus ratio were significantly reduced in the proximal small intestine (P less than 0.05), while only the density of villi was reduced in the distal small intestine (P less than 0.05). In the antrectomized fetuses there were significant correlations between plasma gastrin and the fraction of fundic mucosa occupied by gland and pit (P less than 0.005), and between plasma gastrin concentration and villus density (P less than 0.01) and crypt-to-villus ratio (P less than 0.025) in the proximal small intestine. In the sham group these correlations were absent. We conclude that the removal of the gastric antrum in fetal sheep results in decreased plasma gastrin concentration, and that gastrin appears to have a regulatory or trophic role on the gut mucosa in these circumstances.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

PubMed1989

Effect of beta-adrenergic blockade on lung liquid secretion during fetal asphyxia.

The hypothesis tested in this study was that beta-adrenergic stimulation is responsible for the inhibition of fetal lung liquid production during moderate fetal asphyxia. In chronically catheterized fetal sheep, net lung liquid production rates were measured over three consecutive periods: a control period, a period of reduced uterine blood flow (RUBF) or epinephrine infusion, and periods of RUBF or epinephrine infusion in the presence of the beta-adrenergic receptor antagonist propranolol. The net production rate of fetal lung liquid was decreased from a mean control value of 7.7 +/- 1.0 to 1.5 +/- 0.4 ml/h (P less than 0.001) by RUBF; the administration of propranolol had no further effect on these liquid production rates (1.1 +/- 0.5 ml/h). In other experiments epinephrine infusion reduced the net production rate of fetal lung liquid from a mean control value of 7.2 +/- 1.4 to 1.7 +/- 1.8 ml/h (P less than 0.025); the addition of propranolol reversed this inhibition (secretion rate 6.1 +/- 1.4 ml/h, P less than 0.005). We conclude that the inhibition of fetal lung liquid production induced by moderate fetal asphyxia does not solely result from catecholamine stimulation of pulmonary beta-receptors.

Animals↗

PubMed1989

Bladder contractions and micturition in fetal sheep: their relation to behavioral states.

Fetal bladder contractions, indicative of micturition (voiding), and behavioral states were monitored in unanesthetized fetal sheep in utero during the last third of gestation. Fetal voids began during low-voltage electrocortical activity (LV ECoG) at a greater frequency (91.4 +/- 1.0%) than expected (57.2%) and began during high-voltage electrocortical activity (HV ECoG) with a lower frequency (8.7 +/- 1.0%) than expected (42.8%). Fetal voids began significantly sooner after the onset of LV ECoG (5.84 +/- 0.13 min) than after the onset of HV ECoG (10.88 +/- 0.04 min). Electroocular and nuchal muscle activities were associated with 96.2 and 66.0% of the voids, respectively, but there was no significant association between fetal voiding and swallowing episodes. Abolition of spontaneous voiding, by urine drainage (24 h), caused no significant differences, relative to a 24-h control period, in the duration or number of episodes of LV or HV ECoG or percentage of time spent in these states. Also, induction of voiding by infusing saline into the bladder did not significantly alter the time to the next change of ECoG state. However, the mean time to the next void and the mean volume of saline infused into the bladder to induce voiding tended to be less during LV ECoG than HV ECoG, although not significantly less. Our data show that most spontaneous voids in the fetus begin during LV ECoG, suggesting that voiding is regulated by descending information from the brain. Furthermore, these experiments demonstrate that fetal bladder contractions and voiding, either spontaneous or induced, do not influence the normal cycling of fetal ECoG states.

Animals↗

PubMed1989

Decline in lung liquid volume and secretion rate during oligohydramnios in fetal sheep.

Reduced amniotic fluid volume often results in fetal lung hypoplasia. Our aim was to examine the effects of prolonged drainage of amniotic and allantoic fluids on lung liquid volume (Vl), secretion rate (Vs), and tracheal flow rate (Vtr) in fetal sheep. In five experimental animals, amniotic and allantoic fluids were drained from 107 to 135 days of gestation. The volume of fluid drained from the experimental animals was 411.8 +/- 24.4 ml/day (n = 140). In six control animals, amniotic fluid volume was 747.7 +/- 89.7 ml (n = 15). Wet and dry lung weights were 20-25% lower in experimental fetuses than in control fetuses. Fetal hemoglobin, O2 saturation, arterial PO2, pH, and hematocrit were unchanged by drainage. During the drainage period, Vl was up to 65% lower, Vs was up to 35% lower, and Vtr was up to 40% lower in experimental fetuses than in control fetuses. We conclude that prolonged drainage of amniotic and allantoic fluids decreases Vl, Vs, and Vtr in fetal sheep. These findings indicate that fetal lung hypoplasia associated with oligohydramnios may be the result of a prolonged reduction in Vl.

Amniotic Fluid↗

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

The effects of intrauterine growth retardation on the development of the Purkinje cell dendritic tree in the cerebellar cortex of fetal sheep: a note on the ontogeny of the Purkinje cell.

The development of the fetal sheep cerebellum at 80, 100, 120 and 140 days gestation (term = 146 days) and 3 months postnatally was studied using Nissl stained sections and rapid Golgi preparations. The most rapid expansion of the Purkinje cell dendritic tree occurred between 100 and 120 days of gestation (5-6 fold increase in area). By 140 days it had acquired its adult form after which time growth continued mainly in the vertical direction. The effects of intrauterine growth retardation on the growth of granule and Purkinje cell dendrites in the cerebellar cortex of fetal sheep (140 days) were investigated in Golgi preparations. Compared with control cerebella the length (but not the number) of granule cell dendrites was reduced by 14% (P less than 0.01); the area of the Purkinje cell dendritic field was reduced by 20% (P less than 0.01); the branching density was reduced by 8% (P less than 0.01); the total branch length was reduced by 27% (P less than 0.002); the density of dendritic spines per row was not affected. These factors resulted in a decrease of 26% (P less than 0.002) in the total number of dendritic spines per row per Purkinje cell. These findings show that the growth of granule cell dendrites and the Purkinje cell dendritic tree have been significantly affected by chronic intrauterine deprivation. Such structural abnormalities could affect the pattern of neuronal connectivity and could be associated with functional deficits.

Animals↗

PubMed1988

Co-ordination of electrical activity in the myometrium of pregnant ewes.

The co-ordination of spontaneous and evoked electromyographic (EMG) activity was examined in the uterus of ewes from Day 100 of pregnancy and during labour. During pregnancy the onset of bursts of EMG activity was synchronous to within 2-3 min when recorded by electrodes at any recording site. Individual EMG spikes, whether occurring spontaneously or evoked by electrical stimulation of the myometrium, appeared to propagate between recording electrodes that were 1-3 cm apart, in the longitudinal or circular orientation of the uterus, but not when the electrodes were separated by more than 3 cm. Apparent conduction velocity in the longitudinal orientation was 7 cm sec-1 during pregnancy and increased to 13 cm sec-1 during labour. No consistent pattern could be distinguished in the sites at which EMG activity was first observed at any stage of pregnancy studied. The nature of propagation of EMG activity remains unresolved but it is clear that it is not initiated at a single site in the myometrium.

Animals↗

PubMed1988

Structure of the fetal sheep brain in experimental growth retardation.

A quantitative morphometric study of brain development has been made in growth-retarded fetal sheep. Intrauterine growth retardation was induced by removal of endometrial caruncles in the ewe prior to conception thereby reducing the size of the placenta in a subsequent pregnancy. Total brain and cerebellar weights were reduced by 21% (P less than 0.002) and the cerebrum by 20% (P less than 0.05) in the growth-retarded fetuses at 139 +/- 1 day (term = 146 days) compared with age matched control fetuses. Measurements of mean neuronal diameters were made on Purkinje cells, cerebellar granule cells, cortical cells in the motor and visual areas and hippocampal pyramidal cells; none were significantly different from control values. In growth-retarded fetuses compared with controls, there was a significant reduction in the thickness of the motor and visual cortices and the numerical density of neurones was significantly higher in these areas. In the cerebellar vermis, the number of Purkinje cells per unit surface area of Purkinje cell layer was higher, the numerical density of granule cells was significantly higher concomitant with a reduction in the area of the inner granular layer, and the area of the molecular layer was also reduced. In the hippocampal formation, the numerical density of pyramidal neurones was higher and the width of the stratum moleculare (dentate gyrus) was reduced. Migration of pyramidal neurones from the germinal layer to stratum pyramidale was not affected. These findings indicate that intrauterine growth retardation does not markedly affect cell size or neuronal migration (in the hippocampus) but does cause a significant reduction in the growth of the neuropil in the cerebellum, motor and visual cortices and the hippocampal formation.

Animals↗

PubMed1988

Lung liquid secretion, flow and volume in response to moderate asphyxia in fetal sheep.

The effects of moderate fetal asphyxia, induced by constriction of the maternal common internal iliac artery, on lung liquid secretion, tracheal fluid efflux and lung liquid volume have been investigated in unanaesthetized fetal sheep (111-142 days) in utero. During periods of fetal asphyxia the percent oxygen saturation, PO2, pH, and PCO2 of fetal carotid arterial blood changed from 57.2 +/- 1.3% (mean +/- SEM), 22.9 +/- 0.6 mmHg, 7.35 +/- 0.01 and 45.6 +/- 1.0 mmHg to 26.3 +/- 0.5% (P less than 0.001), 14.7 +/- 0.2 mmHg (P less than 0.001), 7.28 +/- 0.02, (P less than 0.001) and 47.8 +/- 0.4 mmHg (P less than 0.02), respectively. Fetal asphyxia, over 6 h, decreased the efflux of tracheal fluid from 7.07 +/- 0.47 ml/h to 3.97 +/- 0.36 ml/h (P less than 0.01) and, over 4 h, decreased the rate of lung liquid secretion from 9.42 +/- 1.76 ml/h to 4.91 +/- 1.54 ml/h (P less than 0.005), whereas it had no significant effect on lung liquid volume. The incidence of fetal breathing movements decreased from 52.9 +/- 2.5% to 22.6 +/- 3.5% during 6-h periods of fetal asphyxia. Thus, although fetal asphyxia decreased the net production of lung liquid, lung liquid volume was maintained probably, because the net efflux of fluid from the lungs via the trachea decreased to a similar extent.

Animals↗

PubMed1987

Respiratory and upper airway responses to nasal obstruction in awake lambs and ewes.

The aims of this study were to compare the ability of awake newborn lambs and adult sheep to breathe orally when the nasal route was blocked and to determine the means by which it was accomplished. Chronic EMG electrodes (diaphragm, genioglossus, geniohyoid, posterior crico-arytenoid, digastric, thyroarytenoid) and fibre-optic catheters were implanted in 10 lambs and 4 ewes. Before each study soft tubes were fixed into the nostrils allowing rapid blockade of the nasal ventilatory pathway. During nasal blockade inspiratory upper airway dilator EMG activity increased. SaO2 fell until mouth opening occurred, then returned to near control values; oral breathing then ceased leading to desaturation again. In lambs and ewes there was significant hypoxia, hypercapnia and acidaemia. In lambs 2-14 days old, PO2 and pH fell to lower levels than in older lambs (15-30 days) or ewes and PCO2 rose more. In lambs PCO2 gradually increased during the period of obstruction. We conclude that maintenance of blood gas homeostasis in newborn lambs is more severely impaired by nasal obstruction than in older lambs or ewes, possibly due to an immaturity of neural mechanisms controlling the creation of an oral airway.

Airway Obstruction↗

PubMed1987

Restoration of lung liquid volume following its acute alteration in fetal sheep.

1. The experiments were aimed at determining the means by which lung liquid volume is controlled in fetal sheep. Six unanaesthetized chronically catheterized fetuses between 121 and 144 days of gestation were used in experiments in which lung liquid volume was acutely reduced or increased. 2. The effects on lung liquid volume, secretion and flow in the trachea were continuously monitored until the original volume was restored. Tracheal pressure, breathing activity, electrocortical activity and laryngeal adductor muscle activity were also monitored. 3. Following a mean reduction in lung liquid volume of 54.1% (40.0 +/- 4.3 ml) there was a reduction in tracheal pressure of 1.91 +/- 0.26 mmHg. There was no change in the rate of lung liquid secretion and there was a near cessation in its rate of efflux from the trachea. Influx of liquid from the upper airway was rarely seen. 4. 5 h after its reduction, lung liquid volume had returned to control values. Tracheal pressure and the rate of liquid flow in the trachea returned to control values over 7-8 h. 5. In the hour following the reduction in lung liquid volume the incidence and amplitude of fetal inspiratory muscle electromyogram (e.m.g.) activity were reduced by 19% and 28% respectively. There was no change in laryngeal adductor muscle activity or in the duration of fetal sleep states. 6. When lung liquid volume was increased by 25.4 +/- 3.1 ml tracheal pressure increased by 2.01 +/- 0.17 mmHg. Although there was no change in the rate of liquid secretion there was a rapid efflux of liquid from the trachea principally during epochs of fetal breathing activity thus returning lung liquid volume to its control value. 7. Following the increase in lung liquid volume there were no changes in the incidence or amplitude of fetal inspiratory muscle activity, the activity of laryngeal adductor muscles or in the duration of sleep states. 8. It is concluded that following its alteration in fetal sheep lung liquid volume is restored by passive means. There was no evidence of volume-receptive neural reflexes being activated in defence of lung liquid volume.

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↗