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Biomedical subjects

R S Comline

Publications and source records attributed to R S Comline.

At least 19 recordsLinked to original sources
PubMed1989

The effects of insulin on the growth rate of the sheep fetus during late gestation.

The effects of insulin on fetal growth rates were investigated by measuring crown-rump length (CRL) chronically in sheep fetuses before and after pancreatectomy, sham operation or pancreatectomy accompanied by insulin-replacement treatment. Pancreatectomy of the fetus produced hypoinsulinaemia and reduced the daily and total increments in CRL by 40-50% over the last 20-30 days of gestation. The growth rate fell immediately after pancreatectomy and remained low throughout the rest of gestation. In contrast to the sham-operated fetus no pre-partum decline in the growth rate was observed in the pancreatectomized animal. The body weight, limb lengths and actual CRL at delivery were also significantly less after pancreatectomy than in the sham-operated animals. When fetal insulin levels were maintained after pancreatectomy by exogenous insulin infusion, the daily and total increments in CRL and the body size at delivery were restored to their normal values. Raising insulin levels above normal in the pancreatectomized fetus did not lead to additional fetal growth. When the data from all the fetuses were combined irrespective of treatment, there were significant positive correlations between the plasma insulin concentration in utero and the mean daily increment in CRL after treatment and between the former value and the body weight at delivery. These observations demonstrate that insulin is a major determinant of the growth rate in utero and that it is required throughout late gestation for the normal growth and development of the sheep fetus. They also indicate that insulin deficiency is probably the primary cause of the growth retardation observed after fetal pancreatectomy.

Animals↗
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↗
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

The effects of pancreatectomy on the sheep fetus in utero.

The effects of the removal of the fetal pancreas on the fetal metabolite concentrations and body weight have been investigated in chronically catheterized sheep fetuses during the last third of gestation. Between 390 and 1175 mg of pancreatic tissue was removed under halothane anaesthesia from sixteen fetuses between 113 and 121 d of gestation (term = 147 +/- 2d). In six fetuses from which 928 +/- 58 mg of pancreas had been removed the insulin level (3.4 +/- 0.3 micro micron/ml, n = 6) was below or equal to the limit of sensitivity of the assay. As only very small pieces of pancreas, if any, could be found in these fetuses at delivery, removal of the pancreas was regarded as complete in these animals. Pancreatectomy was incomplete in five fetuses from which 659 +/- 62 mg of pancreas had been removed. Insulin was detected in the plasma of these fetuses although the mean concentration (9.1 +/- 0.7 micro micron./ml, n = 5) significantly less than that in sham-operated animals (P less than 0.01). Small fragments of pancreas (0-26 mg) containing endocrine cells were found in these fetuses at delivery. Fetuses from which less than 50% of the pancreas had been removed had plasma insulin and metabolite concentrations similar to those of the sham-operated fetuses. Significant amounts of histologically normal pancreas were found in these fetuses at delivery. The plasma concentrations of glucose, fructose and alpha-amino nitrogen were significantly greater in the incompletely and completely pancreatectomized fetuses than in the sham-operated animals (P less than 0.01). In addition, the completely pancreatectomized animals also had higher plasma levels of lactate and free fatty acids than the sham-operated fetuses (P less than 0.01). There were no significant differences in the urea concentrations between sham-operated and pancreatectomized fetuses, but the fetal to maternal concentration difference in arterial plasma urea was greatest in the completely pancreatectomized fetuses (P less than 0.05). The hypoinsulinaemic fetuses were significantly smaller in birth weight than the sham-operated animals (P less than 0.02). The results show that removal of about 70% of the fetal pancreas will produce hypoinsulinaemia in the fetus and confirm that the pancreas is essential for normal growth and development in utero.

Animals↗
PubMed1983

Adrenal cortex of fetal lamb: changes after hypophysectomy and effects of Synacthen on cytoarchitecture and secretory activity.

The effects of hypophysectomy on the cell population of the adrenal cortex has been examined with light and electron microscopy. The sensitivity of the adrenal cortical cells to exogenous ACTH in both normal and hypophysectomized fetuses has been investigated by comparing plasma cortisol concentrations with structural changes in the adrenal cortex. Hypophysectomy was carried out at about 100 d and the subsequent analysis was made at about 135 d on fetuses catheterized at least 6 d earlier. The zona fasciculata of intact fetuses contained about 25% mature and 75% immature cells at 130-136 d. After hypophysectomy this zone contained a uniform population of immature cells and no mature cells; there was a significant reduction in both adrenal weight and cortical thickness. The zona glomerulosa was unaffected by hypophysectomy. The infusion of Synacthen 0 . 25 mg/d I.V. for 48 h did not affect the zona glomerulosa but resulted in a 2-fold increase in the thickness of the zona fasciculata in hypophysectomized and intact fetuses. This cortical growth was due to both hypertrophy and hyperplasia. All the cells in the zona fasciculata were mature following Synacthen treatment in both groups. The most striking difference between the secretory response of the adrenal cortex to Synacthen in the two groups was found within 3-6 h of the onset of infusion. Within this period there was a significant increment in the plasma cortisol concentration in the intact fetuses while no response was observed in the hypophysectomized animals. After 12 h infusion by contrast, a steadily rising response was observed in both groups. There was a significant correlation between the final plasma cortisol concentration and both the adrenal weight and cortical thickness after 48 h treatment. The increased sensitivity of the adrenal cortex to exogenous ACTH as term approaches in the sheep is considered to be dependent upon the increasing proportion of mature zona fasciculata cells within the adrenal cortex.

Adrenal Cortex↗
PubMed1983

Changes in the blood flow to the digestive organs of sheep induced by feeding.

The blood flow to the digestive organs of nine sheep was determined by the use of isotopically labelled microspheres before, during and at 2 h and 4 h after feeding. Within 3 min of the start of feeding, the blood flow to the salivary glands and to the smooth muscle of the rumen and reticulum increased three-fold. The blood flow to the epithelium of the rumen and reticulum also increased before any appreciable effect on ruminal fermentation could have occurred. This increase in flow was greater in absolute but smaller in relative terms than that to the muscle. At 2 h after feeding blood flow to the epithelium of the rumen and reticulum was two to four times greater than before food was taken, while the flow to the smooth muscle of these organs had fallen to the level found before feeding. In the more distal parts of the gastrointestinal tract, blood flow changes in response to feeding were less pronounced and, where they occurred at all, consisted of decreases at different times. Thus blood flow to the omasum decreased during feeding but recovered thereafter, while the flows to abomasum, duodenum and ileum were not changed during feeding but were significantly lower at 2 h and 4 h later. In the rest of the small intestine and in the large intestine there were no significant changes in flow during the period of observation, nor were there any changes in the blood flow to pancreas or spleen. However, the flow to the omental and mesenteric fat declined abruptly on feeding and reached its minimal value 2 h afterwards. These results are in marked contrast to those reported in other species in that the subepithelial capillary plexus of the reticulum and rumen was the only region contributing to the increased hepatic portal blood flow after feeding.

Animals↗
PubMed1983

Fetal and maternal endocrine changes during the induction of parturition with the PGF analogue, cloprostenol, in chronically catheterized sows and fetuses.

Parturition was induced in 8 catheterized sows 24-27 h after a single injection of the prostaglandin F (PGF) analogue, cloprostenol (200 micrograms, intramuscular), given at 105-106 days (4 sows) and 109-111 days (4 sows); term = 115 days. All catheterized fetuses were in good condition during the course of the induction and a normal percentage of live births occurred, although the subsequent viability of the piglets appeared to depend on the presence of an adequate suckling reflex. Maternal endocrine changes following cloprostenol included: (1) a rapid drop in plasma progesterone, which fell to below 5 ng/ml within 4 h, (2) a subsequent rise in 13, 14 dihydro-15-oxo prostaglandin F (PGFM) at about 6 h, with an increase in the venous-arterial difference across the uterus, (3) a large prepartum rise in PGFM from about 12 h, (4) a transient rise and fall in plasma cortisol immediately after the cloprostenol and a subsequent rise during labour, and (5) no detectable change in total unconjugated plasma oestrogen. During failed induction (2 sows) maternal progesterone levels remained above 5 ng/ml. In the fetuses, no changes in plasma progesterone were detectable following cloprostenol or during labour although there was a significant increase at birth. Fetal plasma cortisol concentrations had increased significantly 2 h after the cloprostenol, but a much greater cortisol surge began at 16-20 h reaching a maximum at birth. Fetal plasma oestrogen levels also increased just before delivery. These findings show that when farrowing is induced prematurely, the majority of the maternal endocrine changes are similar to those preceding spontaneous labour. However, the gradual rise in fetal plasma cortisol, which normally begins 4-6 days before term, is circumvented; instead a very rapid fetal cortisol surge begins after rather than before the drop in maternal progesterone and rise in PGFM. This results in high neonatal plasma cortisol levels in both catheterized and non-operated piglets and may well account for their viability.

Animals↗
PubMed1982

Pancreatic beta cell function in the fetal pig and sow.

Insulin secretion was investigated in acutely anaesthetized and chronically catheterized sows and their fetuses during late gestation. In the conscious animals, the mean fetal concentration of plasma insulin was 8.4 +/- 1.5 microunits/ml which was significantly less than the corresponding maternal value of 33.9 +/- 6.5 microunits/ml (n = 12, P less than 0.01). The plasma concentrations of insulin and glucose in the new-born piglets from these litters were not significantly different from the values observed in utero. The plasma concentration of insulin in the anaesthetized fetuses was significantly less than that in the chronically catheterized piglets over the same range of glucose levels. In the chronically catheterized animals, both fetal and maternal levels of insulin rose with increasing concentrations of plasma glucose while under acute conditions there was no correlation between the endogenous concentrations of insulin and glucose in either the fetuses or their mothers. Infusion of exogenous glucose (0.5 g as a 50% solution in 0.9% NaCl) stimulated the release of insulin in all the chronically catheterized fetuses studied but rarely increased the concentration of insulin in the anaesthetized fetusus. The present findings show that anaesthesia and surgery depress pancreatic beta cell function in the pig, particularly in the fetus.

Anesthesia, General↗
PubMed1981

Changes in plasma pancreatic polypeptide and gastrin in sows after eating and atropine.

Changes in plasma gastrin, pancreatic polypeptide and pulse rate were examined in three adult female pigs in which venous cannulae had been placed and in two of which arterial cannulae allowed sampling of arterial blood or recording of pulse rate. Gastrin, pancreatic polypeptide and pulse rate increased when the pigs ate after fasting overnight. Pancreatic polypeptide was reduced to or below resting levels following administration of atropine (25, 50 or 100 micrograms/kg intravenously) after which gastrin remained at about its previous levels or rose and pulse rates rose. It is concluded that in the pig, as in other species, there is a cholinergic muscarinic (atropine sensitive) mechanism contributing both to postprandial increases of pancreatic polypeptide and of gastrin.

Animals↗
PubMed1980

Pancreatic beta-cell function in the fetal foal and mare.

Insulin secretion and the factors influencing beta-cell function were investigated in the chronically catheterized fetal foal and mare during the second half of gestation. The response of the fetal beta cells to exogenous glucose was also examined. The mean concentration of insulin in the fetal foal was 7.5 +/- 0.5 (S.E.M.) microunit./ml (n = 20) which was significantly less than the corresponding maternal value of 49.0 +/- 5.0 microunit./ml (n = 20, P < 0.01). The insulin concentration in non-pregnant horses was 24.5 +/- 1.5 microunit./ml (n = 5) which was significantly less than the value in the pregnant animals (P < 0.01). However, there was no significant difference in the mean glucose concentration between the groups of adult animals. The insulin concentration was related to the endogenous glucose level in both adult and fetal horses. Wide variation in the maternal insulin concentration was observed above a glucose concentration of about 5.0 mmol/l. The mean concentration of insulin in pregnant mares decreased with increasing gestational age while the mean glucose concentration remained unaltered throughout the second half of gestation. There was no change in the basal concentrations of insulin or glucose in the fetus with gestational age although the fetal beta-cell response to exogenous glucose appeared to increase with increasing fetal age after 270 days of gestation (term 330 days). There was a significant arterio-venous difference in the concentration of insulin across the gravid uterus in the mare when the arterial insulin level was greater than 30 microunits./ml. Below this value, there was no consistent uptake of insulin by the uterus. The observations are discussed in relation to the regulation of insulin release in utero and the effects of pregnancy on maternal beta-cell function.

Animals↗
PubMed1979

Carbohydrate metabolism in the fetal pig during late gestation.

In acute experiments on pregnant sows under sodium pentobarbitone anaesthesia, acid base balance, oxygenation and plasma metabolite concentrations were well maintained in the dam and all fetuses which remained undisturbed in utero, irrespective of the duration of the experiment. Fetal liver glycogen concentrations were also unaffected by the time of removal of the fetus. By contrast, intravascular catheterization and withdrawal of blood led to fetal hyperglycaemia and depletion of hepatic glycogen although blood gas and pH values were not changed by these procedures. In the 1 1/2--2 h sampling period following catheterization the normal positive umbilical venous-arterial differences in plasma glucose and lactate generally became reversed. These changes were prevented by the administration of hexamethonium (10--15 mg . kg-1 i.v.) but the drug did not block the fall in hepatic glycogen in catheterized fetuses. Both adrenaline and noradrenaline, which were each infused intravenously at 2.7--3.9 or 0.6--0.9 microgram . kg-1 . min-1, resulted in fetal hyperglycaemia and lacticacidemia together with a fall in arterial blood pH; hepatic glycogen concentrations in these fetuses were also reduced. The apparent sensitivity of the glycogenolytic mechanism to surgical trauma and haemorrhage in the fetal piglet is discussed in relation to findings in other species.

Animals↗
PubMed1979

Prostaglandins in maternal and fetal plasma and in allantoic fluid during the second half of gestation in the mare.

The concentrations of the primary prostaglandins (PG) F-2alpha and E-2 and the metabolite 13,14-dihydro-15-oxo-prostaglandin (PGFM) in maternal and fetal plasma and in allantoic fluid were measured in chronically catheterized mares and fetuses. A gradual rise in all 3 PGs occurred with increasing gestational age. PGE-2 and PGF-2 alpha levels were highest in the allantoic fluid and lowest in the maternal plasma, whereas PGFM concentrations were greatest in maternal plasma. Significant venous-arterial plasma differences in PGFM concentration were detected across the uterine circulation between 180 and 280 days gestation. The 3--5-fold rise in maternal PGFM associated with fasting or intrauterine surgery was virtually abolished by meclofenamic acid, a prostaglandin synthetase inhibitor. Increases in PGE-2 and PGF-2 alpha in the fetal fluids preceded premature delivery of the foal, while PG changes in maternal plasma were minimal even 10--20 h before delivery.

Allantois↗