Daily changes in foetal and maternal blood of conscious pregnant ewes, with catheters in umbilical and uterine vessels

1. Blood gas tensions, pH, packed cell volume (PCV) and the levels of glucose, fructose and lactic acid have been followed in foetal and maternal blood for periods of 3-30 days in conscious ewes between 80 days gestation and term (∼ 147 days). 2. Blood samples were withdrawn through indwelling catheters placed in one or both umbilical vessels, a uterine vein and a maternal artery. 3. The success of the operation appeared to depend on the maintenance of maternal blood gas and pH levels within normal limits as well as on the final position of the tip of the catheter. The difficulties and limitations of the technique are discussed. 4. Foetal blood gas tensions, pH, PCV, lactic acid and glucose levels did not change markedly during the last 50-60 days of gestation. The fructose concentration fell during this period, the greatest change was between 100 and 120 days gestation. 5. Small fluctuations in P(O(2)), P(CO(2)) and pH in umbilical venous blood were associated with similar changes in the uterine vein, so that the gradients across the placenta appeared to remain constant. 6. Daily changes in maternal plasma glucose levels were reflected in similar changes in foetal plasma fructose and by much smaller alterations in the foetal glucose levels. The glucose concentration in the foetal plasma was less than 25% of that in maternal plasma. 7. The existence of a general relationship between maternal plasma glucose and foetal plasma fructose was masked by the independent fall in fructose levels with age. However, at any given stage of gestation, there was a significant correlation between foetal fructose and maternal glucose. 8. Few changes in the umbilical blood were associated with impending abortion or birth. Blood gas tensions remained constant, but a sharp fall in fructose levels often occurred 48 hr before any changes in pH, PCV and lactate concentration. 9. Present and other findings on conscious animals are compared with previous observations on acute, anaesthetized preparations

A comparative study of blood gas tensions, oxygen affinity and red cell 2,3 DPG concentrations in foetal and maternal blood in the mare, cow and sow

1. Blood gas tensions, pH, PCV, O(2) affinity and red cell 2,3-diphosphoglycerate (DPG) levels have been measured in uterine and umbilical blood in conscious cows and mares with indwelling vascular catheters and in sows under sodium pentobarbitone anaesthesia. 2. Large P(O(2)) gradients (20-24 mmHg) were observed between the uterine and umbilical venous blood in the cow and pig, while in the mare the corresponding P(O(2)) difference was only 2·7 ± 1·7 mmHg. Alterations in maternal arterial P(O(2)) did not affect the large vein-to-vein P(O(2)) difference in either ruminant or pig. 3. In the cow the presence of different haemoglobin types in the adult (A, AB or B) did not appear to affect the O(2) affinity. In six animals the mean P(50) of the foetal blood (24·8 mmHg) was considerably lower than that of the mother (35·5 mmHg); no changes in P(50) were observed during the last month of gestation. Red cell 2,3-DPG levels were higher in the calf foetus than in the mother, but in the ruminant 2,3-DPG has no effect on the affinity of haemoglobin for O(2) and the differences in P(50) between foetus and mother could be ascribed to the presence of a foetal haemoglobin. 4. In the sow large differences in O(2) affinity between foetal and maternal blood were observed, which were related to red cell 2,3-DPG concentration. A rise in foetal blood P(50) during the last half of gestation was associated with increased foetal weight and a rise in red cell 2,3-DPG. 5. In the mare the P(50) of the foetal blood was 2-5 mmHg below that of the mother. This difference appeared to be due to the lower 2,3-DPG concentration in the foetal red cells as in the sow; in both species the haemoglobin of the foetus is similar to that of the mother. 6. The differences in foetal and maternal O(2) affinity found in the various species and the changes which may occur during gestation or in the perinatal period are discussed in relation to the observed transplacental P(O)(2) gradients and the O(2) requirements of the foetus and neonate

P(O(2)), P(CO(2)) and pH levels in the umbilical and uterine blood of the mare and ewe

1. Foetal and maternal blood gas tensions and pH levels have been investigated in the mare and the ewe during late pregnancy under a number of experimental conditions. 2. Observations were made on anaesthetized animals with the foetus in utero. Simultaneous blood samples were withdrawn from a maternal artery and uterine vein, and from the two umbilical vessels, through catheters inserted at the beginning of each experiment. 3. At normal maternal arterial P(O(2)) (80-110 mm Hg) the umbilical venous P(O(2)) of the foal was very high (49 mm Hg) and the P(O(2)) in the umbilical artery (33 mm Hg) was similar to that in the umbilical vein of the lamb (34 mm Hg). 4. The P(O(2)) difference between the umbilical and uterine venous blood was 17 mm Hg in the ewe but only 4 mm Hg in the mare. The corresponding P(CO(2)) gradients were about one quarter of those for oxygen in both species. 5. When the maternal arterial P(O(2)) was raised above 100 mm Hg both uterine venous and umbilical P(O(2)) increased in the mare, and the gradient between the uterine vein and umbilical vein was reversed, whereas little change occurred in the corresponding vessels of the ewe. 6. Alterations in maternal arterial P(CO(2)) were associated with concomitant changes in the blood in the other three vessels but in both species the P(CO(2)) difference between uterine and umbilical venous blood appeared to remain constant. 7. Foetal blood pH levels followed those of the mother if the changes in the maternal blood were of respiratory origin. The effects of prolonged changes in maternal pH on foetal levels were investigated in the ewe. Foetal pH remained unchanged during maternal alkalaemia (pH 7·7) induced by Na(2)CO(3) infusions, but increased during a similar rise in maternal pH induced by hyperventilation. 8. The present observations have been compared with findings on the conscious animal and possible explanations for the differences between the two species are discussed

The development of the adrenal medulla of the foetal and new-born calf

1. The output of adrenaline and noradrenaline from the adrenal medulla during asphyxia, stimulation of the splanchnic nerves or the intra-arterial injection of acetylcholine, has been investigated in foetal and new-born calves up to 3 weeks of age. 2. Between 180 days' gestation and term (∼ 281 days) the response of the foetal adrenal gland of the calf to asphyxia appeared to be independent of its nerve supply and the discharge consisted largely of noradrenaline. A similar type of discharge was obtained after the intra-arterial injection of acetylcholine, but stimulation of the splanchnic nerves resulted in only a small discharge of both adrenaline and noradrenaline. 3. Rapid changes occurred in the response of the adrenal medulla to all forms of stimulation during the first 24 hr after birth. For the first 4-6 hr the adrenal medulla was hypersensitive; thereafter the response rapidly declined and a variable period of depressed excitability followed. The changes affected the output of noradrenaline rather than that of adrenaline and were more pronounced during asphyxia or after the intraarterial injection of acetylcholine. Within 24 hr of birth the amount of noradrenaline released in response to either form of stimulation was less than 25% of that found immediately after birth. 4. During the hypersensitive phase immediately after birth splanchnic nerve activity appeared to potentiate the direct effect of asphyxia on the noradrenaline cells since the maximum output of noradrenaline was attained more rapidly and at a higher P(O(2)) if the splanchnic nerves were intact. 5. The non-nervous direct response of the adrenal medulla to asphyxia decreased rapidly after birth and disappeared within 24 hr. It did not reappear at any age and was a feature of foetal life. 6. The recovery of the response to acetylcholine occurred between 3 and 8 days after birth with a return of the high level of noradrenaline secretion; no similar increase in the output of adrenaline occurred at this stage. 7. The response to asphyxia was not restored to the level found in the new-born calf until 2-3 weeks after birth. At this time the effect on the adrenal medulla appeared to be mediated almost entirely by the splanchnic nerves. 8. The effects of chloralose and pentobarbitone anaesthesia on the changes in the nervous response to asphyxia after birth were compared. Essentially the same pattern of changes was found with both anaesthetics although the absolute level of discharge under chloralose was greater and a considerably larger amount of adrenaline was secreted at 3 weeks of age. 9. At certain ages stimulation of the splanchnic nerves enhanced the response of the adrenal medulla to subsequent injections of acetylcholine. The noradrenaline output was only significantly increased by this procedure during the period of depressed excitability whereas the adrenaline discharge was always increased throughout the first 3 weeks of life. 10. The changes in adrenaline and noradrenaline content of the adrenal glands during the 3-week period after birth were investigated. The noradrenaline concentration was low immediately after birth during the hypersensitive phase and increased during the period of reduced sensitivity. The output of this amine was thus inversely related to its content in the adrenal gland. A similar relation did not occur with adrenaline, the concentration of which remained relatively constant during the first 3 weeks of life

Some aspects of foetal and uteroplacental metabolism in cows with indwelling umbilical and uterine vascular catheters.

1. The experiments were carried out on conscious pregnant Jersey cows with intravascular catheters implanted during late gestation in umbilical and uterine vessels. All but three of fifteen animals delivered live healthy calves. 2. Rountine daily analyses were made of blood gas tensions, pH and packed cell volume in foetal and maternal blood; plasma concentrations of glucose, fructose, lactate and urea were also determined. Measurements of plasma free fatty acids and blood acetate concentrations were made less frequently. Foetal heart rate and arterial blood pressure were recorded in animals with an umbilical arterial catheter. 3. The concentration differences between foetal and maternal blood or plasma in glucose, urea and acetate were measured in fifteen animals. The maternal-to-foetal glucose and acetate gradients across the placenta were high while the foetal-to-maternal plasma urea differences were small. 4. In those animals with patent arterial and venous catheters, uterine and umbilical blood flows were measured together with the arteriovenous differences in 02, glucose, acetate and lactate so that rates of foetal and uterine consumption could be estimated. The rates of utilization of O2, glucose and acetate by the foetus were lower than the values for the whole uterus, while the uteroplacental metabolism of these substrates was very high. 5. Significant amounts of lactate, which appeared to be produced by the uteroplacental tissue, were utilized by the foetus; the remainder passed into the uterine venous blood. 6. The total substrate/O2 quotient for the foetus, calculated from the utilization of known metabolites, appeared to be greater than 1. Thus, in the calf some carbon accumulation from sources other than amino acids, the uptake of which was not measured, would seem to occur. These results and the metabolic activity of the uterine tissues are discussed in relation to comparable findings in the sheep

Catecholamine secretion by the adrenal medulla of the foetal and new-born foal

1. The content and output of adrenaline and noradrenaline from the equine adrenal medulla has been investigated under different conditions in foetuses, foals and adult mares. 2. In the foetus only small amounts of both amines were secreted in response to stimulation of the peripheral ends of the splanchnic nerves to the gland; during anoxia the adrenal discharge was far greater and was independent of any nervous mechanism. 3. Whereas in the ruminant a direct adrenal response to low P(O(2)) is confined to the noradrenaline cells during foetal life only, the adrenal medulla of the foetal foal secreted both adrenaline and noradrenaline during asphyxia, and the direct response persisted for some days after birth. Noradrenaline was the amine predominantly released during asphyxia in the foetus. 4. Catecholamine output from the equine adrenal medulla changed with age, in that there was a gradual increase in both the absolute and relative amount of adrenaline released, irrespective of the stimulus applied, although at any given stage of development a higher proportion of adrenaline was secreted in response to stimulation of the splanchnic nerves than during anoxia. 5. The relative proportions of the two amines in the effluent blood bore little resemblance to those found in the glands, removed after prolonged asphyxia, in either foetuses or foals. Preliminary observations have indicated that more noradrenaline is present in the glands when the foetus remains relatively undisturbed within the uterus. 6. The possible significance of the larger adrenal response to asphyxia in the foetal foal in comparison with other species is discussed in relation to the development of the innervation and the growth of the adrenal cortex

The effects of bilateral adrenalectomy or hypophysectomy of the foetal lamb in utero.

1. Foetal hypophysectomy or bilateral adrenalectomy, carried out in utero at about 100 or 125 days gestation respectively, increased the length of gestation in sheep. It was confirmed that pregnancy was not prolonged significantly if hypophysectomy or adrenalectomy was carried out on one of a pair of twins. The hypophysectomized foetus was, however, smaller and the adrenalectomized foetus larger, than the unoperated twin. 2. In about half of the previously operated foetuses intravascular catheters were inserted into both mother and foetus, either at about 125 days, for a comparison with normal catheterized foetuses, or during the post-mature period. Both adrenalectomized and hypophysectomized foetuses appeared to have little resistance to stress or infection and the majority survived only 1-2 weeks after the insertion of catheters. 3. Maternal peripheral plasma oestrogen, progesterone and corticosteroid concentrations did not appear to be altered by either foetal hypophysectomy or adrenalectomy and were maintained in the normal range during prolonged gestation. 4. Foetal plasma oestrogen concentrations were significantly lower after hypophysectomy or adrenalectomy than values found in control lambs. Plasma progesterone values were low in all three groups of foetuses. 5. Plasma corticosteroid concentrations after foetal hypophysectomy (12-6 ng/ml.) or adrenalectomy (14-7 ng/ml.) were in the same range as the values for control lambs before the pre-partum rise (14-6 ng/ml.). However, there was a small but significant maternal-to-foetal plasma corticosteroid gradient in the two operated groups whereas this difference was not found in the control animals. 6. Tissue glycogen concentrations were measured in non-catheterized adrenalectomized and hypophysectomized foetuses. In these two groups, whether examined before 149 days or after prolonged gestation, liver glycogen concentrations were 30-40% of those in non-catheterized control foetuses at term. In other respects there was little apparent difference between adrenalectomized and control foetuses. 7. Hypophysectomized foetuses had significantly higher glycogen concentrations in heart, skeletal muscle and lung compared with control or adrenalectomized lambs. Plasma glucose and fructose values were also low in this group compared with control foetuses

The effects of insulin on the new-born calf

1. The normal variations in the concentrations of glucose, fructose and lactic acid in the blood of the calf which occur during the first few weeks after birth have been examined. 2. The responses of calves of different ages to intravenous injections of insulin have been examined by recording both the incidence of convulsions and the changes in the concentration of glucose, fructose and lactic acid in the blood. 3. New-born calves rarely convulsed during prolonged and severe hypoglycaemia and, if convulsions occurred, the onset was delayed by 6-8 hr. At 7 days of age convulsions usually followed the injection of insulin within 1½-2 hr. 4. No relationship could be found between the duration of hypoglycaemia and the incidence of convulsions at different ages. Hypoglycaemia was most prolonged in new-born calves which rarely convulsed. 5. Insulin hypoglycaemia during the first 24 hr after birth was associated with a rise in the concentration of lactate in the blood. Similar changes did not occur in calves at 7 days of age, in which the incidence of convulsions was much higher, or in weaned animals. 6. After both splanchnic nerves had been cut, insulin always caused convulsions in 24-hr-old calves. There was no rise in the blood lactate concentration in these animals. 7. Intravenous infusions of adrenaline but not noradrenaline in amounts similar to those known to be released from the adrenal medulla of the calf of this age prevented convulsions in 24-hr-old calves after section of the splanchnic nerves. These infusions had little effect on the blood glucose concentration but caused a similar rise in the lactic acid concentration to that found in normal animals at this age during hypoglycaemia. 8. At 7 days of age convulsions could only be prevented during hypoglycaemia by infusing larger doses of adrenaline which significantly raised the blood glucose concentration. The increase in the blood lactate concentration was less than that in the new-born animals. 9. The resistance to insulin hypoglycaemia which occurs immediately after birth is transient; it depends upon the release of adrenaline from the adrenal medulla and is associated with high concentrations of lactate in the blood during hypoglycaemia