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Biomedical subjects

G C Liggins

Publications and source records attributed to G C Liggins.

At least 91 records · Page 5Linked to original sources
PubMed1981

Prepartum maturation of the lung in fetal sheep: relation to cortisol.

We studied the relationship of certain fetal and maternal hormones to indicators of lung maturation in 12 fetal lambs delivered at gestational ages (GA) of 123-149 days. Maternal estrogen, maternal progesterone, and fetal prolactin did not correlate with GA or the indicators of fetal lung maturation. Fetal cortisol (range 4-165 ng X ml-1) increased with advancing GA (r = 0.747, P less than 0.01). All of the following showed a wide range of late gestation and showed a significant positive correlation with fetal cortisol: lung volumes at 40 cmH2O and 10 cmH2O on the deflation during air pressure-volume studies; saturated phosphatidylcholine (SPC) in lung tissue and in lavage fluid expressed both as mg X g-1 of wet lung and as percent of total phospholipids (%PL); total SPC (lung tissue plus lavage fluid): and SPC in lavage fluid as percent of total SPC. Lung DNA correlated inversely with GA and cortisol. All variables (except lavage fluid SPC as %PL) correlated more closely with cortisol than GA. Morphological development of lung was also related more closely to cortisol than GA. These results suggest that functional lung maturity is attained late in gestation and that endogenous cortisol is an important physiological factor in control of fetal lung maturation.

Animals↗
PubMed1981

Inhibitors of prostaglandin synthesis, tracheal fluid, and surfactant in fetal lambs.

To study their effects on tracheal fluid (TF) production and surfactant flux, we gave 12-h infusions of prostaglandin synthetase inhibitors (PGSI) on 16 occasions to 10 fetal lambs at gestational ages (GA) of 125--141 days. Results were similar with both sodium meclofenamate (13.9 +/- 3.4 mg.kg-1, 12 studies) and indomethacin (33.6 +/- 8.0 mg.kg-1, 4 studies). All studies were done at least 6 days after surgery and 4 days before spontaneous birth. During infusions of PGSI, there were no changes in fetal arterial blood pressure, pH, PaO2, PaCO2, TF production or its concentration of sodium, potassium, and chloride; calcium concentration in TF increased slightly. We expressed tracheal surfactant flux as micrograms.kg-1.h-1 of saturated phosphatidylcholine (SPC). If control SPC flux was less than 5 micrograms.kg-1.h-1 (10 studies at GA of 125--141 days), it did not change during infusion of PGSI; however, if control was greater than 5 micrograms.kg-1.h-1 (6 studies at GA 132--140 days), SPC flux decreased during the infusions in all studies. The results suggest that prostaglandins do not strongly influence TF production up to 4 days before birth and that prostaglandins are involved in the increased flux of surfactant which occurs in late gestation.

Animals↗
PubMed1981

Pulmonary maturation in the hypophysectomised ovine fetus. Differential responses to adrenocorticotrophin and cortisol.

Pulmonary maturation in six ovine fetuses hypophysectomised by a cryosurgical method at 0.7-0.8 of pregnancy and delivered by hysterotomy at 152.2 +/- 2.9 (SD) days was compared with that in seven control fetuses delivered at 144.5 +/- 3.5 days. Both the wet and the dry weight of the lungs was less in the hypophysectomised fetuses but total DNA did not differ. Lung volumes at 40 cm of H2O and at 5 cm of H2O on deflation in hypophysectomised fetuses were less than one-third that of controls. Saturated phosphatidylcholine, as an estimate of surfactant, was lower in both lung tissue and lavage fluid. A further group of hypophysectomised fetuses was infused intravenously either with cortisol at 1 mg/h for 72 h (n = 6), or with ACTH1-24 at 5 microgram/h for 84 h (n = 6) before delivery at 155.0 +/- 2.1 days and 154.2 +/- 3.9 days respectively. None of the indices of pulmonary maturation in the cortisol-treated fetuses differed from those in untreated hypophysectomised fetuses whereas values for lung volumes at 40 and 5 cm of H2O in ACTH-treated fetuses were more than twice those of untreated hypophysectomised fetuses and did not differ significantly from controls. In addition, the amount of saturated phosphatidylcholine in lavage fluid was greater in ACTH-treated fetuses (0.13 +/- 0.10 mg/g) than in untreated hypophysectomised fetuses (0.04 +/- 0.48 mg/g). Lung volume at 40 cm of H2O in four fetuses that were thyroidectomised at the time of hypophysectomy responded to ACTH as in hypophysectomised fetuses with intact thyroids but other indices were unaffected. We conclude that hypophysectomy retards pulmonary maturation in fetal sheep. Since ACTH restores distensibility and increases alveolar surfactant in the absence of other pituitary hormones it is likely that ACTH has a major role in lung maturation. The lack of response to cortisol suggests that the effect of ACTH is not mediated only by circulating cortisol.

Adrenocorticotropic Hormone↗
PubMed1981

Effects of partial lower aortic obstruction in the pregnant ewe on fetal arterial pressure, heart rate, plasma renin activity and prostaglandin E concentration.

Fetal haemodynamic changes, together with changes in the fetal renin-angiotensin system and in circulating concentration of prostaglandin E, were studied in chronically prepared fetal sheep before, during and after asphyxia induced acutely by maternal aortic occlusion in last third of gestation. A total of thirty experiments were performed in seventeen animals. Severe fetal asphyxia (fall in PO2 greater than 30%) was associated with transient fall in heart rate and rise in blood pressure but not with changes in plasma concentrations of either prostaglandin E or renin substrate. Fetal plasma renin activity increased to 140% of control values during moderate asphyxia and to 400% during severe asphyxia. We conclude that the fetal renal angiotensin-renin system is activated by asphyxia.

Animals↗
PubMed1981

Collagen content of human amniotic membranes: effect of gestation length and premature rupture.

The collagen content of amniotic membranes was measured in samples obtained at delivery from patients with and without premature rupture of the membranes (PROM). In samples from patients with PROM the collagen content (343 microgram/mg) was significantly lower than in samples from patients without PROM (373 microgram/mg) (P less than .005). The collagen content decreased between 32 and 40 weeks' gestation from 446 to 362 microgram/mg (r = .588; P less than .001) in patients without PROM and from 393 to 332 microgram/mg (r = -.362; P less than .05) in patients with PROM. The latent period between membrane rupture and delivery was not associated with a decrease in collagen content. The changes in amnion collagen during gestation and the differences observed with PROM suggest that weakening of the amnion in preparation for rupture may be determined partly by factors controlling the synthesis and degradation of collagen.

Amnion↗
PubMed1981

Glycosaminoglycans and collagen in human amnion from pregnancies with and without premature rupture of the membranes.

Glycosaminoglycans and collagen were measured in dried samples of human amnion from pregnancies with and without premature rupture of the membranes. The major sulphated glycosaminoglycans were dermatan and chondroitin sulphates. The concentration of sulphated glycosaminoglycans decreased significantly towards term in both groups of patients (with, r=--0.720, and without, r=-0.631, premature rupture of membranes), the decrease occurring earlier in gestation in the PROM group (P less than 0.005). There was a positive correlation between the sulphated glycosaminoglycan and collagen concentrations in both groups of samples (with, r = 0.697 and without, r = 0.493, premature rupture of membranes). The only unsulphated glycosaminoglycan identified in amnion was hyaluronate which was present in higher concentrations (P less than 0.005) in term samples (10.67 +/- 5.5 microgram/mg) than in pre-term samples (5.45 +/- 2.98 microgram/mg). There was a negative correlation between the hyaluronate and collagen concentrations (r = -0.455). The associations between decreasing concentration of both sulphated glycosaminoglycan and collagen with increasing concentrations of hyaluronate in amnion are consistent with observed changes in the tensile properties of the amnion towards term and are explicable in terms of accepted mechanisms of connective tissue remodelling.

Amnion↗
PubMed1981

The effect of spinal cord transection on lung development in fetal sheep.

The relationship of breathing movements to lung development in the ovine fetus was investigated by transecting the fetal cervical spinal cord above (C2-C3; n = 4) or below (C7-C8; n = 4) the phrenic nucleus at 114 days of gestation. The fetuses were delivered by hysterotomy at term and compared with a group of intact term fetuses (n = 8). Cord transection at C2-C3 resulted in a significant (P less than 0.05) reduction in wet weight of the lungs to 1.56 +/- 0.23% of body weight from 2.59 +/- 0.83% in the C7-C8 group. The diaphragms of the two groups did not differ in weight or histological appearance. Distensibility of the left lung with air at 40 cmH20 was significantly less in the C2-C3 group (6.8 +/- 3.5 ml.kg-1 body weight) than the C7-C8 group (19.9 +/- 3.7 ml.kg-1) or the intact controls (15.2 +/- 5.4 ml.kg-1). DNA content in the C2-C3 group (0.63 +/- 0.12 g) was less than in controls (0.99 +/- 0.19 g) but it was not different from the C7-C8 group (0.82 +/- 0.33 g.) DNA concentration, water content and saturated phosphatidylcholine concentration in lung tissue and lavage fluid were similar in the three groups. It is concluded that the absence of breathing movements caused by transection of the spinal cord above the phrenic nucleus is associated with retarded lung growth and maturation.

Animals↗
PubMed1981

The effect of bilateral thoracoplasty on lung development in fetal sheep.

The relationship of breathing movements to lung development in the ovine fetus was investigated by partially removing ribs on each side of the chest and closing the deficiencies with silicone membranes at 114 days of gestation; the increase in compliance of the chest wall that resulted caused blunting of the amplitude of phasic negative pressures recorded in the trachea to less than 10 torr. Compared to sham operated controls (n = 5), the lungs of the thoracoplasty group (n = 5) at term weighed significantly (P less than 0.05) less, both wet (1.5 +/- 0.2 v. 2.3 +/- 0.1% of body weight) and dry (0.14 +/- 0.01 v. 0.18 +/- 0.01% of body weight. In addition, DNA content of the thoracoplasty group was less than that of the control group (0.47 +/- 0.05 mg v. 0.72 +/- 0.20 mg). Distensibility of the left lung with air at 40 cmH20 was less than in the thoracoplasty group than in controls (10.0 +/- 2.0 v. 18.9 +/- 3.0 ml.kg-1 body weight) but no differences were found in the concentrations of saturated phosphatidylcholine in lung tissue and lavage fluid, in DNA concentrations or in the amount of lung water (as % of wet weight of lung). It is concluded that phasic negative pressures of normal intensity are necessary for normal development of the fetal lungs.

Animals↗
PubMed1980

Production rates of prostaglandin F, 6-keto-PGF1 alpha and thromboxane B2 by perifused human endometrium.

Human endometrium obtained from fresh hysterectomy specimens was perifused for 7 hr in 95% O2/5% CO2 at 37 degrees C. The phase of the menstrual cycle was determined by histological examination. The concentrations of PGF, 6-keto-PGF1 alpha and TxB2 in 20 min fractions of the perifusion medium were measured by radioimmunoassay and production rates were calculated in terms of dry weight of tissue. Biphasic patterns of production were observed; high initial values fell to about 20% at 2 hr and then increased to relatively stable values at about 4 hr which were maintained for the next 2 hr. During this latter period, production rates in endometria taken at different phases of the cycle differed markedly from each other; the production rates of PGF in secretory and early proliferative endometria were low (15.8 +/- 2.6, mean +/- SEM and 67.2 +/- 8.3 ng/min/g respectively) whereas they were high in late proliferative and premenstrual endometria (188.0 +/- 16.7 and 196.4 +/- 16.9 ng/min/g respectively). The patterns of production of 6-keto-PGF1 alpha and TxB2 were similar to those of PGF but the absolute values were much lower (less than 10%). We conclude that the observed rates of production of prostaglandins by perifused human endometrium are consistent with synthesis being stimulated either by estrogen or withdrawal of hormonal support and being inhibited by progesterone.

6-Ketoprostaglandin F1 alpha↗
PubMed1980

Effects of frusemide on plasma concentrations of renin and prostaglandins E and A in fetal sheep.

The role of the renin-angiotensin system and prostaglandins in the regulation of fetal vascular homeostasis was investigated by measuring hemodynamic and hormonal responses to fetal administration of frusemide in ten intact and five bilaterally nephrectomised fetal lambs. The increase in fetal arterial pH and the fall in pCO2 following treatment with frusemide suggests that this drug may influence placental exchange of blood gases. The increase in plasma renin activity without accompanying changes in plasma PGE does not support a direct relationship between renin release and renal prostaglandin E production in the fetal lamb.

Angiotensin I↗
PubMed1980

Differential production of PGF and 6-keto-PGF1 alpha by the rat endometrium and myometrium in response to oxytocin, catecholamines and calcium ionophore.

Uterine horns for castrated, estrogen-treated rats wee superfused for 6 hours in 95% O2/5% CO2 at 37 degrees C. The method of superfusion in which medium flows separately over the inner and outer surfaces of the horn allows prostaglandin synthesis in the myometrium and endometrium to be measured independently while their anatomical relationship is undisturbed. Prostaglandins were measured by radioimmunoassay. They myometrium formed more 6-keto-PGF1 alpha than PGF whereas the opposite was true of the endometrium. Production rates of TxB2 in both tissues were relatively low. The addition of inophore A-23187, oxytocin or phenylephrine to the superfusion medium not only increased the myometrial production rates of both 6-keto-PGF1 alpha and PGF but also increased the ratio of 6-keto-PGF1 alpha:PGF. Neither ionophore nor phenylephrine affected the rate of prostaglandin synthesis in the endometrium whereas oxytocin caused a significant increase in the production rate of PGF. We conclude that the large amounts of 6-keto-PGF1 alpha in the myometrial superfusate probably originate in both the smooth-muscle cells of the myometrium and the endothelium of the myometrial blood vessels. The differential responses to ionophore A-23187, phenylephrine and oxytocin suggest differences in the mode of their regulation of prostaglandin synthesis.

6-Ketoprostaglandin F1 alpha↗
PubMed1980

Fetal cardiovascular and metabolic responses to simulated diving in the Weddell seal.

Fetal responses to normobaric diving simulated by submersion of the maternal head for 20 min were studied in four conscious Weddell seals near term. Microspheres injected into the maternal aorta were distributed to the placenta and kidneys in the ratio of 0.4 in the control period and 19.3 during diving, suggesting minimal placental vasoconstriction. Fetal heart rate fell during diving from a mean control value of 90 to 34 beats/min after 4 min. The onset of fetal bradycardia was not consistently associated with changes in blood gas tensions. Diving was associated with a fall in fetal arterial O2 tension from 24 to 9 Torr, arterial CO2 tension rose from 47 to 85 Torr, and arterial pH fell from 7.35 to 7.24. Fetal-maternal gradients for CO2 and H+ transport remained constant, whereas the gradient for O2 transport fell from 47 Torr before diving to 14 Torr at the end of diving. Blood lactate concentrations increased three- to fourfold during diving and reached peak values 10-15 min after diving ended. The similarity of the fetal and maternal heart rate responses to diving is consistent with the presence of physiological oxygen-conserving reflexes akin to the adult's.

Animals↗
PubMed1980

Steroid and growth hormone levels in premature infants after prenatal betamethasone therapy to prevent respiratory distress syndrome.

Prenatal maternal therapy with glucocorticoid reduces the incidence of respiratory distress syndrome (RDS) in premature infants. To investigate the effects of this treatment on the fetal endocrine system, we determined serum concentrations of betamethasone, cortisol, dehydroepiandrosterone sulfate, growth hormone, and prolactin in cord blood of 215 treated infants and 117 untreated infants of 26--36 wk of gestation. Cortisol levels are suppressed within 6 hr of betamethasone treatment, decrease to 45% of the concentration in untreated infants (8.4 micrograms/dl), and return to normal by 7 days. Dehydroepiandrosterone sulfate is reduced maximally by 65% and returns to normal concentrations (123.5 micrograms/dl in 7 1/2 days. The suppression of both steroids was similar after treatment with 12 mg betamethasone (acetate and phosphate) daily 2 times or with 6 mg betamethasone (alcohol) twice daily 4 times. Peak betamethasone levels were higher after the 12 mg dose, but the two-treatment regimens produced a similar total exposure of the fetus to elevated serum glucocorticoid activity for 2 1/2 days and decreased plasma activity for the subsequent 4 1/2 days. Treated infants with low cortisol concentrations at birth increased their cortisol levels severalfold after birth in response to either intrapartum asphyxia or RDS. Betamethasone therapy did not affect cord serum prolactin levels, but the concentration of growth hormone was reduced at all ages. The suppression was greatest (53% decrease) among infants of 28 less than 32 wk, and, among older infants, there was a subsequent increase above control levels between 2 and 4 days after treatment. This study indicates that prenatal betamethasone treatment causes a transient suppression of fetal growth hormone and presumably those pituitary hormones which regulate steroid production by both the definitive and fetal zones of the fetal adrenal. However, the suppression of fetal cortisol does not interfere with the pituitary-adrenocortical response to stress after birth.

Betamethasone↗
PubMed1980

Adrenocortical responses to adrenocorticotrophin in the hypophysectomized ovine fetus.

Fetal adrenocortical responsiveness to ACTH declines during 90-120 days gestation and fetal pituitary peptides have been implicated in this refractoriness. In these studies the ACTH-induced cortisol responses were measured in 11 ovine fetuses of 114 days gestation. Five animals were hypophysectomized as evidenced by prolonged gestation, pituitary histology, TRH-testing, delayed maturation and decreasing fetal plasma prolactin concentrations (less than 1 ng.ml-1) (P less than 0.005). Resting cortisol concentrations decreased from 22.4 to 8.1 ng.ml-1 in the hypophysectomy group and were not different from the control group (19.6-14.9 ng.ml-1) over the 5 days of study. Responses measured as increments in plasma cortisol concentrations increased equally and successively in both groups. Since pituitary ablation fails to enhance fetal adrenal responsiveness to ACTH we conclude that refractoriness is unlikely to be caused by an inhibitor of pituitary origin.

Adrenal Cortex↗
PubMed1980

Growth and cytodifferentiation of the fetal lamb adrenal cortex prior to parturition.

Growth patterns and cytodifferentiation of the fetal lamb adrenal cortex, from 136 days of gestation to birth at normal term, have been examined. The gland almost doubles in weight over this period (0.45--0.80 g) and the inner cortical zone (zona fasciculata+zona reticularis) nearly quadruples in thickness (0.33--1.25 mm). The phase of rapid growth has begun by 136 days, and the growth patterns are essentially linear. The inner cortical zone consists of light and dark cells, the former increasing in number proportionately more than the dark cells. This change in the cell ratio is linked with increased fetal production of cortisol. As growth and differentiation proceed the light cells increasingly possess a more vesicular SER; mitochondria of the orthodox configuration, with predominantly vesicular cristae; a well developed Golgi complex with numerous small, bristle coated vesicles; and dark granules near the Golgi complex, in the peripheral cytoplasm, and external to the cells. The sixfold increase in the volume of the inner cortical zone and the ultrastructural evidence of cytodifferentiation appear adequate to account for the known increase in the fetal synthesis of cortisol during this stage of pregnancy.

Adrenal Cortex↗