Biomedical subjects

S B Hooper

Publications and source records attributed to S B Hooper.

At least 19 recordsLinked to original sources

PubMed1998

Effects of prostaglandin E2 on renal function and lung liquid dynamics in foetal sheep.

1. The aim of the present study was to determine the effects of prolonged prostaglandin E2 (PGE2) administration on the function of the foetal kidneys and lungs in order to gain a greater understanding of the role played by PGE2 in the control of foetal fluid balance. By studying the effects of PGE2 at two gestational ages, we have also been able to examine the influence of age. 2. We studied the effects of 26 h PGE2 infusion on foetal sheep at a mean (+/- SEM) of 120.0 +/- 0.6 (n = 6) and 139.0 +/- 0.8 (n = 4) days of gestation. In both groups, foetal urine production was significantly inhibited throughout the infusion period (P < 0.05). In younger, but not older foetuses, urine production returned to control values within 24 h of ending the infusion (P < 0.05). This PGE2-induced anti-diuresis was associated with foetal hypoxaemia and acidaemia, a reduction in free water clearance and an increase in foetal plasma arginine vasopressin concentrations (P < 0.05). 3. During PGE2 infusions, foetal breathing movements were inhibited, the effect being greater and more sustained in older foetuses (P < 0.05). 4. Infusions of PGE2 led to increased lung liquid production at both ages (P < 0.05); lung liquid volumes were reduced in older foetuses (P < 0.05), but were unchanged in younger foetuses. The reduction in lung liquid volume in older foetuses may have been due to inhibition of foetal breathing. 5. We conclude that increased circulating levels of PGE2 have profound effects on foetal renal and lung function which, if sustained, could compromise foetal lung development and perinatal well-being.

Animals↗

PubMed1998

Role of luminal volume changes in the increase in pulmonary blood flow at birth in sheep.

The mechanism by which pulmonary blood flow increases and pulmonary vascular resistance decreases after birth is not fully understood. The aim of this study was to simulate the decrease in lung volume caused by the onset of air-breathing at birth and determine whether it can duplicate the changes in pulmonary blood flow and vascular resistance that occur at this time. In chronically catheterized fetal sheep near term (145 days of gestation), fetal pulmonary arterial blood flow was measured, using coloured microspheres, before and after fetal lung liquid volumes were reduced from 52.2 +/- 2.7 to 21.2 +/- 1.6 ml kg-1. During the 30 min period following the reduction in lung liquid volume, the pulmonary-to-systemic arterial pressure difference decreased from 6.8 +/- 1.2 mmHg (pulmonary > systemic) to 1.6 +/- 0.5 mmHg. Reducing the volume of fetal lung liquid increased pulmonary blood flow from 59.1 +/- 10.5 to 204.2 +/- 40.4 ml min-1 (100 g tissue)-1 and reduced pulmonary vascular resistance from 0.53 +/- 0.20 to 0.14 +/- 0.04 mmHg min ml-1 (100 g tissue)-1. We conclude that a reduction in fetal lung liquid volume, which simulates the reduction in lung volume that occurs at birth, causes a 3- to 4-fold increase in pulmonary blood flow and a reduction in pulmonary vascular resistance of a similar magnitude. Thus, the reduction in lung volume associated with the lung changing from a liquid- to an air-filled organ, may partly account for the increase in pulmonary blood flow and decrease in pulmonary vascular resistance at birth.

Animals↗

PubMed1998

Stimulation of lung growth by tracheal obstruction in fetal sheep: relation to luminal pressure and lung liquid volume.

Obstruction of the fetal trachea causes liquid to accumulate within the future airways, which is a potent stimulus for lung growth. Our aim was to determine the relationship between the increase in fetal lung growth after tracheal obstruction and the increases in lung liquid volume and tracheal pressure to better understand the mechanisms involved in the growth response. The effects of 4 and 10 d of tracheal obstruction on lung DNA and protein contents and DNA synthesis rates were determined; these data were combined with data collected previously after 2 and 7 d of tracheal obstruction. Fetal lung liquid volumes and secretion rates were measured before (d 0) and on d 1, 2, 4, 7, and 10 after tracheal obstruction; fetal tracheal pressures were monitored throughout this period. Tracheal pressures increased from 2.9 +/- 0.8 mm Hg (control) to 4.3 +/- 0.4 mm Hg within 1 d of tracheal obstruction and remained at this elevated level for the duration of the obstruction period. Lung liquid volume increased progressively from 24.7 +/- 1.1 mL/kg on d 0 to 97.3 +/- 15.2 mL/kg at d 7 of tracheal obstruction, but had not increased further by d 10. Tracheal obstruction significantly increased lung DNA and protein contents above control values; over the 10-d period the increase in lung DNA content was closely related (r = 0.99) to the increase in lung liquid volume, but not to the increase in tracheal pressure. DNA synthesis rates were increased at 4 d of tracheal obstruction (by 66%) but had returned to control levels by d 10. We conclude that: 1) the mechanisms responsible for the acceleration in lung growth induced by tracheal obstruction are most active on d 2, remain active at a reduced level on d 4 and 7, and have returned to control levels by d 10; and 2) the increase in lung DNA content during tracheal obstruction (d 2-7) is closely related to the increase in lung liquid volume, but not to the increase in intraluminal pressure. Thus, we suggest that an increase in lung expansion is one of the primary factors responsible for the acceleration in fetal lung growth induced by tracheal obstruction.

Airway Obstruction↗

PubMed1997

The vulnerability of the fetal sheep brain to hypoxemia at mid-gestation.

Our aim was to test the hypothesis that a brief episode of hypoxemia near mid-gestation in fetal sheep will result in damage to the fetal brain with the extent and type of damage in any particular region being related to the developmental processes occurring at the time of the insult. Hypoxemia was induced, sufficient to reduce arterial O2 content by approximately 50%, by restricting utero-placental blood flow in 14 chronically catheterised fetuses for 6 h or 12 h at 84 days of gestation (term 145-8 days). Age-matched fetuses (n = 14; 4 operated and 10 unoperated) were used as controls. Fetuses were killed 7 days after being exposed to hypoxemia, and brains removed for histological analysis at the light and ultrastructural levels. Body weights of hypoxemic fetuses did not differ significantly from controls but brain weights were significantly reduced both in absolute terms and when expressed in relation to body weight (P < 0.05). Most fetuses exposed to hypoxemia sustained no gross brain damage. However, in one hypoxemic fetus from a multiple pregnancy there was extensive leucomalacia in the cortical white matter; mild focal damage was seen in another 8 hypoxemic fetuses. In the cerebral cortex (frontal lobe) the surface folding index was significantly reduced (P < 0.05) in hypoxemic fetuses compared to controls suggesting that gyral formation had been delayed. In these fetuses there were also degenerating neurons in the deeper cortical layers. In the hippocampus of hypoxemic fetuses there was a delay (P < 0.05), compared to controls, in the migration of cells from the germinal layer to the pyramidal layer in the CA1 region, and decreases (P < 0.05) in the density (area1) of neurons in the pyramidal layer and in the width of stratum oriens. In the cerebellum of hypoxemic fetuses there was a decrease (P < 0.05), compared to controls, in the density (area1) of mitotic bodies in the external granule cell layer. However, there were no significant differences in the number of pyknotic cells in this layer, in the density of Purkinje cells, in their somal area, or in the width of the external granule cell or molecular layers. There was an increase (P < 0.05) in the proportion of the brain parenchyma occupied by blood vessels in both the hippocampus and cortex of hypoxemic fetuses compared to controls. This study has shown that an hypoxemic insult near mid-gestation can result, one week later, in white matter damage and in neuronal death in the hippocampus and to a lesser extent in the cerebral cortex and cerebellum. It can also retard neuronal migration and the growth of neural processes in the hippocampus where development is well established at this age. Such brain damage could result in less than optimal neuronal connectivity and could affect function postnatally.

Animals↗

PubMed1997

Cortisol pretreatment enhances the lung growth response to tracheal obstruction in fetal sheep.

We have investigated whether cortisol pretreatment of sheep fetuses will result in a greater liquid accumulation within the lung and a greater lung growth response to obstruction of the fetal trachea. Chronically catheterized fetal sheep received either 1) a cortisol infusion at an increasing dose (1.5-4.0 mg/day) from days 118 to 127 of gestation; the fetal trachea was then obstructed from days 128 to 131 of gestation (n = 4); 2) a saline infusion from days 118 to 127 of gestation; the fetal trachea was then obstructed from days 128 to 131 of gestation (n = 4); or 3) a saline infusion from days 118 to 127 of gestation with no period of tracheal obstruction (control; n = 4). Fetal tracheal pressures were measured from days 128 to 131 of gestation, whereas lung liquid secretion rates and volumes were measured on days 118, 128, and 131 of gestation. On day 131 of gestation, all fetuses were given an intravenous injection of [3H]thymidine and were killed 8 h later. Cortisol pretreatment increased the volume of liquid that accumulated within the fetal lung from 69.5 +/- 4.1 to 96.1 +/- 14.1 ml/kg after 3 days of tracheal obstruction. Similarly, cortisol pretreatment significantly enhanced the increase in lung DNA content from 257.4 +/- 11.0 to 309.1 +/- 16.3 mg/kg after 3 days of tracheal obstruction. We conclude that pretreatment of fetuses with cortisol increases the volume of liquid that accumulates after tracheal obstruction and, as a result, increases the fetal lung growth response to tracheal obstruction.

Animals↗

PubMed1997

Effect of hypoxemia on tissue glycogen content and glycolytic enzyme activities in fetal sheep.

We have tested the hypothesis that prolonged fetal hypoxemia causes a reduction in glycogenolytic enzyme activities and/or a depletion of fetal glycogen stores. We compared the effects of short (4 h) and prolonged (24 h) periods of reduced maternal uterine blood flow (RUBF) on glycogen content and on the activities of glucose-6-phosphatase (G-6-Pase), glycogen phosphorylase (GPase), and glycogen synthase (GSase) in selected fetal tissues. RUBF was reduced in 10 pregnant sheep at 135 days of gestation (term approximately 146 days) for either 4 h (n = 5) or 24 h (n = 5); 5 other fetuses were used as controls. During RUBF, fetal SaC2 was decreased from 61.6 +/- 3.9 to 22.0 +/- 1.4% at 4 h and to 26.7 +/- 1.2% at 24 h. Hepatic glycogen content was significantly reduced at 4 h of RUBF, but was not reduced further at 24 h. Fetal liver GPase (active and total enzyme activity) and G-6-Pase activities were reduced at 4 h of RUBF but tended to return toward control values at 24 h. Similarly, hepatic GSase activity tended to decrease at 4 h of RUBF, although the reduction was not quite significant (P = 0.08). We conclude that RUBF causes a reduction of fetal glycogen stores and a reduction in G-6-Pase and GPase activity at 4 h. Fetal tissue glycogen contents were not reduced further at 24 h, compared with 4 h of RUBF, which indicates that fetal glycogenolysis is reduced during this time, probably because of the inhibition of GPase and G-6-Pase. It is not known why the activities of these enzymes are reduced during prolonged RUBF, when circulating epinephrine and norepinephrine concentrations are high.

Animals↗

PubMed1997

Lung liquid production rates and volumes do not decrease before labor in healthy fetal sheep.

Previous studies have suggested that the volume and production rate of fetal lung liquid decrease late in gestation, before the onset of labor, in preparation for the clearance of lung liquid at birth. In contrast, our earlier studies have not shown a decrease in lung liquid volume near term, although these studies were not continued to the onset of labor. Our aim was to determine the changes in lung liquid volume and production rate in fetal sheep during the last 2 wk of gestation up to the onset of labor at term (approximately 147 days). In eight chronically catheterized fetal sheep, the volume and production rate of fetal lung liquid were measured at 130, 135, and 140 days of gestation and then on every 2nd day until the onset of labor. Labor was detected by monitoring uterine muscle activity and intrauterine pressure changes. On the day of labor onset, which occurred at 147 +/- 1 days of gestation, fetuses weighted 5.0 +/- 0.2 kg. The volume of fetal lung liquid was 40.4 +/- 2.7 ml/kg at 19 +/- 1 days before labor onset and had not significantly changed by 0.7 +/- 0.2 days (44.8 +/- 5.1 ml/kg) before labor. Similarly, lung liquid production rates at 19 +/- 1 days before labor (5.1 +/- 1.8 ml.h-1.kg-1) were not significantly different from those at 0.7 +/- 0.2 days before labor (3.4 +/- 0.7 ml.h-1.kg-1). We conclude that, in healthy ovine fetuses, lung liquid volumes and production rates do not decrease before the onset of labor. Our results indicate that the entire volume of fetal lung liquid (approximately 222.5 +/- 36.6 ml) must be cleared after the onset of labor.

Animals↗

PubMed1996

Acidaemia enhances the inhibitory effect of hypoxia on fetal lung liquid secretion in sheep.

Previous studies have shown that moderate fetal asphyxia reduces the secretion rate of fetal lung liquid. The present aim was to determine the relative effects of the individual components of asphyxia (hypoxia, hypercapnia and acidaemia) on lung liquid secretion in fetal sheep. Fetal hyperoxia was also studied to determine the extent to which lung liquid secretion is restricted by the relatively low fetal blood PO2. As each manipulation of fetal blood gas tensions and pH treatment produced alterations in more than one aspect of blood composition, data from all treatment groups were combined and a multiple analysis of variance was performed to determine the separate effects of PaO2, PaCO2, SaO2 and pHa. Lung liquid secretion rate was significantly reduced when mean PaO2 values were below 24.5 mmHg (range 12.9-24.3 mmHg). When PaO2 values below 24.5 mmHg occurred in combination with pHa values below 7.275 (range 6.934-7.268) the secretion rates were further reduced. Alterations in pHa alone or in PaCO2 had no significant effect. These results indicate that hypoxia is the principal factor responsible for the inhibition of lung liquid secretion during asphyxia and that acidaemia enhances this inhibition.

Acids↗

PubMed1996

Role of the adrenal glands in the maturation of lung liquid secretory mechanisms in fetal sheep.

Our aim was to determine the role of the fetal adrenal glands in the gestational age-related increase in the ability of epinephrine to induce the reabsorption of lung liquid. Fetal lung liquid volumes and secretion rates were measured in five chronically catheterized control and six bilaterally adrenalectomized (ADX) fetal sheep at approximately 5-day intervals from 120 to 144 days of gestation (term approximately 146 days). The ability of epinephrine to induce the reabsorption of fetal lung liquid was then determined on day 144. Fetal adrenalectomy prevented the preparturient increase in fetal plasma cortisol and 3,5,3'-triiodothyronine (T3) concentration and significantly reduced the gestational age-related increase in fetal lung liquid volumes and secretion rates. Close to term (144 days), epinephrine infusions caused a significantly greater rate of lung liquid reabsorption in control (32.2 +/- 4.8 ml/h) compared with ADX (3.7 +/- 0.7 ml/h) fetuses. We conclude that the presence of the fetal adrenal glands is necessary for the age-related increase in 1) the lung liquid secretion rate and 2) the ability of the fetal lung to reabsorb liquid late in gestation. It is likely that cortisol is the active adrenal hormone involved, supporting the theory that cortisol plays a crucial role in the clearance of lung liquid at birth.

Adrenal Glands↗

PubMed1996

Regulation of lung expansion and lung growth before birth.

Fetal lung growth depends on the degree to which lungs are distended with luminal liquid. Fetal lungs are highly distended such that mean luminal volume exceeds the static relaxation volume. This high level of expansion is maintained by fetal breathing movements and by resistive effects of the upper airway during apnea; both factors oppose lung recoil. Mechanical stress in lung and other tissues stimulates cell division and tissue remodeling. Potential transduction mechanisms involve direct effects of cellular tension and mediation of locally released mitogenic factors. Further studies are required to further define links between lung tissue stress, increased growth, structural remodeling, and the endocrine environment. A common cause of fetal lung hypoplasia is a sustained reduction in mean lung expansion. Studies of mechanisms controlling fetal lung expansion have led to insights into the etiology of fetal lung hypoplasia and how it may be remedied in utero. Fetal lung hypoplasia can have long-lasting effects on postnatal lung function, as airway and alveolar formation may be compromised. Preterm birth may also result in incomplete structural development of the lungs as it shortens the period of increased intrauterine lung expansion.

Animals↗

PubMed1995

Fetal metabolic responses to hypoxia.

It has been known for may years that hypoxaemia in the fetus induces a number of biophysical, cardiovascular, endocrine and metabolic responses by the fetus, some of which are not sustained if the period of hypoxaemia is extended. For instance, fetal breathing and body movements and the circulating concentrations of many of the stress-related hormones return to control levels during prolonged periods of hypoxaemia. In particular, circulating fetal blood glucose concentrations gradually return to control levels, after an initial increase. The initial increase is primarily due to a catecholamine-mediated increase in glucose production from glycogen stores leading to a marked reduction in glycogen content. During prolonged periods of hypoxaemia, however, the decrease in fetal blood glucose concentrations is principally due to a decrease in the activity of the major enzymes responsible for glycogenolysis and not to a total depletion of glycogen stores. It is suggested that the decrease in enzyme activity could be due to a prostaglandin E2-mediated antagonism of catecholamine-activated glycogenolysis. In contrast, fetal blood lactate concentrations increase to a plateau after 4-5 h of hypoxaemia and remain at this elevated level for the duration of the hypoxaemia. Circulating lactate concentrations do not increase further, despite production by hypoxic tissues remaining high, due to an increase in lactate clearance by the placenta; under normal conditions the placenta releases lactate into the fetal circulation. It is considered that many of these changes are important adaptive responses which allow the fetus to survive in a sub-optimal intrauterine environment.

Dinoprostone↗

PubMed1995

Fetal lung liquid: a major determinant of the growth and functional development of the fetal lung.

1. During fetal life the lung develops as a liquid-filled organ. This liquid is produced by the fetal lung and leaves via the trachea from where it is either swallowed or enters the amniotic sac. Fetal lung liquid plays a crucial role in the growth and development of the lungs by maintaining them in a distended state. It is now recognized that the retention of liquid within the future airways is required to maintain the lungs at an appropriate level of expansion in order to stimulate their growth. Indeed, it is likely that most, if not all, of the conditions and malformations that lead to inadequate growth of the fetal lung do so by reducing the volume of lung liquid and hence the degree of lung expansion. 2. The volume of fetal lung liquid is principally regulated by the resistance to lung liquid efflux through the fetal upper airway and by the presence of diaphragmatic activity associated with fetal breathing movements (FBM). During non-breathing periods, the relatively high resistance offered by the upper airway to the efflux of lung liquid opposes the loss of liquid from the lung, thereby maintaining fetal lung expansion. During episodes of FBM, when the larynx is actively dilated and the resistance to lung liquid efflux is reduced, lung liquid leaves the lungs at an increased rate. However, selective inhibition of diaphragmatic muscle activity in the foetus leads to a reduction in lung liquid volume, rather than an increase. This finding indicates that during periods of FBM, rhythmical contractions of the diaphragm retard the loss of lung liquid and help to maintain lung expansion when the upper airway resistance is reduced. It is now apparent that the maintenance of lung expansion by FBM is the basis for their role in promoting fetal lung growth. 3. Successful transition from intra-uterine to extra-uterine life is dependent upon the clearance of liquid from the fetal lungs at the time of birth so that the lungs may effectively function as an organ of gas exchange.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

PubMed1995

Effect of prolonged catecholamine infusion on heart rate, blood pressure, breathing, and growth in fetal sheep.

Norepinephrine and epinephrine were infused into fetal sheep for 24 h to compare the effects on fetal heart rate, blood pressure, breathing movements, and tissue growth with those of prolonged reductions in uterine blood flow. Norepinephrine concentrations increased (p < 0.01) from 871 +/- 71 to 6831 +/- 1090 pg/mL (2 h) with norepinephrine infusion, and epinephrine concentrations increased from 310 +/- 95 to 1424 +/- 288 pg/mL (2 h) with epinephrine infusion. Fetal pH decreased (p < 0.01) from 7.37 +/- 0.01 to 7.29 +/- 0.02 at 0.5 h of the norepinephrine infusion and returned to control values by 2 h, whereas fetal lactate concentrations increased (p < 0.05) from 1.6 +/- 0.2 to 4.6 +/- 1.0 mmol/L at 2 h and remained elevated for 12 h. Lactate concentrations also increased with epinephrine infusion. Fetal heart rate increased (p < 0.05) from 176 +/- 5 to 246 +/- 6 and 220 +/- 6 beats/min in the 1st h of norepinephrine and epinephrine infusions, respectively, with a subsequent decline. Fetal blood pressure increased (p < 0.05) from 43 +/- 3 and 40 +/- 2 to 53 +/- 3 and 47 +/- 2 mmHg (1 mmHg = 133.3 Pa) during the 1st h of norepinephrine and epinephrine infusions, respectively, remaining elevated for 24 h. Fetal body weights were not different between the groups of animals, although liver/body weight ratio was less (p < 0.05) in epinephrine-infused fetuses (0.030 +/- 0.001) compared with vehicle-infused animals (0.036 +/- 0.002). There was no change in DNA synthesis rate in any of the fetal organs, despite changes in organ-specific DNA and protein content. Our results indicate that the changes in fetal cardiovascular and behavioural function, as well as tissue growth, that occur with prolonged reductions in uterine blood flow are not mediated solely by elevated circulating catecholamine concentrations.

Adrenal Glands↗

PubMed1995

Oxygen, glucose, and lactate uptake by fetus and placenta during prolonged hypoxemia.

Our aim was to compare the effects of short (4 h) and prolonged (24 h) periods of reduced uterine blood flow (RUBF) on fetal and placental uptake of O2, glucose, and lactate. In pregnant sheep, uterine and umbilical blood flows were measured under normal conditions and after 4 and 24 h of RUBF. A 50% reduction in uterine blood flow caused a 56% reduction in fetal arterial O2 saturation (SaO2). Umbilical blood flow increased from 325 +/- 33 to 378 +/- 32 ml.min-1.kg-1 (P < 0.05) after 4 h but was not different from pre-RUBF values after 24 h. O2 uptake by the gravid uterus was not altered by RUBF, due to an increase (84%) in uterine O2 extraction. Similarly, uteroplacental and fetal O2 consumptions and fetal glucose uptake were not affected by RUBF, whereas uteroplacental glucose uptake was significantly reduced after 4 h (by 42%) and 24 h (by 58%) of RUBF. Fetal lactate uptake was greatly reduced from 78.7 +/- 15.5 to -167 +/- 57 mumol.min-1.kg-1 after 4 h and to -198 +/- 80 mumol.min-1.kg-1 after 24 h of RUBF; negative values indicate placental lactate uptake from the fetal circulation. Thus, although RUBF significantly reduced fetal SaO2, fetal and uteroplacental O2 consumptions did not change. In addition, although fetal glucose uptake was not altered by RUBF, during RUBF the placenta became a major site of lactate clearance from the fetal circulation.

Animals↗

PubMed1995

Effects of elevated fetal cortisol concentrations on the volume, secretion, and reabsorption of lung liquid.

We have examined the role of cortisol in the gestational age-related increase in the ability of epinephrine to inhibit the secretion and induce the reabsorption of fetal lung liquid. Chronically catheterized fetal sheep were infused with either saline (n = 6) or increasing doses of cortisol (1.5-3.5 mg/day; n = 6) between 120 and 130 days of gestation (term approximately 145 days). Lung liquid volumes and secretion rates were measured at 120 days (before infusion) and at 125 days, and then at 130 days we tested the ability of epinephrine to inhibit lung liquid secretion and induce liquid reabsorption. Cortisol infusions increased fetal plasma cortisol and 3,5,3'-triiodothyronine (T3) concentrations to levels observed just before labor and significantly increased the age-related increase in fetal lung liquid volume and secretion rate. At 130 days, epinephrine caused a significantly greater rate of lung liquid reabsorption in cortisol-infused fetuses (10.3 +/- 2.3 ml/h) than in saline-infused fetuses (1.5 +/- 1.6 ml/h). We conclude that a premature elevation in circulating fetal cortisol concentrations, probably in conjunction with elevated T3 concentrations, prematurely increases the epinephrine-induced reabsorption of fetal lung liquid. It is likely, therefore, that the preparturient increase of fetal cortisol concentrations plays an important role in the clearance of lung liquid at birth.

Absorption↗

PubMed1995

Endocrine responses of fetal sheep to prolonged hypoxemia with and without acidemia: relation to urine production.

Our aim was to examine the endocrine changes associated with alterations in fetal urine production during 24 h of hypoxemia induced by either reduced uterine blood flow (RUBF) or maternal N2 inhalation (N2). In contrast to RUBF, which caused a diuresis, N2 caused a transient antidiuresis; during both posthypoxemia periods (RUBF and N2), fetal urine production was increased. RUBF, but not N2, was associated with a transient acidemia. Fetal plasma arginine vasopressin (AVP) and atrial natriuretic factor (ANF) concentrations increased during RUBF and were inversely correlated to pH; there were no detectable AVP or ANF responses to N2. Fetal prostaglandin E2 (PGE2) increased during the hypoxemia and posthypoxemia periods induced by both methods, but RUBF caused the greater increase. AVP and PGE2 concentrations were positively correlated with urine production. Fetal arterial blood pressure increased during RUBF but not N2. During RUBF, the increases in AVP and PGE2 concentrations and/or fetal arterial blood pressure may have contributed to the diuresis. During N2, we suggest that low, but increased, levels of AVP may have caused the transient antidiuresis, whereas the diuresis observed during both posthypoxemia periods may have been mediated by elevated PGE2 concentrations and/or increased fetal arterial blood pressure.

Acids↗

PubMed1995

Lung hypoplasia can be reversed by short-term obstruction of the trachea in fetal sheep.

Our aim was to determine whether an existing lung growth deficit could be reversed, in utero, by short-term (6 d) obstruction of the fetal trachea. Chronically catheterized fetal sheep (term approximately 145 d) were divided into four groups: 1) no treatment (control); 2) continuous lung liquid drainage to induce lung hypoplasia (105-134 d, drain); 3) lung liquid drainage to induce lung hypoplasia (105-128 d), followed by restoration of tracheal flow (128-134 d, drain and reconnect); and 4) lung liquid drainage to induce lung hypoplasia (105-128 d), followed by tracheal occlusion to accelerate lung growth (128-134 d, drain and obstruct). Lung liquid volumes and secretion rates were measured on d 125, 130, and 134 of gestation and postmortem data collected on d 135. Compared with controls, continuous lung liquid drainage (drain) significantly reduced wet lung weights (34.3 +/- 2.6 g/kg versus 13.3 +/- 1.4 g/kg) and total lung DNA contents (177 +/- 11 mg/kg versus 94 +/- 7 mg/kg). Reestablishing tracheal flow for 6 d (drain and reconnect) increased fetal lung wet weights (19.2 +/- 1.6 g/kg), but not total DNA contents (106 +/- 9 mg/kg), compared with lung liquid drained fetuses (drain). After 6 d of tracheal obstruction (drain and obstruct) lung liquid volumes, wet lung weights, and total protein contents (weight, 28.6 +/- 2.8 g/kg; protein, 1376 +/- 97 mg/kg) were similar to control values (weight, 34.3 +/- 2.6 g/kg; protein, 1506 +/- 123 mg/kg); lung DNA contents were less than control but greater than values from lung liquid drained fetuses (drain and obstruct, 140 +/- 9 mg/kg versus drain, 94 +/- 7 mg/kg). We conclude that obstruction of the trachea can reverse an existing fetal lung growth deficit in approximately 6 d, whereas merely restoring tracheal continuity does not increase fetal lung growth.

Airway Obstruction↗

PubMed1994

The effects of twenty-four hours of reduced uterine blood flow on fetal fluid balance in sheep.

OBJECTIVE: Our aim was to determine the effects of a sustained reduction in uteroplacental perfusion, leading to fetal hypoxia, on determinants of amniotic fluid volume in sheep. STUDY DESIGN: Surgery was performed on five pregnant ewes 110 to 116 days after mating. At 127.3 +/- 2.2 days uterine blood flow was reduced for 24 hours, which reduced fetal SaO2 from 61.9% +/- 1.2% to 24.9% +/- 0.8%. RESULTS: Fetal urine production was increased from a control value of 193.0 +/- 24.0 ml/kg per 24 hours to 279.3 +/- 30.0 ml/kg per 24 hours during periods of reduced uterine blood flow and remained above control values for up to 48 hours after the reduced uterine blood flow period. A substantial loss of fetal water and electrolytes occurred through urine, which was associated with changes in the composition of fetal plasma and fetal tracheal, fetal swallowed, and amniotic fluids. Fetal swallowing was reduced throughout the reduced uterine blood flow period from a control value of 200.8 +/- 56.0 ml/kg per 24 hours to 32.7 +/- 8.4 ml/kg per 24 hours and returned to control levels after the cessation of the reduced uterine blood flow. CONCLUSION: We conclude that 24 hours of reduced uterine blood flow causes major changes in fetal renal function and fetal swallowing that, in spite of an expected reduction in lung liquid production, would increase the flow of fluid and electrolytes from the fetus into the amniotic sac.

Amniotic Fluid↗