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

1995 ◽  
Vol 269 (4) ◽  
pp. R881-R887 ◽  
Author(s):  
M. J. Wallace ◽  
S. B. Hooper ◽  
R. Harding
Keyword(s):  
Plasma Cortisol ◽  
Fetal Lung ◽  
Liquid Volume ◽  
Fetal Sheep ◽  
Fetal Plasma ◽  
Age Related ◽  
Lung Liquid ◽  
Secretion Rates ◽  
Related Increase

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.

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

1996 ◽  
Vol 270 (1) ◽  
pp. R33-R40 ◽  
Author(s):  
M. J. Wallace ◽  
S. B. Hooper ◽  
R. Harding
Keyword(s):  
Gestational Age ◽  
Adrenal Glands ◽  
Fetal Lung ◽  
Fetal Sheep ◽  
Fetal Plasma ◽  
Age Related ◽  
Lung Liquid ◽  
Secretion Rates ◽  
Related Increase

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.

Regulation of lung liquid secretion by arginine vasopressin in fetal sheep

1990 ◽  
Vol 258 (1) ◽  
pp. R104-R111 ◽  
Author(s):  
M. J. Wallace ◽  
S. B. Hooper ◽  
R. Harding
Keyword(s):  
Gestational Age ◽  
Arginine Vasopressin ◽  
Plasma Cortisol ◽  
Fetal Lung ◽  
Inhibitory Effect ◽  
Fetal Sheep ◽  
Fetal Plasma ◽  
Fetal Asphyxia ◽  
Lung Liquid ◽  
Secretion Rates

We have investigated the influence of gestational age on the inhibition of fetal lung liquid secretion by arginine vasopressin (AVP). In eight fetal sheep, lung liquid secretion rates were measured before and during infusion of AVP (300 mu.kg-1.h-1) at gestational ages between 110 and 148 days. During infusions, the concentration of AVP in fetal plasma increased from less than 8.7 +/- 0.2 pg/ml to 848.7 +/- 75.1 pg/ml. Fetal plasma epinephrine concentrations were not altered during AVP infusion. Infusions of AVP had no effect on fetal lung secretion before 135 days of gestation; they caused a 40.8% inhibition between 136 and 140 days, and at ages greater than 140 days induced an inhibition of 78.4%. In two ewes during labor, AVP infusion caused either a complete inhibition of secretion or reabsorption of lung liquid. The inhibitory effect of AVP increased in an exponential-like fashion with increasing gestational age and appeared to parallel the preparturient rise in fetal plasma cortisol concentrations. Our results indicate that AVP may be involved in the clearance of lung liquid at term and that AVP is unlikely to mediate the inhibitory effect of fetal asphyxia on lung liquid secretion, at least until after 135 days of gestation.

Role of fetal breathing movements in control of fetal lung distension

1993 ◽  
Vol 75 (6) ◽  
pp. 2711-2717 ◽  
Author(s):  
A. A. Miller ◽  
S. B. Hooper ◽  
R. Harding
Keyword(s):  
Fetal Lung ◽  
Liquid Volume ◽  
Fetal Breathing ◽  
Static Relaxation ◽  
Fetal Breathing Movements ◽  
Phrenic Nerves ◽  
Fetal Lungs ◽  
Lung Liquid ◽  
Secretion Rates

Our aim was to determine the role of fetal breathing movements (FBM) in the maintenance of fetal lung liquid volume. Experiments were performed in 14 chronically catheterized fetal sheep. FBM were selectively abolished for 48 h by the infusion of tetrodotoxin (TTX) onto the phrenic nerves of five fetuses. Lung liquid volumes and secretion rates were measured before each treatment, 46–48 h after the start of the TTX infusion, and 22–24 h after the end of the infusion. Blockade of the phrenic nerves reduced fetal lung liquid volumes from 27.6 +/- 1.9 to 21.8 +/- 2.6 ml/kg and increased lung liquid secretion rates from 3.8 +/- 0.6 to 6.2 +/- 1.1 ml.h-1.kg-1. Control experiments confirmed the lack of effect of TTX infused intravenously and saline infused intrapleurally on changes in fetal lung liquid volume and secretion rate. To measure the static relaxation volume of the fetal lung, in six fetuses we combined skeletal muscle paralysis with bypass of the upper airway for 48 h. This reduced fetal lung liquid volume from 39.1 +/- 3.1 to 23.0 +/- 2.5 ml/kg and increased lung liquid secretion rates from 4.1 +/- 0.7 to 5.8 +/- 0.9 ml.h-1.kg-1. This experiment demonstrates that the fetal lung is normally maintained at a level of expansion that is much greater than its static relaxation volume. We conclude that the volume of luminal liquid in the fetal lungs is dependent on the diaphragmatic contractions associated with FBM. Their effect is to resist the elastic recoil of the fetal lungs, thereby reducing the loss of liquid from the lungs via the trachea.

Amiloride blocks the inhibition of fetal lung liquid secretion caused by AVP but not by asphyxia

1993 ◽  
Vol 74 (1) ◽  
pp. 111-115 ◽  
Author(s):  
S. B. Hooper ◽  
M. J. Wallace ◽  
R. Harding
Keyword(s):  
Control Period ◽  
Fetal Lung ◽  
Inhibitory Effect ◽  
Luminal Surface ◽  
Na Channels ◽  
Inhibitory Effects ◽  
Fetal Sheep ◽  
Pulmonary Epithelial Cells ◽  
Lung Liquid ◽  
Secretion Rates

We have examined whether the activation of Na+ channels, located on the luminal surface of pulmonary epithelial cells, mediates the inhibitory effects of both arginine vasopressin (AVP) and moderate asphyxia on fetal lung liquid secretion. Lung liquid secretion rates were measured in chronically catheterized fetal sheep during AVP infusions and during periods of asphyxia with and without an Na+ transport blocker (amiloride; 10(-4) M) present in lung liquid. Lung liquid secretion rates were also measured during epinephrine infusions with amiloride present in lung liquid. These secretion rates were compared with measurements made during a preceding control period. Both asphyxia and an infusion of AVP significantly reduced the rate of secretion of fetal lung liquid from 8.4 +/- 1.5 and 18.0 +/- 3.7 to 3.6 +/- 1.0 (P < 0.01) and 5.5 +/- 2.1 ml/h (P < 0.01), respectively. The addition of amiloride to lung liquid did not reverse the inhibitory effects of asphyxia on lung liquid secretion (8.6 +/- 0.8 vs. 0.7 +/- 0.4 ml/h) but did block the inhibitory effects of both epinephrine (14.8 +/- 4.4 vs. 13.8 +/- 3.1 ml/h) and AVP (18.0 +/- 3.7 vs. 19.5 +/- 5.0 ml/h). The addition of amiloride to lung liquid during fetal normoxia did not significantly affect fetal lung liquid secretion rates (8.2 +/- 1.1 vs. 7.4 +/- 0.7 ml/h). We conclude that the inhibitory effect of AVP on fetal lung liquid secretion, like that of epinephrine, involves the activation of luminal surface Na+ channels, whereas the inhibitory effect of asphyxia does not.

Fetal breathing and pressures in the trachea and amniotic sac during oligohydramnios in sheep

1991 ◽  
Vol 70 (1) ◽  
pp. 293-299 ◽  
Author(s):  
K. A. Dickson ◽  
R. Harding
Keyword(s):  
Amniotic Fluid ◽  
Flow Rate ◽  
Pressure Fluctuations ◽  
Fetal Lung ◽  
Lung Hypoplasia ◽  
Liquid Volume ◽  
Fetal Sheep ◽  
Tracheal Pressure ◽  
Fetal Breathing ◽  
Lung Liquid

Oligohydramnios commonly leads to fetal lung hypoplasia, but the mechanisms are not fully understood. Our aim was to determine, in fetal sheep, the effects of prolonged oligohydramnios on the incidence and amplitude of tracheal pressure fluctuations associated with fetal breathing movements (FBM), on tracheal flow rate during periods of FBM (VtrFBM) and periods of apnea (Vtrapnea), on tracheal pressure relative to amniotic sac pressure, and on amniotic sac pressure relative to atmospheric pressure. In five sheep, oligohydramnios was induced by draining amniotic and allantoic fluids from 107 to 135 days of gestation (411.8 +/- 24.4 ml/day), resulting in fetal lung hypoplasia. In five control sheep, amniotic fluid volume was 732.3 +/- 94.4 ml. Oligohydramnios increased the incidence of FBM by 14% at 120 and 125 days and the amplitude of FBM by 30–34% at 120–130 days compared with controls. From 120 days onward, VtrFBM was 35–55% lower in experimental fetuses than in controls. Influx of lung liquid during FBM was 87% lower in experimental fetuses than in controls. Vtrapnea, tracheal pressure, and amniotic sac pressure were not significantly altered by oligohydramnios. Our tracheal flow rate data suggest that transient changes in lung liquid volume during periods of FBM and periods of apnea were diminished by oligohydramnios. We conclude that the primary factor in the etiology of oligohydramnios-induced lung hypoplasia is not an inhibition of FBM (as measured by tracheal pressure fluctuations) or a reduction in amniotic fluid pressure.(ABSTRACT TRUNCATED AT 250 WORDS)

Changes in lung expansion alter pulmonary DNA synthesis and IGF-II gene expression in fetal sheep

1993 ◽  
Vol 265 (4) ◽  
pp. L403-L409 ◽  
Author(s):  
S. B. Hooper ◽  
V. K. Han ◽  
R. Harding
Keyword(s):  
Gene Expression ◽  
Dna Synthesis ◽  
Fetal Lung ◽  
Liquid Volume ◽  
Mrna Levels ◽  
Pulmonary Tissue ◽  
Fetal Sheep ◽  
Tracheal Obstruction ◽  
Lung Expansion ◽  
Lung Liquid

Our aim was to determine the effect of short-term (7 days) alterations in fetal lung liquid volume on pulmonary DNA synthesis rates and insulin-like growth factor-II (IGF-II) mRNA levels. Fifteen chronically catheterized fetal sheep were divided into three groups. In one, the trachea was obstructed, in another lung liquid was drained by gravity, and the third group served as controls. After 7 days, [3H]thymidine was injected into each fetus and 8 h later fetal tissues were collected. Fetal lung-to-body weight ratios and total lung DNA contents were greatly increased in fetuses with tracheal obstruction compared with control fetuses, whereas the drainage of lung liquid did not affect these measurements. DNA synthesis rates in pulmonary tissue were significantly reduced from a mean control value of 153.3 +/- 25.1 disintegrations per minute (dpm)/microgram DNA to 57.2 +/- 8.6 dpm/microgram DNA by lung liquid drainage (P < 0.05) and were significantly increased to 236.0 +/- 24.0 dpm/microgram DNA by tracheal obstruction (P < 0.05). Following tracheal obstruction, lung IGF-II mRNA levels were increased to 177.0 +/- 18.2% (P < 0.05) of the mean value for control fetuses, whereas they were reduced to 56.1 +/- 7.1% of control in lung liquid-drained fetuses. We conclude that altering fetal lung expansion has a potent and rapid effect on pulmonary DNA synthesis and that this effect may, in part, be mediated by an alteration in IGF-II gene expression.

Changes in surfactant-associated protein mRNA profile in growth-restricted fetal sheep

1999 ◽  
Vol 276 (3) ◽  
pp. L459-L465 ◽  
Author(s):  
Robert Gagnon ◽  
Johnathan Langridge ◽  
Kevin Inchley ◽  
Jun Murotsuki ◽  
Fred Possmayer
Keyword(s):  
Fetal Growth ◽  
Fetal Growth Restriction ◽  
Plasma Cortisol ◽  
Fold Increase ◽  
Fetal Lung ◽  
Placental Insufficiency ◽  
Control Group ◽  
Fetal Sheep ◽  
Tissue Levels ◽  
Fetal Plasma

To test the hypothesis that chronic placental insufficiency resulting in fetal growth restriction causes an increase in fetal lung surfactant-associated protein (SP) gene expression, we embolized chronically catheterized fetal sheep ( n = 6) daily using nonradioactive microspheres in the abdominal aorta for 21 days (between 0.74 and 0.88 of gestation) until fetal arterial oxygen content was reduced by ∼40–50%. Control animals ( n = 7) received saline only. Basal fetal plasma cortisol concentration was monitored. At the end of the experiment, fetal lung tissues were collected, and ratios of tissue levels of SP-A, SP-B, and SP-C mRNA to 18S rRNA were determined by standard Northern blot analysis. Total DNA content of fetal lungs was reduced by 30% in the embolized group compared with control group ( P = 0.01). There was a 2.7-fold increase in fetal lung SP-A mRNA ( P< 0.05) and a 3.2-fold increase in SP-B mRNA ( P < 0.01) in the chronically embolized group compared with those in the control group. SP-A and SP-B mRNA tissue levels were highly correlated with the mean fetal plasma cortisol levels on days 20–21( r = 0.90, P < 0.01 for SP-A mRNA and r = 0.94, P < 0.01 for SP-B mRNA). SP-C mRNA tissue levels were not significantly affected by placental insufficiency. We conclude that fetal growth restriction due to placental insufficiency is associated with alterations in fetal lung SP, suggesting enhanced lung maturation that was highly dependent on the degree of increase in fetal plasma cortisol levels.

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

1996 ◽  
Vol 8 (3) ◽  
pp. 327 ◽  
Author(s):  
MJ Wallace ◽  
SB Hooper ◽  
GJ McCrabb ◽  
R Harding
Keyword(s):  
Fetal Lung ◽  
Inhibitory Effect ◽  
Secretion Rate ◽  
Fetal Blood ◽  
Fetal Sheep ◽  
Treatment Groups ◽  
Fetal Asphyxia ◽  
Lung Liquid ◽  
The Individual ◽  
Secretion Rates

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.

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

1997 ◽  
Vol 82 (3) ◽  
pp. 927-932 ◽  
Author(s):  
A. Lines ◽  
S. B. Hooper ◽  
R. Harding
Keyword(s):  
Production Rate ◽  
Fetal Lung ◽  
Liquid Volume ◽  
Production Rates ◽  
Entire Volume ◽  
Fetal Sheep ◽  
Uterine Muscle ◽  
Near Term ◽  
Lung Liquid ◽  
Labor Onset

Lines, A., S. B. Hooper, and R. Harding. Lung liquid production rates and volumes do not decrease before labor in healthy fetal sheep. J. Appl. Physiol. 82(3): 927–932, 1997.—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 (∼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 weighed 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 (∼222.5 ± 36.6 ml) must be cleared after the onset of labor.

Changes in lung liquid dynamics induced by prolonged fetal hypoxemia

1990 ◽  
Vol 69 (1) ◽  
pp. 127-135 ◽  
Author(s):  
S. B. Hooper ◽  
R. Harding
Keyword(s):  
Amniotic Fluid ◽  
Fetal Lung ◽  
Liquid Volume ◽  
Uterine Blood Flow ◽  
Fetal Sheep ◽  
Fetal Breathing Movements ◽  
Before And After ◽  
Normoxic Control ◽  
Lung Liquid ◽  
Liquid Dynamics

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

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