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

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.

1991 ◽  
Vol 70 (1) ◽  
pp. 293-299 ◽  
Author(s):  
K. A. Dickson ◽  
R. Harding

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)


1993 ◽  
Vol 265 (4) ◽  
pp. L403-L409 ◽  
Author(s):  
S. B. Hooper ◽  
V. K. Han ◽  
R. Harding

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.


1995 ◽  
Vol 269 (4) ◽  
pp. R881-R887 ◽  
Author(s):  
M. J. Wallace ◽  
S. B. Hooper ◽  
R. Harding

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.


1989 ◽  
Vol 257 (4) ◽  
pp. R705-R710 ◽  
Author(s):  
S. B. Hooper ◽  
R. Harding

The hypothesis tested in this study was that beta-adrenergic stimulation is responsible for the inhibition of fetal lung liquid production during moderate fetal asphyxia. In chronically catheterized fetal sheep, net lung liquid production rates were measured over three consecutive periods: a control period, a period of reduced uterine blood flow (RUBF) or epinephrine infusion, and periods of RUBF or epinephrine infusion in the presence of the beta-adrenergic receptor antagonist propranolol. The net production rate of fetal lung liquid was decreased from a mean control value of 7.7 +/- 1.0 to 1.5 +/- 0.4 ml/h (P less than 0.001) by RUBF; the administration of propranolol had no further effect on these liquid production rates (1.1 +/- 0.5 ml/h). In other experiments epinephrine infusion reduced the net production rate of fetal lung liquid from a mean control value of 7.2 +/- 1.4 to 1.7 +/- 1.8 ml/h (P less than 0.025); the addition of propranolol reversed this inhibition (secretion rate 6.1 +/- 1.4 ml/h, P less than 0.005). We conclude that the inhibition of fetal lung liquid production induced by moderate fetal asphyxia does not solely result from catecholamine stimulation of pulmonary beta-receptors.


1990 ◽  
Vol 69 (1) ◽  
pp. 127-135 ◽  
Author(s):  
S. B. Hooper ◽  
R. Harding

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.


1989 ◽  
Vol 67 (6) ◽  
pp. 2401-2407 ◽  
Author(s):  
K. A. Dickson ◽  
R. Harding

Reduced amniotic fluid volume often results in fetal lung hypoplasia. Our aim was to examine the effects of prolonged drainage of amniotic and allantoic fluids on lung liquid volume (Vl), secretion rate (Vs), and tracheal flow rate (Vtr) in fetal sheep. In five experimental animals, amniotic and allantoic fluids were drained from 107 to 135 days of gestation. The volume of fluid drained from the experimental animals was 411.8 +/- 24.4 ml/day (n = 140). In six control animals, amniotic fluid volume was 747.7 +/- 89.7 ml (n = 15). Wet and dry lung weights were 20-25% lower in experimental fetuses than in control fetuses. Fetal hemoglobin, O2 saturation, arterial PO2, pH, and hematocrit were unchanged by drainage. During the drainage period, Vl was up to 65% lower, Vs was up to 35% lower, and Vtr was up to 40% lower in experimental fetuses than in control fetuses. We conclude that prolonged drainage of amniotic and allantoic fluids decreases Vl, Vs, and Vtr in fetal sheep. These findings indicate that fetal lung hypoplasia associated with oligohydramnios may be the result of a prolonged reduction in Vl.


1984 ◽  
Vol 62 (1) ◽  
pp. 157-159 ◽  
Author(s):  
Sidney Cassin

Experiments were performed on seven anesthetized fetal sheep to evaluate involvement of metabolites of the cyclooxygenase system in lung liquid production. Rates of lung liquid production were determined by dye dilution technique using blue dextran. The control rate of formation of lung liquid in these preparations was 4.6 ± 0.55 mL∙kg−1∙h−1. Administration of indomethacin (1.85 mg/kg) intraarterially to fetuses resulted in a 60% decrease in the rate of formation of lung liquid. The present studies suggest an involvement of products of the cyclooxygenase system in controlling the rate of secretion of lung liquid in fetal animals.


1993 ◽  
Vol 74 (1) ◽  
pp. 111-115 ◽  
Author(s):  
S. B. Hooper ◽  
M. J. Wallace ◽  
R. Harding

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.


1986 ◽  
Vol 61 (6) ◽  
pp. 2266-2272 ◽  
Author(s):  
K. A. Dickson ◽  
J. E. Maloney ◽  
P. J. Berger

The volume of liquid in the fetal lung depends on the amount of liquid secreted across the pulmonary epithelium and the amount flowing through the trachea. Lung liquid volume (V1) and secretion rate Vs) were determined using an indicator-dilution technique, while tracheal flow rate (Vtr) was measured simultaneously with a bubble flowmeter. Least-squares regression analysis showed that in 10 chronically instrumented fetal lambs, V1 increased from 51.0 ml at 119 days to 104.6 ml at 135 days (V1 = -347.65 + 3.35 X days; 95% confidence limits on slope: 1.89–4.81) before declining to 70.2 ml at 142 days gestation (V1 = 768.8 – 4.92 X days; 95% confidence limits on slope: -2.55 to -7.30). Similarly Vs increased from 7.4 ml/h at 119 days to 16.8 ml/h at 133 days (Vs = -72.35 + 0.67 X days; 95% confidence limits on slope: 0.21–1.14), before declining to 7.1 ml/h at 142 days (Vs = 159.07 – 1.07 X days; 95% confidence limits on slope: -0.56 to -1.57). Vtr did not change significantly with gestation. We conclude that V1 increases until 135 days gestation, after which it falls substantially. This fall in volume, which occurs well before the onset of labor, results predominantly from the decline in Vs.


2000 ◽  
Vol 278 (3) ◽  
pp. L453-L459 ◽  
Author(s):  
L. Nardo ◽  
I. R. Young ◽  
S. B. Hooper

Obstructing the fetal trachea is a potent stimulus for fetal lung growth, but little is known about the factors that regulate this process. Our aim was to determine the role of growth hormone (GH) in regulating the increase in lung growth induced by obstruction of the trachea in fetal sheep. Twenty chronically catheterized fetal sheep, nine of which were hypophysectomized, were divided into four experimental groups: 1) control group ( n = 4), 2) a group in which the fetal trachea was obstructed for 3 days (3-day obstructed; n = 6), 3) a 3-day obstructed group in which the pituitary was removed [hypophysectomized (HX)] and the fetus was given maintenance infusions of ACTH, thyroxine, and human GH (hGH; HX hGH 3-day obstructed; n = 5), and 4) a HX 3-day obstructed group in which the fetus was given maintenance infusions of ACTH and thyroxine ( n = 5). Tracheal obstruction significantly increased fetal lung liquid volumes from 37.2 ± 3.2 ml/kg in control fetuses to 75.6 ± 9.0 ml/kg in 3-day obstructed fetuses, and the presence or absence of GH did not affect this increase. Similarly, the presence or absence of GH did not affect the increase in lung weight or protein content induced by 3 days of tracheal obstruction. However, in the absence of GH, 3 days of tracheal obstruction failed to increase total lung DNA content above unobstructed control values (107.9 ± 5.3 and 94.1 ± 7.0 mg/kg for control and HX 3-day obstructed groups, respectively). In contrast, 3 days of tracheal obstruction increased total lung DNA content to a similar extent in fetuses with an intact pituitary and HX fetuses that received GH replacement (126.0 ± 4.4 and 126.7 ± 4.0 mg/kg for 3-day obstructed and HX hGH 3-day obstructed groups, respectively). These data indicate that the absence of GH either abolishes or delays the acceleration in cell division caused by an increase in fetal lung expansion.


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