scholarly journals Stimulation of Lung Growth by Tracheal Obstruction in Fetal Sheep: Relation to Luminal Pressure and Lung Liquid Volume

1998 ◽  
Vol 43 (2) ◽  
pp. 184-190 ◽  
Author(s):  
Laura Nardo ◽  
Stuart B Hooper ◽  
Richard Harding
Keyword(s):  
Liquid Volume ◽  
Lung Growth ◽  
Fetal Sheep ◽  
Tracheal Obstruction ◽  
Lung Liquid ◽  
Stimulation Of

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.

scholarly journals Influence of growth hormone on the lung growth response to tracheal obstruction in fetal sheep

2000 ◽  
Vol 278 (3) ◽  
pp. L453-L459 ◽  
Author(s):  
L. Nardo ◽  
I. R. Young ◽  
S. B. Hooper
Keyword(s):  
Growth Hormone ◽  
Dna Content ◽  
Fetal Lung ◽  
Control Group ◽  
Lung Growth ◽  
Lung Weight ◽  
Fetal Sheep ◽  
Tracheal Obstruction ◽  
Lung Expansion ◽  
Lung Liquid

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.

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

1997 ◽  
Vol 273 (6) ◽  
pp. L1126-L1131 ◽  
Author(s):  
Rochelle E. Boland ◽  
Laura Nardo ◽  
Stuart B. Hooper
Keyword(s):  
Intravenous Injection ◽  
Dna Content ◽  
Growth Response ◽  
Fetal Lung ◽  
Saline Infusion ◽  
Lung Growth ◽  
Fetal Sheep ◽  
Tracheal Obstruction ◽  
Lung Liquid ◽  
Secretion Rates

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.

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)

Upper airway resistances in fetal sheep: the influence of breathing activity

1986 ◽  
Vol 60 (1) ◽  
pp. 160-165 ◽  
Author(s):  
R. Harding ◽  
A. D. Bocking ◽  
J. N. Sigger
Keyword(s):  
Respiratory Muscles ◽  
Upper Airway ◽  
Late Gestation ◽  
Liquid Volume ◽  
Upper Respiratory Tract ◽  
Fetal Sheep ◽  
Lower Trachea ◽  
Upper Respiratory ◽  
Lung Liquid ◽  
Laryngeal Resistance

Fetal breathing movements (FBM) and lung liquid volume are known to affect lung development, but little is known about mechanisms controlling movement of liquid through the upper respiratory tract (URT). Therefore we measured resistances of the URT in 8 unanesthetized fetal sheep during late gestation while FBM were monitored from pressures in the lower trachea or from electromyogram of respiratory muscles. URT resistance to liquid flow toward the amniotic sac increased from 3.5 +/- 1.9 Torr X ml-1 X min during episodes of FBM to 21.1 +/- 5.7 Torr X ml-1 X min during apnea. Laryngeal resistance during apnea was greater (P less than 0.001) than supralaryngeal resistance in each of six fetuses in which URT resistance was partitioned. Fetal paralysis abolished the increase in laryngeal resistance to efflux that was previously related to the high-voltage electrocortical state and apnea. We were unable to quantify URT resistance to fluid movement toward the lungs because the larynx acted as a valve, permitting flow toward the lungs only in the presence of FBM. The supralaryngeal portion of the URT also apparently acts as a valve, normally preventing the entry of amniotic fluid into the pharynx. These findings help to explain our earlier observations that efflux of liquid from the fetal lungs is greater during episodes of FBM than during apnea.

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.

Reversible tracheal obstruction in the fetal sheep: Effects on tracheal fluid pressure and lung growth

1995 ◽  
Vol 30 (8) ◽  
pp. 1172-1177 ◽  
Author(s):  
Ezat Hashim ◽  
Jean-Martin Laberge ◽  
Moy-Fong Chen ◽  
Edmond W. Quillen
Keyword(s):  
Fluid Pressure ◽  
Lung Growth ◽  
Fetal Sheep ◽  
Tracheal Obstruction

scholarly journals Respiratory function in lambs after in utero treatment of lung hypoplasia by tracheal obstruction

1999 ◽  
Vol 87 (6) ◽  
pp. 2296-2304 ◽  
Author(s):  
M. G. Davey ◽  
S. B. Hooper ◽  
M. L. Tester ◽  
D. P. Johns ◽  
R. Harding
Keyword(s):  
Pulmonary Function ◽  
Respiratory Function ◽  
Minute Ventilation ◽  
Treated Group ◽  
Lung Hypoplasia ◽  
Control Group ◽  
Diffusing Capacity ◽  
Fetal Sheep ◽  
Tracheal Obstruction ◽  
Lung Liquid

Tracheal obstruction (TO) stimulates growth of hypoplastic lungs in the fetus, but there is little knowledge of subsequent postnatal respiratory function. We have determined the effectiveness of TO in fetal sheep with existing lung hypoplasia in restoring postnatal respiratory function. Lung hypoplasia was induced by lung liquid drainage from 112 days of gestation to term (∼148 days). We used an untreated group (ULH), a treated group (TLH) in which the trachea was obstructed for 10 days, and a control group. ULH lambs died within 4 h of birth. TLH lambs were hypoxic for the first week and were hypercapic at 2 days. Pulmonary diffusing capacity, gas volumes, and respiratory compliances were not different between control and TLH lambs. Minute ventilation was not different between the two groups; however, tidal volumes were lower and respiratory frequencies were higher in TLH lambs than in controls for 2 wk after birth. We conclude that 10 days of TO in the presence of initial lung hypoplasia prevents death at birth and returns most aspects of pulmonary function to normal by 1–2 wk after birth.

Enhanced ventricular pump function and decreased reservoir backflow sustain rise in pulmonary blood flow after reduction of lung liquid volume in fetal lambs

2014 ◽  
Vol 306 (4) ◽  
pp. R273-R280 ◽  
Author(s):  
Joseph J. Smolich
Keyword(s):  
Blood Flow ◽  
Right Ventricular ◽  
Pulmonary Blood Flow ◽  
Ductus Arteriosus ◽  
Liquid Volume ◽  
Flow Profile ◽  
Fetal Sheep ◽  
Pump Function ◽  
Time Flow ◽  
Lung Liquid

Although a reduction in lung liquid volume increases fetal pulmonary blood flow, the changes in central flow patterns that sustain this increased pulmonary perfusion are unknown. To address this issue, eight anesthetized late-gestation fetal sheep were instrumented with pulmonary trunk (PT), ductus arteriosus (DA), and left pulmonary artery (PA) micromanometer catheters and transit-time flow probes, with blood flow profile and wave intensity analyses performed at baseline and after withdrawal of lung liquid via an endotracheal tube. Reducing lung liquid volume by 19 ± 6 ml/kg (mean ± SD) augmented right ventricular power by 34% ( P < 0.001), with distribution of an accompanying increase in mean PT blood flow (245 ± 63 ml/min, P < 0.001) to the lungs (169 ± 91 ml/min, P = 0.001) and across the DA (77 ± 92 ml/min, P = 0.04). However, although PT and DA flow increments were confined to systole and were related to an increased magnitude of flow-increasing, forward-running compression waves, the rise in PA flow spanned both systole (108 ± 66 ml/min) and diastole (61 ± 32 ml/min). Flow profile analysis showed that the step-up in PA diastolic flow was associated with diminished PA diastolic backflow and accompanied by a lesser degree of diastolic right-to-left DA shunting. These data suggest that an increased pulmonary blood flow after reduction of lung liquid volume is associated with substantial changes in PT-DA-PA interactions and underpinned by two main factors: 1) enhanced right ventricular pump function that increases PA systolic inflow and 2) decreased PA diastolic backflow that arises from a fundamental change in PA reservoir function, thereby resulting in greater passage of systolic inflow through the lungs.

Alterations in lung expansion affect surfactant protein A, B, and C mRNA levels in fetal sheep

1999 ◽  
Vol 276 (2) ◽  
pp. L239-L245 ◽  
Author(s):  
A. Lines ◽  
L. Nardo ◽  
I. D. Phillips ◽  
F. Possmayer ◽  
S. B. Hooper
Keyword(s):  
Lung Tissue ◽  
Blot Analysis ◽  
Fetal Lung ◽  
Surfactant Protein ◽  
Mrna Levels ◽  
Lung Growth ◽  
Fetal Sheep ◽  
Protein Levels ◽  
Tracheal Obstruction ◽  
Lung Expansion

Obstruction of the fetal trachea is a potent stimulus for fetal lung growth, and it has been suggested that this procedure may be used therapeutically to reverse lung growth deficits in human fetuses with lung hypoplasia. However, little is known about the effects of increased lung expansion on other aspects of lung development. Our aim was to determine the effect of increased and decreased lung expansion on the mRNA levels encoding surfactant protein (SP) A, SP-B, and SP-C in ovine fetal lungs. Lung tissue samples were collected from fetuses exposed to 2, 4, or 10 days of increased lung expansion caused by tracheal obstruction. The mRNA levels for SP-A, SP-B, and SP-C were determined by Northern blot analysis with specific ovine cDNA probes; SP-A protein levels were determined by Western blot analysis. Compared with age-matched (128-day gestational age) control fetuses, SP-A, SP-B, and SP-C mRNA levels in fetal lung tissue were significantly reduced at 2 days of tracheal obstruction and remained reduced at 4 and 10 days. However, SP-A protein levels were not reduced at 2 days of tracheal obstruction, tended to be reduced at 4 days, and were almost undetectable at 10 days. In contrast to tracheal obstruction, 7 days of lung liquid drainage significantly increased SP-C, but not SP-A, mRNA levels in fetal lung tissue compared with age-matched control fetuses. Our results demonstrate that increases in fetal lung expansion, induced by obstruction of the fetal trachea, cause large simultaneous reductions in SP-A, SP-B, and SP-C mRNA levels in the fetal lung as well as a decrease in SP-A protein levels. These data suggest that expression of the genes encoding SPs in the fetal lung are specifically responsive to the degree of lung expansion.

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