Respiratory Function in Lambs after Prolonged Oligohydramnios during Late Gestation

Jakubowska, Alexandra E; Billings, Kathleen R.; Johns, DP; Hooper, Stuart B.; Harding, Richard

doi:10.1203/00006450-199311000-00011

Cited by 17 publications

(12 citation statements)

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“…It is not surprising, therefore, that pulmonary hypopl asia persisted at birth after simul ated surgica l repair of a diaphragmatic hernia (22) . Furthermore, we sugges t that the failure of the hypoplastic lung to expand, in the absence of tracheal obstruction, is most probably the consequence of a relatively incompli ant lung and, perhaps more importantly, chest wall (23). Under these conditions, the normal resistance to lung liquid efflux offered by the upper airway (15,16) is prob ably insufficient to promote fluid accumulation and, therefore, increase lung expansion to the level required to stimulate lung grow th.…”

Section: Methodsmentioning

confidence: 96%

Lung Hypoplasia Can Be Reversed by Short-Term Obstruction of the Trachea in Fetal Sheep

1995

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i\HSTR,A T Vol. 38, No.5, 1995 Primed ill U.S.A.Our aim was 10 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 -145 d) were divided into four groups: 1) no treatment (control); 2) continuous lung liquid drainage to induce lung hypoplasia Th roughout mos t of gestation the lungs are filled with a liquid that is secreted across the pulmonary epithelium and leaves the lungs via the trachea. It is well established that the vo lume of liqu id retained wit hin the future airways is critical for normal lung growth and deve lopment. Obstruct ion of the feta l trach ea, wh ich causes secreted lung liquid to accumulate in the future airways resulting in increased expansion of the lungs (1) , greatly increases lung growth (2, 3). Conversely, prolonged drainage of feta l lung liqu id to the exterior causes lung deflation and a near cessation of lung grow th (2, 3). We have recently show n that the increase in lung growth induced by tracheal obstruction is ver y rapi d and occurs within 7 d of blocking the feta l trachea (4). Such results have led to the suggestion that short-term per iods of tracheal obstruct ion ma y rapi dly reverse an existing lung growth deficit in utero (4, 5).Inadequ ate lung growth during feta l life res ults in pul monary hypoplasi a at birth and is a common cause of perinatal mor- mg/kg versus 94 :t 7 mg/kg). Reestablishing tracheal flow for 6 d (drain and reconnect) increased fetal lung wet weights (19.2 :t 1.6 g/kg), but not total DNA contents (106 :t 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 :t 2.8 g/kg; protein, 1376 :t 97 mg/kg) were similar to control values (weight, 34.3 :t 2.6 g/kg; protein, 1506 :t 123 mg/kg); lung DNA contents were less than control but greater than values from lung liquid drained fetuses (drain and obstruct, 140 :t 9 mg/kg versus drain, 94 :t 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. (Pediatr Res 38: 690-69 6, 1995) bidity and mortality in new born infants (6, 7). To avoid the postnatal consequences of fetal lung hypoplasia in humans, atte mpts have been made to surgically treat this condition in utero, before the lungs are required for gas exchange. However, these treatments have principally foc used on correcting the und erlying abnormality rather than attempting to acce lerate lung growth directly (8, 9). As increased fe tal lung expansion, resulting from tracheal obstruction, is a potent and rapid way of accelerating fetal lung gro wth (2-4), we considered it possible tha t trac hea l obstruction may rapi dly reve rse an exi sting lung growth defici t in utero. The aim of this study was to determine whether fe tal lun...

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Section: Methodsmentioning

confidence: 96%

Lung Hypoplasia Can Be Reversed by Short-Term Obstruction of the Trachea in Fetal Sheep

1995

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“…Data on fetal lung liquid volumes from other species, including humans, are not available. The end-expiratory volume, or functional residual capacity (FRC), of the air-filled lung in newborn iambs during the first postnatal month is approximately 20-25 mL/kg (Roy et al Jakubowski et al 1993;Fig. la).…”

Section: Control Of Fetal Lung Liquid Volumementioning

confidence: 99%

Fetal Lung Liquid: A Major Determinant of the Growth and Functional Development of the Fetal Lung

Hooper

Harding

1995

Clin Exp Pharma Physio

240

176

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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)

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“…tracheo-amniotic shunt and amniotic fluid drainage) to induce a more severe LH than that induced by amniotic fluid alone. Previous studies in sheep have shown that drainage of amniotic fluid only induces a mild degree of lung hypoplasia [35,36]. At ~140 days of gestation, the ewes and fetuses were anaesthetized for implantation of fetal vascular catheters and a pulmonary artery flow probe; immediately after this, the fetuses were delivered and ventilated for two hours …”

Section: Our Recent Studies On the Neonatal Effects Of Fetal Lung Hypmentioning

confidence: 99%

Pulmonary Circulation and Pulmonary Function in Neonatal Lung Hypoplasia:Treatment with Corticosteroids

Suzuki¹,

Harding

2007

CPR

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Lung hypoplasia (LH) is a common neonatal problem resulting from small, structurally immature lungs. LH is a graded condition which, if severe, is life threatening due to impairment of ventilation, pulmonary blood flow and gas exchange. Although the effects of LH on the structure of lung parenchyma have been well defined in a number of species, little is known about its structural or functional effects on the pulmonary vasculature. Using an ovine model of bilateral LH we have studied pulmonary vascular development and blood flow in relation to ventilatory performance and lung mechanics. LH greatly increases pulmonary vascular resistance and is associated with evidence of impaired development of the pulmonary vasculature, and decreased mRNA levels of vascular growth factors such as PDGF and PECAM-1. Many studies have shown that antenatal corticosteroid treatment has a beneficial effect on lung development and the perinatal transition. In neonatal sheep with LH, lung compliance is not affected by a single dose of antenatal corticosteroids but pulmonary vascular resistance is significantly reduced, and mRNA expressions of PDGF and PECAM-1 normalised. It is clear that antenatal corticosteroids could be a promising treatment option for infants experiencing difficulties with perinatal adaptation of the pulmonary circulation associated with LH and other pathological respiratory conditions.

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Respiratory Function in Lambs after Prolonged Oligohydramnios during Late Gestation

Cited by 17 publications

References 0 publications

Lung Hypoplasia Can Be Reversed by Short-Term Obstruction of the Trachea in Fetal Sheep

Lung Hypoplasia Can Be Reversed by Short-Term Obstruction of the Trachea in Fetal Sheep

Fetal Lung Liquid: A Major Determinant of the Growth and Functional Development of the Fetal Lung

Pulmonary Circulation and Pulmonary Function in Neonatal Lung Hypoplasia:Treatment with Corticosteroids

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