Experimental fetal tracheal ligation prevents the pulmonary hypoplasia associated with fetal nephrectomy: Possible application for congenital diaphragmatic hernia

Wilson, Jay M.; DiFiore, John W.; Peters, Craig A.

doi:10.1016/0022-3468(93)90426-l

Cited by 202 publications

(85 citation statements)

References 25 publications

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“…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. In contrast, obstruction of the trachea in fetu ses with hypopl astic lung s quickl y increases the degree of lung expansion to normal levels, accelerat es lung growth and rever ses the lung growth deficit in as little as 6 d. Our findin gs support the recent observati ons that occlusion of the trach ea increases lung growth in fetal sheep with hypopl astic lung s indu ced by either herniation of the fetal diaph ragm (24) or nephrectomy (5) . In the experimentally indu ced diaphragm atic hern ia stud y (24), it was also show n that the increased lung expa nsion, caused by tracheal occlusion , succe ssfully displ aced abdomina l contents from the thorax (24) , which supports our previous prediction (4) .…”

Section: Methodssupporting

confidence: 87%

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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: Methodssupporting

confidence: 87%

“…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).…”

mentioning

confidence: 99%

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

1995

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“…Similar results were observed for the rescue of oligohydraneous fetal sheep and of fetal sheep with diaphragmatic hernias. The normally occurring hypoplasia was at least partly rescued due to a tracheal occlusion (33,34).…”

Section: Discussionmentioning

confidence: 99%

Spontaneous Peristaltic Airway Contractions Propel Lung Liquid through the Bronchial Tree of Intact and Fetal Lung Explants

Schittny

Miserocchi

Sparrow

2000

Am J Respir Cell Mol Biol

140

110

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Spontaneous contractions of the fetal airways are a well recognized but poorly characterized phenomenon. In the present study spontaneous narrowing of the airways was analyzed in freshly isolated lungs from early to late gestation in fetal pigs and rabbits and in cultured fetal mouse lungs. Propagating waves of contraction traveling proximal to distal were observed in fresh lungs throughout gestation which displaced the lung liquid along the lumen. In the pseudoglandular and canalicular stages (fetal pigs) the frequency ranged from 2.3 to 3.3 contractions/min with a 39 to 46% maximum reduction of lumen diameter. In the saccular stage (rabbit) the frequency was 10 to 12/min with a narrowing of ‫ف‬ 30%. In the organ cultures the waves of narrowing started at the trachea in whole lungs, or at the main bronchus in lobes (5.2 Ϯ 1.5 contractions/min, 22 Ϯ 8% reduction of lumen diameter), and as they proceeded distally along the epithelial tubes the luminal liquid was shifted toward the terminal tubules, which expanded the endbuds. Spontaneous narrowing and relaxation of the airways in the developing fetal lung has been described since the early part of the twentieth century. These spontaneous contractions are characteristic of phasic smooth muscle where regular bursts of action potentials give rise to rhythmic mechanical activity, typified by the smooth muscle of the viscera (1). Yet the contraction of mammalian airway smooth muscle in postnatal life is characterized by slow, graded contractions leading to airway narrowing and occurs without the generation of action potentials during membrane depolarization (2, 3). This is classified as tonic smooth muscle, in common with many blood vessels (1). Perhaps the rhythmic contractile activity of fetal airway smooth muscle is not so surprising since the intestine and the lung have a common embryological origin, with the lung developing as an outgrowth of the foregut in the late embryonic stage (4). Nevertheless, it indicates that airway smooth muscle would need to lose its capacity to generate spontaneous electrical activity sometime during fetal life or at birth and acquire the characteristics of tonic smooth muscle. If and when this occurs is unknown.The phenomenon of spontaneous narrowing of airways in the fetal lung was first observed in explants of lung in culture from embryos of chicken (5) and guinea pigs (6). More recently it was reported in explants of first-trimester human lung (7) and in gestation Day 11 mouse lung (8), where by 48 h in culture, spontaneous contractions began. However, much less information is available for intact fetal airways. McCray (7) noted spontaneous activity of epithelial tubules in small fragments of fresh lungs from first-trimester human fetuses and characterized their contractile responses to pharmacologic agents (discussed later). Sparrow and colleagues (9, 10) video-recorded sequences of strong spontaneous narrowing of individual airways in the isolated intact bronchial tree in the late first and early second trimesters of fetal pig l...

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“…Occlusion of the fetal trachea was shown to stimulate fetal growth in a variety of animal models [34][35][36][37][38][39][40]. On the other hand, prematurity caused by the intervention itself can be detrimental.…”

Section: Introductionmentioning

confidence: 99%

The long-term follow-up of patients with a congenital diaphragmatic hernia: a broad spectrum of morbidity

et al. 2008

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Congenital diaphragmatic hernia (CDH) is a life-threatening anomaly with a mortality rate of approximately 40-50%, depending on case selection. It has been suggested that new therapeutic modalities such as nitric oxide (NO), high frequency oxygenation (HFO) and extracorporal membrane oxygenation (ECMO) might decrease mortality associated with pulmonary hypertension and the sequelae of artificial ventilation. When these new therapies indeed prove to be beneficial, a larger number of children with severe forms of CDH might survive, resulting in an increase of CDH-associated complications and/or consequences. In follow-up studies of infants born with CDH, many complications including pulmonary damage, cardiovascular disease, gastro-intestinal disease, failure to thrive, neurocognitive defects and musculoskeletal abnormalities have been described. Long-term pulmonary morbidity in CDH consists of obstructive and restrictive lung function impairments due to altered lung structure and prolonged ventilatory support. CDH has also been associated with persistent pulmonary vascular abnormalities, resulting in pulmonary hypertension in the neonatal period.

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Experimental fetal tracheal ligation prevents the pulmonary hypoplasia associated with fetal nephrectomy: Possible application for congenital diaphragmatic hernia

Cited by 202 publications

References 25 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

Spontaneous Peristaltic Airway Contractions Propel Lung Liquid through the Bronchial Tree of Intact and Fetal Lung Explants

The long-term follow-up of patients with a congenital diaphragmatic hernia: a broad spectrum of morbidity

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