Effect of tracheal occlusion on peripheric pulmonary vessel muscularization in a fetal rabbit model for congenital diaphragmatic hernia

Roubliova, Xenia; Verbeken, Eric; Wu, Jun; Vaast, P.; Jani, Jacques; Deprest, Jan

doi:10.1016/j.ajog.2004.01.006

Cited by 58 publications

(59 citation statements)

References 31 publications

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“…High mortality rates despite increased prenatal diagnosis and advances in neonatal care (14) led to the development of fetal tracheal occlusion (TO), a prenatal therapy designed to remedy lung hypoplasia. In nitrofen-induced CDH rats and surgically induced CDH sheep and rabbits, TO prevents the egress of lung fluid, stimulates lung tissue stretch and cell proliferation (40), and ameliorates lung growth and morphology (49,66). However, prolonged TO induces an excess of alveolar type II epithelial cell transdifferentiation in CDH models (18,66).…”

mentioning

confidence: 99%

Increased TGF-β: a drawback of tracheal occlusion in human and experimental congenital diaphragmatic hernia?

Vuckovic

Herber-Jonat

Flemmer

et al. 2016

American Journal of Physiology-Lung Cellular and Molecular Phys

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Survivors of severe congenital diaphragmatic hernia (CDH) present significant respiratory morbidity despite lung growth induced by fetal tracheal occlusion (TO). We hypothesized that the underlying mechanisms would involve changes in lung extracellular matrix and dysregulated transforming growth factor (TGF)-β pathway, a key player in lung development and repair. Pulmonary expression of TGF-β signaling components, downstream effectors, and extracellular matrix targets were evaluated in CDH neonates who died between birth and the first few weeks of life after prenatal conservative management or TO, and in rabbit pups that were prenatally randomized for surgical CDH and TO vs. sham operation. Before tissue harvesting, lung tissue mechanics in rabbits was measured using the constant-phase model during the first 30 min of life. Human CDH and control fetal lungs were also collected from midterm onwards. Human and experimental CDH did not affect TGF-β/Smad2/3 expression and activity. In human and rabbit CDH lungs, TO upregulated TGF-β transcripts. Analysis of downstream pathways indicated increased Rho-associated kinases to the detriment of Smad2/3 activation. After TO, subtle accumulation of collagen and α-smooth muscle actin within alveolar walls was detected in rabbit pups and human CDH lungs with short-term mechanical ventilation. Despite TO-induced lung growth, mediocre lung tissue mechanics in the rabbit model was associated with increased transcription of extracellular matrix components. These results suggest that prenatal TO increases TGF-β/Rho kinase pathway, myofibroblast differentiation, and matrix deposition in neonatal rabbit and human CDH lungs. Whether this might influence postnatal development of sustainably ventilated lungs remains to be determined.

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mentioning

confidence: 99%

Increased TGF-β: a drawback of tracheal occlusion in human and experimental congenital diaphragmatic hernia?

Vuckovic

Herber-Jonat

Flemmer

et al. 2016

American Journal of Physiology-Lung Cellular and Molecular Phys

View full text Add to dashboard Cite

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“…In addition, TO promotes vascular growth and development, reducing the thickness of the muscular layer in pulmonary arteries in sheep, rabbit, and rat models of DH (10)(11)(12)(13)(14)(15). Our group demonstrated hemodynamic improvement in rabbit fetuses with DH following TO (16).…”

mentioning

confidence: 70%

“…The peak in small arteries (<30-μm diameter) localizes the highest resistance at the intra-acinary level (30)(31)(32). There is one other study showing these types of data in a graph, also obtained from the rabbit model (15). In their study, Roubliova et al did not find a peak in AMT, but a straight descending line from the smaller and thicker arteries to the wider ones with less resistance.…”

Section: Effects Of To In Cdh Do Not Correlatementioning

confidence: 85%

“…Mortality rate was 100% until we sought advice from one of the researchers publishing on this model (15,23,(33)(34)(35)(36). After his counseling, we achieved a success rate of 40% in the first fetal operation, the creation of a DH.…”

Section: Effects Of To In Cdh Do Not Correlatementioning

confidence: 98%

“…Its fetuses, however, are large enough to allow hemodynamic examination with a fine-power Doppler ultrasonography machine (16), unlike rat fetuses. This model of CDH has been validated and repeatedly used (15,(20)(21)(22)(23)(24).…”

Section: Variable Correlationsmentioning

confidence: 99%

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Airway and vascular maturation stimulated by tracheal occlusion do not correlate in the rabbit model of diaphragmatic hernia

et al. 2013

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Background:In animal models of congenital diaphragmatic hernia (CDH), tracheal occlusion (TO) has induced maturation of both airway spaces and vascular structures. Airway and vascular response to TO are assumed to occur in parallel. This study aims to describe and measure the relationship between airway and vascular maturation induced by TO. Methods: A rabbit model of CDH on gestational day (GD) 23 and TO on GD 28 (term = GD 31) has been used. Two study groups have been defined: DH (diaphragmatic hernia) and TO (DH treated with TO). Animals were collected on GD 30 and blood flow data of the pulmonary artery (pulsatility index (PI) and fractional moving blood volume) were ultrasonographically measured. Lung morphometry consisted of measurements of radial alveolar count (RAC) and arterial muscular thickness. results: Animals in the DH group (n = 9) had the worst hemodynamic parameters; their lungs were hypoplastic and had the thickest arterial muscular layer. Animals in the TO group (n = 10) had all these effects reversed. There were no correlations among hemodynamic, airway, and vascular parameters, except for RAC and PI (r = −0.528, P = 0.043). conclusion: Airway and vascular maturation after TO appear to be uncorrelated effects. TO could trigger several pathways that separately regulate airway and vascular responses.

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Tracheal occlusion: A review of obstructing fetal lungs to make them grow and mature

Khan¹,

Cloutier²,

Piedboeuf³

2007

American J of Med Genetics Pt C

108

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Fetal lung growth and functional differentiation are affected strongly by the extent that pulmonary tissue is distended (expanded) by liquid that naturally fills developing future airspaces. Methods that prevent normal egress of this lung fluid through the trachea magnify mechanical stretching of lung parenchymal cells, thereby promoting lung development. Indeed, experimental observations demonstrate that in utero tracheal occlusion (TO) performed on fetuses during the late canalicular-early saccular stage potently stimulates pulmonary growth and maturation. In this review, we present the four principle non-human animal models of TO/obstruction and discuss them in relation to their utility in elucidating lung development, in remedying congenital diaphragmatic hernia (CDH) as well as in investigating the stretching effects on growth and remodeling of the fine vasculature.

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Effect of tracheal occlusion on peripheric pulmonary vessel muscularization in a fetal rabbit model for congenital diaphragmatic hernia

Cited by 58 publications

References 31 publications

Increased TGF-β: a drawback of tracheal occlusion in human and experimental congenital diaphragmatic hernia?

Increased TGF-β: a drawback of tracheal occlusion in human and experimental congenital diaphragmatic hernia?

Airway and vascular maturation stimulated by tracheal occlusion do not correlate in the rabbit model of diaphragmatic hernia

Tracheal occlusion: A review of obstructing fetal lungs to make them grow and mature

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