Contractile properties of intralobar pulmonary arteries and veins in the fetal lamb model of congenital diaphragmatic hernia

Irish, Michael S.; Glick, Philip L.; Russell, James A.; Kapur, Pierina; Bambini, Daniel A.; Holm, Bruce A.; Steinhorn, Robin H.

doi:10.1016/s0022-3468(98)90675-3

Cited by 22 publications

(17 citation statements)

References 31 publications

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“…In rats with nitrofeninduced CDH, decreased pulmonary NOS3 gene expression (30) and activity (21) have been documented. Conversely, NOS does not seem to be altered in the fetal lamb with CDH because NOS is evidenced by immunohistochemistry in the MPA (19) and fourth-generation pulmonary arteries have identical basal and stimulated release of NO compared with control animals (15).…”

Section: Discussionmentioning

confidence: 92%

ET_A-receptor blockade and ET_B-receptor stimulation in experimental congenital diaphragmatic hernia

Thébaud

Forgues

Aigrain

et al. 2000

American Journal of Physiology-Lung Cellular and Molecular Phys

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The aim of this study was to assess the role of nitric oxide (NO) and endothelin (ET)-1 in the pathophysiology of persistent pulmonary hypertension of the newborn in fetal lambs with a surgically created congenital diaphragmatic hernia (CDH). The pulmonary vascular response to various agonists and antagonists was assessed in vivo between 128 and 132 days gestation. Age-matched fetal lambs served as control animals. Control and CDH lambs had similar pulmonary vasodilator responses to acetylcholine, sodium nitroprusside, zaprinast, and dipyridamole. The ET(A)-receptor antagonist BQ-123 caused a significantly greater pulmonary vasodilatation in CDH than in control animals. The ET(B)-receptor agonist sarafotoxin 6c induced a biphasic response, with a sustained pulmonary vasoconstriction after a transient pulmonary vasodilatation that was not seen in CDH animals. We conclude that the NO signaling pathway in vivo is intact in experimental CDH. In contrast, ET(A)-receptor blockade and ET(B)-receptor stimulation significantly differed in CDH animals compared with control animals. Imbalance of ET-1-receptor activation favoring pulmonary vasoconstriction rather than altered NO-mediated pulmonary vasodilatation is likely to account for persistent pulmonary hypertension of the newborn in fetal lambs with a surgically created CDH.

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Section: Discussionmentioning

confidence: 92%

ET_A-receptor blockade and ET_B-receptor stimulation in experimental congenital diaphragmatic hernia

Thébaud

Forgues

Aigrain

et al. 2000

American Journal of Physiology-Lung Cellular and Molecular Phys

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“…Thus the diaphragmatic defects associated with CDH are a primary defect and not a secondary result of lung malformation. The concept that the lung hypoplasia is in fact secondary to the diaphragmatic defect is supported by data from the surgically induced sheep model of CDH that clearly demonstrates that a hole in the posterolateral diaphragm results in marked lung underdevelopment because of the invasion of abdominal contents and abnormal fetal breathing movements (16,17,23,25). However, there is convincing evidence demonstrating that the teratogens used in the rodent CDH model can directly interfere with lung development (1,6,13,20).…”

Section: Discussionmentioning

confidence: 98%

Diaphragm defects occur in a CDH hernia model independently of myogenesis and lung formation

Babiuk

Greer

2002

American Journal of Physiology-Lung Cellular and Molecular Phys

102

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Congenital diaphragmatic hernia (CDH) is a significant clinical problem in which a portion of the diaphragmatic musculature fails to form, resulting in a hole in the diaphragm. Here we use animal models of CDH to test two hypotheses regarding the pathogenesis. First, the origin of the defect results from the malformation of the amuscular mesenchymal component of the primordial diaphragm rather than with the process of myogenesis. Second, the defect in the primordial diaphragmatic tissue is not secondary to defects in the developing lung. In c-met(-/-) mouse embryos, in which diaphragm muscle fibers do not form because of a defect in muscle precursor migration, the amuscular substratum forms fully. We show that a defect characteristic of CDH can be induced in the amuscular membrane. In Fgf10(-/-) mouse embryos that have lung agenesis we show that the primordial diaphragm does not depend on signals from lung tissue for proper development and that diaphragmatic malformation is a primary defect in CDH. These data suggest that the pathogenesis of CDH involves mechanisms fundamentally different from previously proposed hypotheses.

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“…These infants have a delay in lung development, including fewer bronchial branches and alveoli, retardation of alveolar development with the presence of more cuboidal cells, markedly thickened alveolar walls, increased interstitial tissue, reduced alveolar air spaces and gas‐exchange surface area, and an increased muscularity of the pulmonary vascular bed (Levin, 1978; George et al, 1987; Kluth et al, 1993; Chinoy et al, 2001). Animal models have demonstrated that lung and cardiac defects typical of CDH can result from mechanical factors secondary to thoracic herniation through the primary diaphragm defect (Hill et al, 1994; Wilcox et al, 1996; Irish et al, 1998; Correia‐Pinto et al, 2003). The hypoplasia of CDH‐affected lungs may not only result from progressive compression by the herniated abdominal organs into the chest but also from changes to the mechanical stretch that stimulates cell division and tissue remodeling (Hooper and Harding, 1995).…”

Section: Pathophysiology Of Cdhmentioning

confidence: 99%

Congenital diaphragmatic hernia: A retinoid‐signaling pathway disruption during lung development?

Gallot

Marceau

Coste

et al. 2005

Birth Defects Research

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Congenital diaphragmatic hernia (CDH) usually occurs sporadically. The prognosis remains poor, with a 50% perinatal mortality rate. Most deaths result from hypoxemia due to lung hypoplasia and abnormal development of pulmonary vasculature that results in persistent pulmonary hypertension. Our current understanding of the pathogenesis of CDH is based on an assumption linking herniation of abdominal viscera into the thorax with compression of the developing lung. Pulmonary hypoplasia, however, can also result from reduced distension of the developing lung secondary to impaired fetal breathing movements. Moreover, a nitrofen-induced CDH model shows that lung hypoplasia precedes the diaphragmatic defect, leading to a "dual-hit hypothesis." Recent data reveal the role of a retinoid-signaling pathway disruption in the pathogenesis of CDH. We describe the clinical and epidemiological aspects of human CDH, the metabolic and molecular aspects of the retinoid-signaling pathway, and the implications of retinoids in the development of the diaphragm and the lung. Finally, we highlight the existing links between CDH and disruption of the retinoid-signaling pathway, which may suggest an eventual use of retinoids in the treatment of CDH.

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Contractile properties of intralobar pulmonary arteries and veins in the fetal lamb model of congenital diaphragmatic hernia

Cited by 22 publications

References 31 publications

ET_A-receptor blockade and ET_B-receptor stimulation in experimental congenital diaphragmatic hernia

ET_A-receptor blockade and ET_B-receptor stimulation in experimental congenital diaphragmatic hernia

Diaphragm defects occur in a CDH hernia model independently of myogenesis and lung formation

Congenital diaphragmatic hernia: A retinoid‐signaling pathway disruption during lung development?

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Contractile properties of intralobar pulmonary arteries and veins in the fetal lamb model of congenital diaphragmatic hernia

Cited by 22 publications

References 31 publications

ETA-receptor blockade and ETB-receptor stimulation in experimental congenital diaphragmatic hernia

ETA-receptor blockade and ETB-receptor stimulation in experimental congenital diaphragmatic hernia

Diaphragm defects occur in a CDH hernia model independently of myogenesis and lung formation

Congenital diaphragmatic hernia: A retinoid‐signaling pathway disruption during lung development?

Contact Info

Product

Resources

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ET_A-receptor blockade and ET_B-receptor stimulation in experimental congenital diaphragmatic hernia

ET_A-receptor blockade and ET_B-receptor stimulation in experimental congenital diaphragmatic hernia