Impaired structural remodelling of pulmonary arteries in newborns with congenital diaphragmatic hernia: a histological study of 29 cases

Shehata, Sherif M.; Tibboel, Dick; Sharma, Hari Shanker; Mooi, Wolter J.

doi:10.1002/(sici)1096-9896(199909)189:1<112::aid-path395>3.0.co;2-8

Cited by 64 publications

(40 citation statements)

References 31 publications

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“…However, the pulmonary arteries were reduced in size for the airways, making a defect in pulmonary artery development a possible etiology. In lung hypoplasia due to congenital diaphragmatic hernia, where there is a reduced number of airway generations, intrapulmonary artery size is normal relative to the airways and lung volume, but there is an increase in muscular wall and adventitia 16,17 . In renal agenesis, increased pulmonary artery size relative to lung volume has been described 18 .…”

Section: Discussionmentioning

confidence: 99%

Prenatal diagnosis of primary pulmonary hypoplasia in fraternal twins

Chen

Ursell

Adatia

et al. 2009

Ultrasound in Obstet & Gyne

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CASE REPORTA 38-year-old woman, gravida 2 para 1, was referred for fetal echocardiography for evaluation of abnormal cardiac axes in a set of twins. The woman had previously delivered a term male infant who died at 1 month of age from severe respiratory distress despite aggressive mechanical support. Autopsy revealed bilateral lung hypoplasia with arrested acinar development, small pulmonary arteries and a radial alveolar count of four. The couple was not consanguineous.The mother presented to our program at 18 weeks' gestation with dizygotic twins (female and male), products of in-vitro fertilization. General fetal ultrasound examination revealed a right-sided subependymal hemorrhage in the female, and mildly decreased thoracic circumference and normal amniotic fluid levels in both twins. Fetal echocardiography in both demonstrated normal cardiac anatomy and function. Both had a leftward cardiac axis (female, 90 • ; male, 80 • ) and an increased cardiothoracic diameter ratio (female, 60%; male, 50%), and the female had a small pericardial effusion (Figure 1). Both fetuses had hypoplastic branch pulmonary arteries (0.9-1.2 mm in female and 1.3-1.5 mm in male vs. 1.8 mm expected). Flow could not be demonstrated in the pulmonary arteries or pulmonary veins by color or pulsed Doppler imaging in either twin. The findings of hypoplastic branch pulmonary arteries with decreased flow and increased cardiothoracic diameter ratios suggested pulmonary hypoplasia. The parents requested elective termination of the pregnancy.The twins were delivered at 19 weeks' gestation, weighing 169 g (male) and 127 g (female). In both, the diaphragms were intact and there were no cardiac malformations, skeletal dysplasia or renal malformations. The lungs were normally configured but extremely small. In the male, the lungs weighed 1.6 g (expected 5.6 g). In the female, the lungs weighed 1.4 g. Both had markedly hypoplastic extrapulmonary branch pulmonary arteries.The lungs of each fetus showed similar histopathology: there was a lobular architecture with thickened connective tissue septa and prominent lymphatics. In contrast to cuboidal epithelium expected at this developmental stage, the distal sac epithelium of the twins appeared intermediate between columnar and cuboidal epithelium, with low columnar epithelium containing dark nuclei. There was a striking paucity of terminal airspaces within each lobule, and the mesenchymal interstitium was thicker than normal. Peripheral airways were larger than those observed in controls. The findings suggested persistent pseudoglandular stage. The cartilaginous airways were found closer to the pleura than normal, suggesting failure

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Section: Discussionmentioning

confidence: 99%

Prenatal diagnosis of primary pulmonary hypoplasia in fraternal twins

Chen

Ursell

Adatia

et al. 2009

Ultrasound in Obstet & Gyne

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“…Several studies have shown that under normal conditions, when approaching full term, pulmonary arteries show reduction in medial thickness [74][75][76]. Molecular basis underlying these changes in pulmonary vasculature during gestation are not known yet.…”

Section: Pulmonary Vasculaturementioning

confidence: 99%

“…The role of vascular smooth muscle cells appears to be crucial [77]. The physiologic reduction in medial thickness when approaching full term was not observed in CDH lungs [76][77][78]. Pulmonary vascular abnormalities in CDH consist of decreased number of pulmonary arteries per unit lung volume and an increase in the medial, adventitial and consequently total wall thickness of all arteries [4,45,[76][77][78][79][80][81].…”

Section: Pulmonary Vasculaturementioning

confidence: 99%

“…The physiologic reduction in medial thickness when approaching full term was not observed in CDH lungs [76][77][78]. Pulmonary vascular abnormalities in CDH consist of decreased number of pulmonary arteries per unit lung volume and an increase in the medial, adventitial and consequently total wall thickness of all arteries [4,45,[76][77][78][79][80][81]. Due to failure of vascular remodeling, peripheral muscularization of pulmonary arterioles resulted in particularly medial and adventitial thickening [15,78,79,81].…”

Section: Pulmonary Vasculaturementioning

confidence: 99%

“…All these factors together may predispose infants born with CDH for pulmonary hypertension [45,76,77].…”

Section: Ecmo and Pulmonary Vasculaturementioning

confidence: 99%

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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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Endothelin receptor expression in human lungs of newborns with congenital diaphragmatic hernia

Lagausie

Buys-Roessingh

Ferkdadji

et al. 2004

The Journal of Pathology

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Congenital diaphragmatic hernia (CDH) is a major cause of refractory respiratory failure in the neonatal period and is characterized by persistent pulmonary hypertension of the newborn (PPHN) and pulmonary hypoplasia. Endothelin-1 (ET-1) dysregulation may play a significant role in the pathophysiology of PPHN and ET-1 acts through binding to type A (ETA) and type B (ETB) receptors. Therefore, ETA and ETB receptor protein expression was studied using immunohistochemistry in 10 lung specimens obtained from newborns with CDH, and 4 normal lung specimens, in order to explore whether dysregulation of ETA and ETB expression contributes to PPHN. ETA and ETB mRNAs were then quantified using real-time RT-PCR in laser-microdissected pulmonary resistive arteries. In the lungs of newborns with CDH, immunohistochemistry of both ETA and ETB receptors demonstrated over-expression in the thickened media of pulmonary arteries. Using laser microdissection and real-time RT-PCR, higher levels of ETA and ETB mRNA were found in CDH pulmonary arteries than in controls: this increase was more pronounced for ETA mRNA. This study provides the first demonstration of ET-1 receptor dysregulation in association with structural alteration of pulmonary arteries in newborns with CDH and PPHN. This dysregulation preferentially affects the ETA receptor. These results suggest that dysregulation of ET-1 receptors may contribute to PPHN associated with CDH.

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Impaired structural remodelling of pulmonary arteries in newborns with congenital diaphragmatic hernia: a histological study of 29 cases

Cited by 64 publications

References 31 publications

Prenatal diagnosis of primary pulmonary hypoplasia in fraternal twins

Prenatal diagnosis of primary pulmonary hypoplasia in fraternal twins

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

Endothelin receptor expression in human lungs of newborns with congenital diaphragmatic hernia

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