The incidence and characteristics of neonatal irreversible lung dysplasia

Cassidy, Jane; Smith, Jon; Goldman, Allan; Haynes, Simon; Smith, E O; Wright, Chris; Haworth, Sheila G.; Davis, Peter J.; Firmin, Richard K.; Kasem, K; Davis, Carl

doi:10.1067/mpd.2002.126602

Cited by 33 publications

(18 citation statements)

References 4 publications

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“…The pulmonary phenotype closely resembles the pathological features of alveolar capillary dysplasia (ACD), an increasingly recognized cause of persistent pulmonary hypertension of the newborn. 22,23 The striking abnormalities in pulmonary vascular development in eNOS-deficient mice are consistent with the now well-accepted role of NO in angiogenesis in response to a variety of growth factors, most importantly VEGF. 2 There are two principle mechanisms by which VEGF contributes to blood vessel formation in the developing lung: vasculogenesis, which gives rise to the formation of capillaries from blood lakes; and angiogenesis, by which the more central vessels are generated, 24,25 including the arterial and arteriolar branches.…”

Section: Discussionmentioning

confidence: 49%

Defective Lung Vascular Development and Fatal Respiratory Distress in Endothelial NO Synthase-Deficient Mice

Han

Babaei

Robb

et al. 2004

Circulation Research

137

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Abstract-Endothelium-derived NO plays a critical role in the regulation of cardiovascular function and structure, as well as acting as a downstream mediator of the angiogenic response to numerous vascular growth factors. Although endothelial NO synthase (eNOS)-deficient mice are viable, minor congenital cardiac abnormalities have been reported and homozygous offspring exhibit high neonatal mortality out of proportion to the severity of these defects. The aim of the present report was to determine whether abnormalities of the pulmonary vascular development could contribute to high neonatal loss in eNOS-deficient animals. We now report that eNOS-deficient mice display major defects in lung morphogenesis, resulting in respiratory distress and death within the first hours of life in the majority of animals. Histological and molecular examination of preterm and newborn mutant lungs demonstrated marked thickening of saccular septae, with evidence of reduced surfactant material. Lungs of eNOS-deficient mice also exhibited a striking paucity of distal arteriolar branches and extensive regions of capillary hypoperfusion, together with misalignment of pulmonary veins, which represent the characteristic features of alveolar capillary dysplasia. We conclude that eNOS plays a previously unrecognized role in lung development, which may have relevance for clinical syndromes of neonatal respiratory distress. Key Words: nitric oxide Ⅲ angiogenesis Ⅲ surfactant Ⅲ respiratory distress syndrome Ⅲ alveolar capillary dysplasia N O is a multifaceted vasodilator that has also been shown to be an important regulator of vascular growth and remodeling. 1 NO has been implicated as a critical downstream mediator in the biological response to a variety of angiogenic growth factors, 2-5 mediating endothelial cell (EC) proliferation, 6 migration, 7 and vascular tube formation. 3 Adult eNOS-deficient mice (eNOS Ϫ/Ϫ ) exhibit marked defects in postnatal angiogenesis, 8 moderate systemic hypertension, 9 and mild elevation in pulmonary vascular resistance with an exaggerated pulmonary vasoconstrictor response to hypoxia. 10 Although eNOS Ϫ/Ϫ mice are viable, litter sizes are characteristically small, and these offspring exhibit minor abnormalities such as bicuspid aortic valve 11 and atrial septal defects. 12 eNOS is strongly expressed in rodent 13 and ovine 14 fetal lungs at mid to late gestation, in both vascular endothelial as well as airway epithelial cells, 15 consistent with a possible role in the regulation of pulmonary vasculature and airway development. However, to date there has been no direct evidence implicating NO in fetal lung development, although recently eNOS has been shown to be involved in compensatory hyperplasia of postnatal lung 16 and in preventing loss of alveolarization during neonatal exposure to hypoxia. 17 The paradox between the important role of NO in postnatal angiogenesis, yet the apparently normal embryonic vascular development in eNOS Ϫ/Ϫ animals could be explained by a high degree of redundancy, which often is as...

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Section: Discussionmentioning

confidence: 49%

Defective Lung Vascular Development and Fatal Respiratory Distress in Endothelial NO Synthase-Deficient Mice

Han

Babaei

Robb

et al. 2004

Circulation Research

137

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“…This was almost certainly an underestimate, as ACD/MPV was documented in 33% of babies who had full autopsy examinations (12). At least one additional report showed that ACD/MPV was found in the majority of infants with idiopathic PPHN who did not respond to ECMO (six of seven infants) (20).…”

Section: Treatmentmentioning

confidence: 99%

“…For several reasons, these case reports almost certainly underestimate the true prevalence of ACD/MPV. First, the definitive diagnosis of ACD/MPV currently depends on histological examination of lung tissue on autopsy or ante mortem lung biopsy, and neither of these diagnostic modalities is universally pursued in the setting of a critically ill or dying newborn (12). Second, many infants born with ACD/MPV have associated malformations in other organ systems that may allow the lung pathology to go undetected.…”

Section: Historical Perspectivementioning

confidence: 99%

Alveolar Capillary Dysplasia

Bishop

Stankiewicz

Steinhorn

2011

Am J Respir Crit Care Med

210

220

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“…Die CACD tritt überwiegend sporadisch auf. Cassidy et al [4] analysierten in England retrospektiv über einen Zeitraum von 3 Jahren 173 Neugeborene, die mittels extrakorporaler Membranoxygenierung (ECMO) behandelt wurden und fanden 9 Fälle einer irreversiblen Lungendysplasie, darunter 5 Fälle einer CACD.…”

Section: Diskussionunclassified

“…Die Literaturanalyse zeigt, das ein Großteil der betroffenen Neugeborenen mit CACD erst post mortem diagnostiziert wird [4,10].…”

Section: Diskussionunclassified