Relationship of structural to functional impairment during alveolar-capillary membrane development

Shawn K. Ahlfeld, Yong Gao, Simon Conway, Robert Tepper

Research output: Contribution to journalArticle

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Abstract

Bronchopulmonary dysplasia is a chronic lung disease of extreme preterm infants and results in impaired gas exchange. Although bronchopulmonary dysplasia is characterized histologically by alveolar-capillary simplification in animal models, it is clinically defined by impaired gas diffusion. With the use of a developmentally relevant model, we correlated alveolar-capillary structural simplification with reduced functional gas exchange as measured by the diffusing factor for carbon monoxide (DFCO). Neonatal mouse pups were exposed to >90% hyperoxia or room air during postnatal days 0 to 7, and then all pups were returned to room air from days 7 to 56. At day 56, DFCO was measured as the ratio of carbon monoxide uptake to neon dilution, and lungs were fixed for histologic assessment of alveolar-capillary development. Neonatal hyperoxia exposure inhibited alveolar-capillary septal development as evidenced by significantly increased mean linear intercept, increased airspace-to-septal ratio, decreased nodal density, and decreased pulmonary microvasculature. Importantly, alveolar-capillary structural deficits in hyperoxia-exposed pups were accompanied by a significant 28% decrease in DFCO (0.555 versus 0.400; P < 0.0001). In addition, DFCO was highly and significantly correlated with structural measures of reduced alveolar-capillary growth. Simplification of alveolar-capillary structure is highly correlated with impaired gas exchange function. Current mechanistic and therapeutic animal models of inhibited alveolar development may benefit from application of DFCO as an alternative physiologic indicator of alveolar-capillary development.

Original languageEnglish
Pages (from-to)913-919
Number of pages7
JournalAmerican Journal of Pathology
Volume185
Issue number4
DOIs
StatePublished - Apr 1 2015

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Carbon Monoxide
Membranes
Hyperoxia
Gases
Bronchopulmonary Dysplasia
Animal Models
Air
Neon
Lung
Microvessels
Premature Infants
Lung Diseases
Chronic Disease
Growth

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

Cite this

Relationship of structural to functional impairment during alveolar-capillary membrane development. / Ahlfeld, Shawn K.; Gao, Yong; Conway, Simon; Tepper, Robert.

In: American Journal of Pathology, Vol. 185, No. 4, 01.04.2015, p. 913-919.

Research output: Contribution to journalArticle

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