Postnatal growth of lung parenchyma in the piglet: Morphometry correlated with mechanics

Mansell, Anthony L.; Collins, Margaret H.; Johnson, Eddie; Gil, Joan

doi:10.1002/ar.1092410113

Cited by 14 publications

(17 citation statements)

References 26 publications

(42 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In Table 3 we use data from our previous study (12) and the present study to document age-related changes in the lungs of normal and FGR sheep. It is known that thinning of the septal walls occurs as the lung matures (41). In this study we showed that septal thinning was completed before birth as no further thinning occurred after birth.…”

supporting

confidence: 51%

Fetal Growth Restriction Has Long-Term Effects on Postnatal Lung Structure in Sheep

et al. 2004

View full text Add to dashboard Cite

We have previously shown that fetal growth restriction (FGR) during late gestation in sheep affects lung development in the near-term fetus and at 8 wk after birth. In the present study, our aim was to determine the effects of FGR on the structure of the lungs at 2 y after birth; our hypothesis was that changes observed at 8 wk after birth would persist until maturity. FGR was induced in sheep by umbilicoplacental embolization, which was maintained from 120 d until delivery at term (approximately 147 d); birth weights of FGR lambs were 41% lower than in controls. At 2 y after birth, body and lung weights were not different, but there were 28% fewer alveoli and alveoli were significantly larger than in controls; hence there was a 10% reduction in the internal surface area relative to lung volume in FGR sheep compared with controls. The lungs of FGR sheep, compared with controls, had thicker interalveolar septa as a result of increased extracellular matrix deposition; the alveolar blood-air barrier was also thicker, largely because of an 82% increase in basement membrane thickness. These changes are qualitatively similar to those observed at 8 wk. Our data show that structural alterations in the lungs induced by FGR that were apparent at 8 wk were still evident at 2 y after birth, indicating that FGR may result in permanent changes in the structure of the lungs of the offspring and may affect respiratory health and lung aging later in life. Low birth weight as a result of FGR has been associated with an increased risk of morbidity and mortality during infancy (1, 2). It is likely that altered lung development may be a contributing factor as it has been shown that the risk of respiratory illness and the requirement for ventilatory support is increased in FGR infants (3, 4). Respiratory impairments may persist into later life because low birth weight children who were growth-restricted in utero (5, 6), as well as adults having low birth weights (7,8), have evidence of impaired lung function. At present, however, the structural basis for a relationship between FGR and later pulmonary dysfunction is poorly understood.The sheep is a suitable animal model in which to study the effects of FGR on lung development; it is a long-gestation species in which alveolar formation begins before birth (9), as in the human (10), and which reaches sexual maturity 6 mo after birth. Recently we found, in developing sheep, that fundamental aspects of respiratory function were impaired after FGR; FGR lambs were hypoxemic and hypercapnic soon after birth and had reduced pulmonary diffusing capacity and lung compliance up to 8 wk (11). In addition to these functional alterations, we found that FGR induced structural changes in lung parenchyma that were evident in the near-term fetus and became more pronounced at 8 wk after birth (12). In particular, the blood-air barrier and structure of interalveolar septa were affected after FGR. It is possible that structural

show abstract

supporting

confidence: 51%

Fetal Growth Restriction Has Long-Term Effects on Postnatal Lung Structure in Sheep

et al. 2004

View full text Add to dashboard Cite

show abstract

“…It is possible that the differences in native ECM content of various species are due, in part, to the whether the animals are quadruped or bipedal, as mode of ambulation impacts breathing mechanics (34). The observed species-dependent lung properties reported in this work corroborate findings in the literature, including differences in alveolar size and septal thickness (35-38); GAG, collagen, and elastin content (17, 39); matrix stiffness (40, 41), and alveolar cellular composition (42, 43). …”

Section: Discussionsupporting

confidence: 89%

Comparative biology of decellularized lung matrix: Implications of species mismatch in regenerative medicine

et al. 2016

View full text Add to dashboard Cite

Lung engineering is a promising technology, relying on re-seeding of either human or xenographic decellularized matrices with patient-derived pulmonary cells. Little is known about the species-specificity of decellularization in various models of lung regeneration, or if species dependent cell-matrix interactions exist within these systems. Therefore decellularized scaffolds were produced from rat, pig, primate and human lungs, and assessed by measuring residual DNA, mechanical properties, and key matrix proteins (collagen, elastin, glycosaminoglycans). To study intrinsic matrix biologic cues, human endothelial cells were seeded onto acellular slices and analyzed for markers of cell health and inflammation. Despite similar levels of collagen after decellularization, human and primate lungs were stiffer, contained more elastin, and retained fewer glycosaminoglycans than pig or rat lung scaffolds. Human endothelial cells seeded onto human and primate lung tissue demonstrated less expression of vascular cell adhesion molecule and activation of nuclear factor-κB compared to those seeded onto rodent or porcine tissue. Adhesion of endothelial cells was markedly enhanced on human and primate tissues. Our work suggests that species-dependent biologic cues intrinsic to lung extracellular matrix could have profound effects on attempts at lung regeneration.

show abstract

“…Pigs are born with well-developed lungs (404). Airspace expansion and septal thinning during the first postnatal week is associated with increased elastic recoil followed by vigorous septal subdivision and thickening (237,403). Quadruped primates (monkeys and baboons) possess a barrel-shaped thorax and an infracardiac lobe separating the heart from the diaphragm (337).…”

Section: Matching the Components Of Pulmonary Gas Transport And The Cmentioning

confidence: 99%

Lung Structure and the Intrinsic Challenges of Gas Exchange

Hsia

Hyde

Weibel

2016

Comprehensive Physiology

159

137

View full text Add to dashboard Cite

Structural and functional complexities of the mammalian lung evolved to meet a unique set of challenges, namely, the provision of efficient delivery of inspired air to all lung units within a confined thoracic space, to build a large gas exchange surface associated with minimal barrier thickness and a microvascular network to accommodate the entire right ventricular cardiac output while withstanding cyclic mechanical stresses that increase several folds from rest to exercise. Intricate regulatory mechanisms at every level ensure that the dynamic capacities of ventilation, perfusion, diffusion, and chemical binding to hemoglobin are commensurate with usual metabolic demands and periodic extreme needs for activity and survival. This article reviews the structural design of mammalian and human lung, its functional challenges, limitations, and potential for adaptation. We discuss (i) the evolutionary origin of alveolar lungs and its advantages and compromises, (ii) structural determinants of alveolar gas exchange, including architecture of conducting bronchovascular trees that converge in gas exchange units, (iii) the challenges of matching ventilation, perfusion, and diffusion and tissue-erythrocyte and thoracopulmonary interactions. The notion of erythrocytes as an integral component of the gas exchanger is emphasized. We further discuss the signals, sources, and limits of structural plasticity of the lung in alveolar hypoxia and following a loss of lung units, and the promise and caveats of interventions aimed at augmenting endogenous adaptive responses. Our objective is to understand how individual components are matched at multiple levels to optimize organ function in the face of physiological demands or pathological constraints.

show abstract

Postnatal growth of lung parenchyma in the piglet: Morphometry correlated with mechanics

Cited by 14 publications

References 26 publications

Fetal Growth Restriction Has Long-Term Effects on Postnatal Lung Structure in Sheep

Fetal Growth Restriction Has Long-Term Effects on Postnatal Lung Structure in Sheep

Comparative biology of decellularized lung matrix: Implications of species mismatch in regenerative medicine

Lung Structure and the Intrinsic Challenges of Gas Exchange

Contact Info

Product

Resources

About