A longer tracheal occlusion period results in increased lung growth in the nitrofen rat model

2011 ◽  
Vol 32 (1) ◽  
pp. 39-44 ◽  
Author(s):  
Veronika Beck ◽  
Marcus G. Davey ◽  
Steffi Mayer ◽  
Guy Froyen ◽  
Sebastiaan Deckx ◽  
...  
1999 ◽  
Vol 87 (2) ◽  
pp. 769-775 ◽  
Author(s):  
Yoshihiro Kitano ◽  
Paul Davies ◽  
Daniel von Allmen ◽  
N. Scott Adzick ◽  
Alan W. Flake

Prenatal tracheal occlusion (TO) consistently accelerates lung growth in the sheep model of congenital diaphragmatic hernia (CDH). However, significant variability in lung growth has been observed in early clinical trials of TO. We hypothesized that lung hypoplasia created at relatively late stages of lung development may not be equivalent to human CDH-induced lung hypoplasia, which begins early in gestation. To test this hypothesis, we performed TO in the rat model of nitrofen-induced CDH. Left-sided CDH was induced by administering 100 mg of nitrofen to timed pregnant rats on day 9 of gestation. On day 19 of gestation, four to five fetuses per dam underwent surgical ligation of the trachea. At death ( day 21.5), lungs from non-CDH (non-CDH group), left-CDH (CDH group), and trachea-occluded left-CDH fetuses (CDH-TO group) were harvested and compared by weight, DNA and protein content, and stereological morphometry. Wet and dry lung weight-to-body weight ratio, total lung DNA and protein contents, the volume of lung parenchyma, and the total saccular surface area of the CDH-TO group were significantly increased relative to the CDH group and were either greater than or comparable to the non-CDH controls. We conclude that TO accelerates lung growth and increases lung parenchyma in an early-onset model of CDH-induced lung hypoplasia.


1999 ◽  
Vol 21 (1) ◽  
pp. 65-76 ◽  
Author(s):  
Monique E. De Paepe ◽  
Brian D. Johnson ◽  
Konstantinos Papadakis ◽  
François I. Luks

2005 ◽  
Vol 18 (3) ◽  
pp. 155-164 ◽  
Author(s):  
T. Oshiro ◽  
Y. Asato ◽  
M. Sakanashi ◽  
T. Ohta ◽  
K. Sugahara

2002 ◽  
Vol 37 (7) ◽  
pp. 1007-1010 ◽  
Author(s):  
Alexander Dzakovic ◽  
Amir Kaviani ◽  
Russell W. Jennings ◽  
Jay M. Wilson ◽  
Dario O. Fauza

2018 ◽  
Vol 315 (6) ◽  
pp. L1028-L1041 ◽  
Author(s):  
Jose Luis Peiro ◽  
Marc Oria ◽  
Emrah Aydin ◽  
Rashika Joshi ◽  
Nichole Cabanas ◽  
...  

Congenital diaphragmatic hernia (CDH) occurs in ~1:2,000 pregnancies and is associated with substantial morbidity and mortality. Fetal tracheal occlusion (TO) is an emerging therapy that improves lung growth and reduces mortality, although substantial respiratory compromise persists in survivors. In this study, we used tracheal fluid in a fetal sheep model of CDH with TO for proteomic analysis with subsequent validation of findings in sheep lung tissue. We found that the proteomic profiles of CDH tracheal fluid was most similar to control lung and CDH/TO lung most similar to TO lung. Among 118 proteins altered in CDH, only 11 were reciprocally regulated in CDH/TO. The most significantly altered pathways and processes were cell proliferation, phosphatidylinositol 3-kinase/AKT/mammalian target of rapamycin signaling, inflammation, and microtubule dynamics. CDH suppressed and TO promoted cell proliferation and AKT-related signaling cascades. By Western blot analysis and immunohistochemistry, epithelial PCNA and phosphorylated AKT were decreased in CDH and increased in TO and CDH/TO lungs. The Wnt target Axin2 was decreased threefold in CDH lung compared with control without a significant increase in CDH/TO lung. Cilia-related pathways were among the most dysregulated with CDH lung having a nearly twofold increase in acetylated α-tubulin and a relative increase in the number of ciliated cells. While TO improves lung growth and patient survival in CDH, the procedure substantially alters many processes important in lung development and cell differentiation. Further elucidation of these changes will be critical to improving lung health in infants with CDH treated with TO.


2001 ◽  
Vol 90 (2) ◽  
pp. 493-500 ◽  
Author(s):  
Yoshihiro Kitano ◽  
Daniel Von Allmen ◽  
Masaki Kanai ◽  
Theresa M. Quinn ◽  
Paul Davies ◽  
...  

Prenatal tracheal occlusion (TO) has been shown to accelerate fetal lung growth, yet the mechanism is poorly understood. The goal of this study was to determine the relationship between fetal intratracheal pressure (Pitr) and fetal lung growth after TO. Fetal lambs underwent placement of an intratracheal catheter and a reference catheter at 115–120 days gestation (term, 145 days). Fetal Pitr was continuously controlled at three levels (high, 8 mmHg; moderate, 4 mmHg; low, 1 mmHg) by a servo-regulated pump. The animals were killed after 4 days, and the parameters of lung growth were compared. Lung volume (136.0 ± 16.7, 94.9 ± 9.7, 55.5 ± 12.4 ml/kg), lung-to-body weight ratio (6.31 ± 0.70, 4.89 ± 0.38, 3.39 ± 0.22%), whole right lung dry weight (3.01 ± 0.29, 2.53 ± 0.15, 2.07 ± 0.24 g/kg), right lung DNA (130.0 ± 11.3, 116.7 ± 8.6, 97.5 ± 10.9 mg/kg), and protein contents (1,865.5 ± 92.5, 1,657.6 ± 106.8, 1,312.0 ± 142.5 mg/kg) in high, moderate, and low groups, respectively, all increased in the moderate compared with the low group and increased further in the high compared with the moderate group. Morphometry confirmed a stepwise increase in the volume of respiratory region and alveolar surface area. We conclude that lung growth in the first 4 days after TO is closely correlated with fetal Pitr, offering additional evidence that an increase in lung expansion is one of the major factors responsible for TO-induced lung growth.


2000 ◽  
Vol 35 (2) ◽  
pp. 216-222 ◽  
Author(s):  
Yoshihiro Kitano ◽  
Alan W. Flake ◽  
Theresa M. Quinn ◽  
Masaki Kanai ◽  
Paul Davies ◽  
...  

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