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


  • Funding sources: This work was supported by the European Commission in its 6th Framework (EuroSTEC; LSHC-CT-2006-037409) and the Flemish Government (Instituut voor Wetenschap en Technologie; IWT/ 070715). SM, PK and VB were provided a grant within the Marie Curie Early Stage Research Training Programme (MEST CT2005 019707). VB is further supported by a Marie Curie Reintegration Grant (PERG07-GA-2010-268330; FP7-PEOPLE-2010-RG). JD is the recipient of a ‵Fundamental Clinical Researcher' grant of the Fonds voor Wetenschappelijk Onderzoek Vlaanderen (
  • Conflicts of interest: None declared Note: use the same font size and style as for the author's affiliation.

Jan Deprest.

E-mail: Jan.Deprest@uzleuven.be



Prenatal tracheal occlusion (TO) promotes lung growth and is applied clinically in fetuses with severe congenital diaphragmatic hernia. Limited data are available regarding the effect of duration of TO on lung development. Our objective was to evaluate the effects of long (2 and 2.5 days) versus short (1 day) TO on lung development in rats with nitrofen-induced diaphragmatic hernia.


Nitrofen was administered on embryonic day (ED) 9 and fetal TO performed either on ED18.5, 19 or 20 (term = 22 days). Sham-operated and untouched littermates served as controls. On ED21, lungs were harvested and only fetuses with a left-sided diaphragmatic defect were included in further analyses.


Lung–body-weight ratio incrementally increased with the duration of TO. Increased proliferation following long TO was confirmed by immunohistochemistry and qRT-PCR for the proliferation marker Ki-67. Irrespective of duration, TO induced more complex airway architecture. Medial wall thickness of pulmonary arteries was thinner after long rather than short TO.


In the nitrofen rat model of congenital diaphragmatic hernia, a longer period of TO leads to enhanced lung growth and less muscularized pulmonary arteries. © 2011 John Wiley & Sons, Ltd.