A longer tracheal occlusion period results in increased lung growth in the nitrofen rat model
Department of Obstetrics and Gynaecology, Division Woman and Child, University Hospital Gasthuisberg, Herestraat 49, Leuven, Belgium. Prenatal Diagnosis
(Impact Factor: 3.27).
01/2012; 32(1):39-44. DOI: 10.1002/pd.2881
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.
Available from: Katarina Vukojevic
- "ive phases of the cell cycle ( Bullwinkel et al . , 2006 ) . Previous studies showed that Ki - 67 is a reliable marker for proliferative activity in the lungs ( Thomas et al . , 1996 ) . However , data about proliferative role of Ki - 67 in the development of normal human lung are scarce , and the majority of studies used different animal models ( Beck et al . , 2012 ; McDougall et al . , 2011 ) . Only two studies on human fetus investigated the role of Ki - 67 during alve - olar cell differentiation ( Tebar et al . , 2001 ) and hypoplastic lungs ( Dzieniecka et al . , 2013 ) . As a member of the cysteine – aspartic acid protease ( caspase ) family , caspase - 3 plays a key role in the execution - p"
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ABSTRACT: Expression pattern of the Ki-67, caspase-3 and matrix metalloproteinases-9 (MMP-9) factors were immunohistochemically analyzed in 48 human fetal lungs from 12 to 40 weeks of gestation. The number of Ki-67 positive cells in the epithelium of canaliculare (88cells/mm(2)) and sacculare stage (93cells/mm(2)) were significantly higher than in the epithelium of pseudoglandular stage (12cells/mm(2)) (p=0.0008 vs. p=0.003). The number of Ki-67 positive cells in the mesenchyme of canaliculare stage (132cells/mm(2)) was significantly higher than in the mesenchyme of pseudoglandular stage (37cells/mm(2)) (p=0.001). The proliferation of mesenchymal cells was higher than the epithelial cells in all developmental stages, especially in the canaliculare stage (p=0.007). Similarly, the number of caspase-3 positive cells in the epithelium of canalicular stage (13cells/mm(2)) was significantly higher than in the epithelium of pseudoglandular stage (6cells/mm(2)) (p=0.002) with peaks in the conductive epithelium of canalicular stage. The number of caspase-3 positive cells in the mesenchyme of canaliculare stage (3cells/mm(2)) was significantly higher than in the mesenchyme of saccular stage (0cells/mm(2)) (p=0.05). There were no caspase-3 positive cells in the mesenchyme of pseudoglandular stage. However, unlike the Ki-67 expression, mesenchymal cells in comparison to epithelial cells express substantially less caspase-3 in all developmental stages. Up to the saccular stage, the expression of MMP-9 in mesenchymal cells showed a linear increase with most pronounced expression in that stage. The number of MMP-9 positive cells in the mesenchyme of canaliculare (20cells/mm(2)) and sacculare (39cells/mm(2)) stage were significantly higher than in the mesenchyme of pseudoglandular stage (12cells/mm(2)) (p=0.04 vs. p=0.004). The first epithelial cells that express MMP-9 were present only at the alveolar stage. Increased proliferation and apoptosis of the mesenchymal cells of canalicular stage is important for formation of definite structures within the stroma of the lung parenchyma. Although apoptosis in the epithelium is not pronounced as proliferation, it is important for thinning of the epithelium and consequent spread of respiratory tract. However in the saccular stage when mesenchyme disappears, MMP-9 expression is more important for primitive alveoli differentiation.
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Available from: Victoria R Cornelius
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ABSTRACT: To evaluate the mortality and morbidity of infants with congenital diaphragmatic hernia who had undergone fetal endoscopic tracheal occlusion (FETO) and whether this was influenced by premature birth.
The gestational age at delivery, lung-head ratio (LHR) pre and post FETO, neonatal outcomes, and respiratory, gastro-intestinal, neurological, surgical, and musculoskeletal problems at follow up of consecutive infants who had undergone FETO were determined. Elective reversal of FETO was planned at 34weeks of gestation.
The survival rate of the 61 FETO infants was 48%, with 84% delivered prematurely. Thirty-one delivered <35weeks of gestation. Their survival rate was 18%. Twenty-three of 24 infants who had emergency balloon removal were born <35weeks of gestation. Survival was related to gestational age at delivery (OR 0.55, 95% CI 0.420, 0.77, p<0.001) and the duration of FETO (OR 0.73, 95% CI 0.59, 0.91, p<0.005). Infants born prior to 35weeks of gestation compared to those born at≥35weeks required a longer duration of ventilation (median 45days versus 12days, p<0.001), and a greater proportion had surgery for gastro-oesophageal reflux (50% versus 9%, p=0.011).
These results emphasize the need to reduce premature delivery following FETO.
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