Tracheal ligation does not correct the surfactant deficiency associated with congenital diaphragmatic hernia.
BACKGROUND
Experimental tracheal ligation (CDH + TL) has been shown to reverse the profound lung hypoplasia associated with congenital diaphragmatic hernia (CDH) and to normalize gas exchange. The aim of this study was to determine whether this experimental therapy would correct the surfactant deficiency present in the fetal lamb model of CDH.


METHODS
The CDH lamb model was created at 80 days' gestation, and tracheal ligation was performed at 110 days. At term, the lambs were delivered and were ventilated for 30 minutes. The lambs were killed, a pressure-volume curve performed, and the lungs lavaged to measure total phospholipid content. Finally, type II pneumocytes were isolated, and surfactant synthesis was assessed by the incorporation of tritiated choline into phosphatidylcholine.


RESULTS
CDH + TL resulted in a lung significantly larger than that of CDH alone. The lungs of the former also had better oxygenation and ventilation. However, lung compliance was reduced compared with controls. Total alveolar phospholipid was dramatically lower, with a decrease in the proportion of phosphatidylcholine present. Surfactant synthesis by the isolated type II pneumocyte was significantly impaired.


CONCLUSIONS
Occlusion of the fetal trachea produces a lung comparable in size to a normal control lung. However, broncheoalveolar lavage analysis shows a marked reduction in total phospholipid, with a decrease in surfactant synthesis by the type II pneumocyte. The normalization of gas exchange reported for this animal model may be only a transient phenomenon. Further studies are required to assess the impact of this surfactant deficiency on long-term lung function.
O'Toole
S J
SJ
Buffalo Institute of Fetal Therapy (BIFT), NY, USA.
Sharma
A
A
Karamanoukian
H L
HL
Holm
B
B
Azizkhan
R G
RG
Glick
P L
PL
D000818:Animals; D000831:Animals, Newborn; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D004195:Disease Models, Animal; D005260:Female; D006548:Hernia, Diaphragmatic / Q000473:pathology / Q000503:physiopathology / Q000601:surgery; D065630:Hernias, Diaphragmatic, Congenital; D008026:Ligation; D010743:Phospholipids / Q000378:metabolism; D011247:Pregnancy; D011650:Pulmonary Alveoli / Q000473:pathology; D011663:Pulmonary Surfactants / Q000172:deficiency* / Q000502:physiology; D015656:Respiratory Mechanics / Q000502:physiology; D012756:Sheep; D014132:Trachea / Q000473:pathology / Q000503:physiopathology / Q000601:surgery*
D010743:Phospholipids; D011663:Pulmonary Surfactants