Tracheal occlusion reverses the high impedance to flow in the fetal pulmonary circulation and normalizes its physiological response to oxygen at full term.
OBJECTIVE
The authors hypothesized that in utero tracheal occlusion would reverse the high impedance to pulmonary blood flow associated with congenital diaphragmatic hernia (CDH) and normalize the fetal physiological response to oxygen at term.


METHODS
Three experimental groups were studied. Six fetal lambs (CDH group) underwent creation of a left CDH at 80 days' gestation, an additional six fetal lambs underwent left CDH creation at 80 days' gestation followed by fetal tracheal occlusion performed at 108 days' gestation (CDH + TO group), and four control fetal lambs (control group) underwent a sham procedure at 80 days gestation. All lambs were followed up at 2-week intervals by pulse wave Doppler echocardiography. At each time-point the pulsatility index (PI) was calculated for the left branch pulmonary artery from the Doppler blood velocity waveform. Near term (term, 145 days gestation) at 136 days gestation, measurements were repeated under maternal normoxia and hyperoxia. The fetal lungs were harvested and processed for morphometric analysis by radial alveolar counts (RAC) and lung-to-body-weight ratios (LBWR) as measures of lung growth.


RESULTS
At 136 days' gestation the PI of the CDH + TO group (2.88 +/- 0.29) and control group (3.97 +/- 0.37) were significantly lower compared with the PI of the CDH group (9.02 +/- 0.50). There was a significant decrease in the PI of both the CDH + TO group and the control group with maternal hyperoxia at term, whereas the CDH group showed no change. The lungs of the CDH group fetuses were significantly smaller by LBWR and RAC than both CDH + TO and control fetuses.


CONCLUSIONS
An elevated PI is associated with pulmonary hypoplasia, fetal tracheal occlusion reverses this finding, and results in a normal fetal physiological response to changes in oxygen tension at term.
Center for Fetal Diagnosis and Treatment, The Children's Hospital of Philadelphia and The University of Pennsylvania School of Medicine, 19104, USA.
K G
KG
Sylvester
J
J
Rasanen
Y
Y
Kitano
A W
AW
Flake
T M
TM
Crombleholme
N S
NS
Adzick
D000704:Analysis of Variance; D000818:Animals; D001783:Blood Flow Velocity; D015150:Echocardiography, Doppler; D005314:Embryonic and Fetal Development; D005315:Fetal Diseases / Q000601:surgery*; D006439:Hemodynamics; D006548:Hernia, Diaphragmatic / Q000601:surgery*; D065630:Hernias, Diaphragmatic, Congenital; D008168:Lung / Q000098:blood supply / Q000196:embryology / Q000254:growth & development*; D009929:Organ Size; D011651:Pulmonary Artery / Q000196:embryology / Q000503:physiopathology*; D011673:Pulsatile Flow; D012756:Sheep; D014132:Trachea / Q000196:embryology / Q000601:surgery*