Sylvester K G, Rasanen J, Kitano Y, Flake A W, Crombleholme T M, Adzick N S
Center for Fetal Diagnosis and Treatment, The Children's Hospital of Philadelphia and The University of Pennsylvania School of Medicine, 19104, USA.
J Pediatr Surg. 1998 Jul;33(7):1071-4; discussion 1074-5. doi: 10.1016/s0022-3468(98)90533-4.
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.
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.
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.
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.
作者推测，子宫内气管闭塞可逆转与先天性膈疝（CDH）相关的肺血流高阻抗，并使足月胎儿对氧气的生理反应正常化。
研究了三个实验组。六只胎羊（CDH组）在妊娠80天时接受左侧CDH造模，另外六只胎羊在妊娠80天时接受左侧CDH造模，随后在妊娠108天时进行胎儿气管闭塞（CDH + TO组），四只对照胎羊（对照组）在妊娠80天时接受假手术。所有胎羊每隔2周通过脉冲波多普勒超声心动图进行随访。在每个时间点，根据多普勒血流速度波形计算左分支肺动脉的搏动指数（PI）。在妊娠136天接近足月时（足月为妊娠145天），在母体常氧和高氧条件下重复测量。采集胎儿肺并通过径向肺泡计数（RAC）和肺与体重比（LBWR）进行形态计量分析，作为肺生长的指标。
在妊娠136天时，CDH + TO组（2.88 +/- 0.29）和对照组（3.97 +/- 0.37）的PI显著低于CDH组（9.02 +/- 0.50）。足月时母体高氧时，CDH + TO组和对照组的PI均显著降低，而CDH组无变化。CDH组胎儿的肺通过LBWR和RAC测量明显小于CDH + TO组和对照组胎儿。
PI升高与肺发育不全有关，胎儿气管闭塞可逆转这一发现，并导致足月时胎儿对氧张力变化的生理反应正常化。
