Papadakis K, De Paepe M E, Tackett L D, Piasecki G J, Luks F I
Department of Surgery, Brown University School of Medicine, Providence, Rhode Island, USA.
J Pediatr Surg. 1998 Jul;33(7):1030-7. doi: 10.1016/s0022-3468(98)90526-7.
The lungs of infants born with diaphragmatic hernia are hypoplastic, immature, and surfactant-deficient. Tracheal occlusion in utero, which is being proposed as antenatal treatment of diaphragmatic hernia by promoting compensatory lung growth, decreases surfactant production as well, through loss of type II pneumocytes. The authors studied whether temporary tracheal occlusion might cause 'catch-up' lung growth and maturation, without negative effects of prolonged tracheal occlusion on the surfactant system.
Diaphragmatic hernia was created in time-dated fetal lambs (65 to 75 days). At 108 days, the trachea was occluded with an embolectomy catheter (DH + TO, n = 6). After day 14, the balloon was deflated. Six congenital diaphragmatic hernia (CDH) fetuses were left unobstructed (DH). For comparison, a group of fetuses without diaphragmatic hernia were subjected to prolonged tracheal ligation (TL; 4-week tracheal ligation, n = 3). Unoperated littermates (n = 8) were used as controls (CTR). All were killed near term. Lung tissue was processed for light and electron microscopy (computerized stereologic morphometry). Type II pneumocytes were identified with antisurfactant protein B antibody.
Four animals in DH + TO and four in DH survived to term. Lung fluid volume (LFV) at 108 days was 5.2 +/- 4.4 mL in DH and 24.6 +/- 6.8 mL in controls (P < .05, Student t test). In DH + TO, LFV increased ninefold (to 48.3 +/- 13.3 mL) by 1 week postocclusion, suggesting accelerated lung growth. At term, lung weight to body weight ratio (LW/BW) was higher in TL (9.85% +/- 1.81%) than in CTR (3.55% +/- 0.56%; P < .05, analysis of variance); LW/BW and parenchymal volume tended to be greater in DH + TO than in DH, and air-exchanging parenchymal volume in DH + TO was similar to CTR (v a 50% reduction in DH), indicating some degree of hyperplasia after temporary occlusion. Pneumocyte II numerical density was decreased more than 10-fold in TL (60 +/- 22 v 826 +/- 324 in CTR, P < .001; it was slightly lower in DH + TO than in CTR, but individual type II pneumocyte cell volume was greater in the latter, and they appeared more mature than in DH (increased granulation by light microscopy, fewer glycogen granules, and abundant lamellar bodies by electron microscopy). Surfactant was also seen in the air spaces in DH + TO and CTR; it was absent in unobstructed CDH and in TL.
Temporary tracheal occlusion in utero does not cause the dramatic decrease in type II pneumocytes seen after prolonged occlusion. Although only minimal increase in lung volume is seen in CDH, catch-up parenchymal growth and maturation occur, most notably in the surfactant-producing system.
患有膈疝的婴儿肺部发育不全、不成熟且缺乏表面活性物质。子宫内气管阻塞被提议作为膈疝的产前治疗方法，通过促进肺的代偿性生长来实现，但同时也会因II型肺细胞的丢失而减少表面活性物质的产生。作者研究了临时气管阻塞是否能引起“追赶性”肺生长和成熟，而不会对表面活性物质系统产生长期气管阻塞的负面影响。
在胎龄65至75天的胎羊中制造膈疝。在108天时，用取栓导管阻塞气管（膈疝+气管阻塞组，n = 6）。14天后，将球囊放气。六只先天性膈疝（CDH）胎儿未进行阻塞（膈疝组）。为作比较，一组无膈疝的胎儿接受长期气管结扎（气管结扎组；4周气管结扎，n = 3）。未手术的同窝胎儿（n = 8）用作对照（对照组）。所有动物均在接近足月时处死。对肺组织进行光镜和电镜处理（计算机化体视形态学）。用抗表面活性蛋白B抗体鉴定II型肺细胞。
膈疝+气管阻塞组和膈疝组各有四只动物存活至足月。膈疝组108天时的肺液量（LFV）为5.2±4.4 mL，对照组为24.6±6.8 mL（P <.05，Student t检验）。在膈疝+气管阻塞组，阻塞后1周时肺液量增加了9倍（至48.3±13.3 mL），提示肺生长加速。足月时，气管结扎组的肺重与体重比（LW/BW）高于对照组（9.85%±1.81%对3.55%±0.56%；P <.05，方差分析）；膈疝+气管阻塞组的LW/BW和实质体积倾向于大于膈疝组，膈疝+气管阻塞组的气体交换实质体积与对照组相似（膈疝组减少50%），表明临时阻塞后有一定程度的增生。气管结扎组的II型肺细胞数量密度降低超过10倍（60±22对对照组的826±324，P <.001；膈疝+气管阻塞组略低于对照组，但后者单个II型肺细胞的细胞体积更大，且看起来比膈疝组更成熟（光镜下颗粒增多，糖原颗粒减少，电镜下板层小体丰富）。在膈疝+气管阻塞组和对照组的气腔中也可见表面活性物质；未阻塞的CDH组和气管结扎组中则没有。
子宫内临时气管阻塞不会像长期阻塞后那样导致II型肺细胞显著减少。虽然CDH中肺体积仅略有增加，但会出现追赶性实质生长和成熟，最明显的是在产生表面活性物质的系统中。
