Tracheal side effects of endoscopic balloon tracheal occlusion in the fetal lamb model

Objective: To evaluate effects of in-utero endoluminal balloon tracheal occ lusion (TO) as suggested for the treatment of Congenital Diaphragmatic Hern ia (CDH) on the higher airways of a fetal lamb model. Study design: Fetuses from time-dated pregnant ewes underwent at 94 days (term = 145 days) in-ut ero tracheal occlusion. In study animals an endoluminal, detachable balloon was placed by tracheoscopy. For that purpose a 1.2 mm fibre-optic, semi-ri gid endoscope and a medically graded latex balloon were used. In group I (n = 9) lambs were delivered after 2 weeks. In group II (n = 8) the tracheal occlusion was released after 2 weeks, to allow in-utero recovery until term . In positive control animals (group III; n = 5) the trachea was clipped at 98 days and fetuses were harvested near term by cesarean section. A total of 17 contralateral littermates in multiple pregnancies served as negative controls. After macroscopic inspection of the trachea, sections were evalua ted by light microscopy. Alterations were scored with an empirical interval score for each of the different anatomical elements in the fetal trachea ( epithelium, submucosa, cartilage, pars membranacea). Results: For the anima l experiments in group I, all balloons were found in place and according to the pulmonary response they were obstructive. Tracheas were macroscopicall y dilated by the plug mainly due to elongation of the pars membranacea. The total histologic score was correlated to the increase in circumference (me an increase: 3.0 mm). In nearly all cases, the tracheal epithelium at the l evel of the plug had lost its typical folding pattern. In 44% of cases, loc al epithelial defects were observed and in 33% of cases there was squamous metaplasia. A chronic inflammatory response was present in over half of the cases, sometimes with giant cell reaction. In group II (the in-utero recov ery group) the total score was significantly lower than in group I, with mu ch less prominent unfolding and absence of epithelial defects. Squamous met aplastia was still present in half of the cases; whereas inflammatory respo nses were less frequent. In group III the trachea expanded normally after r emoval of the clip. The epithelium had compacted folds, and cilia were well preserved. In two animals however, intraluminal synechia were observed. Be low the level of occlusion animals of groups I and II all showed areas of u nfolding, but without metaplasia or epithelial defects. Conclusion: Trachea l obstruction by means of endoluminal plugging has been suggested as an alt ernative in-utero treatment for congenital diagphragmatic hernia. The ballo on causes mild epithelial changes, such as unfolding, limited epithelial de fects (<25% of the exposure surface) and local inflammatory changes. These changes disappear nearly completely following in-utero unplugging during th e rest of gestation. Unfolding of the epithelium is also seen in the trache a under the plug. (C) 2000 Elsevier Science Ireland Ltd. All rights reserve d.