FETAL LUNG GROWTH AFTER TRACHEAL LIGATION IS NOT SOLELY A PRESSURE PHENOMENON

Fetal tracheal ligation increases lung growth in utero, making it pote ntially applicable for antenatal treatment of diaphragmatic hernia. Th is phenomenon has been ascribed to increased intratracheal pressure, w hich activates as yet unidentified pulmonary stretch receptors. The pu rpose of this study was to determine whether the composition of lung f luid has any effect on fetal lung development after tracheal obstructi on. Six sets of fetal lamb twins underwent tracheal ligation with plac ement of intratracheal catheters at 122 days' gestation (term, 145 day s). In group 1 (n = 6), tracheal fluid was aspirated daily, measured, and replaced with equal volumes of saline. Their respective twins (gro up 2, n = 6) had daily reinfusion of their own tracheal aspirates. Int ratracheal pressure was recorded daily in both groups. Unobstructed fe tal lambs (n = 7) were used as negative controls. Animals were killed on postoperative day 14 (136 days). Lungs were weighed, perfusion fixe d at 25 cm H2O, and processed for standard morphometric analysis. Intr atracheal pressure remained between 3 and 5 torr in both experimental groups throughout the entire postoperative period. In all 12 experimen tal fetuses, tracheal ligation resulted in an almost threefold increas e in lung fluid volume by day 1; a slight decrease at a mean of 2.4 da ys; and a second surge from day 4 on. Lung fluid volume was significan tly higher in group 2 than in group 1 at all measured time points (P < .05, Wilcoxon rank sum test) except on days 3, 4, and 8 (P =.06). Lung weight per body weight (LW/BW) at delivery was 0.045 +/- 0.008 in gro up 1, not significantly different from unobstructed controls (0.038 +/ - 0.006). LW/BW in group 2 was 0.055 +/- 0.010, significantly larger t han either group 1 or control (P <.05, single factor analysis of varia nce). Air space fraction was comparable between the three groups. Alve olar numerical density was significantly lower in groups 1 and 2 than in unobstructed controls (P <0.05). Replacement of tracheal fluid with saline inhibits the lung hypertrophy seen after tracheal ligation. Th is phenomenon therefore appears more dependent on tracheal fluid growt h factors than on increased intratracheal pressure after obstruction. The immediate decrease in net lung fluid production after saline excha nge suggests that these humoral factors play an important role in the initiation of lung cell proliferation. Copyright (C) 1997 by W.B. Saun ders Company.