Rescue of the Hypoplastic Lung by Prenatal Cyclical Strain

Abstract

We determined the effects of sustained and cyclical prenatal mechanical strain on the hypoplastic lung of the ovine model of congenital diaphragmatic hernia. Over a period of 4 weeks in late gestation, repeated cyclical tracheal occlusion for 23 hours with 1-hour release stimulated minimal growth, but promoted maturation with the development of a saccular lung. In contrast, a cycle consisting of 47 hours with 1-hour release induced optimal lung growth and morphologic maturation of the hypoplastic lung parenchyma. Sustained occlusion resulted in exaggerated lung growth, exceeding that of unaffected controls, and abnormal alveolar development. The extent of induction of lung growth by mechanical strain was inversely proportional to the number of alveolar type II cells remaining in the lung epithelium. These studies show that, although mechanical strain is capable of inducing lung growth and differentiation, cyclical strain is a prerequisite for normal development and that mechanically induced growth occurs at the expense of the alveolar type II cell. We conclude that cyclical strain may allow optimal alveolar development while maintaining a population of alveolar type II cells and may thus facilitate an improvement in postnatal lung function in infants with congenital diaphragmatic hernia.

Predictors of neonatal morbidity in fetuses with severe isolated congenital diaphragmatic hernia undergoing fetoscopic tracheal occlusion

“…However, even after correction for gestational age at birth, early prenatal balloon removal improved the chances of survival. In animal experiments, cyclical or temporary occlusion has been shown to improve lung maturation 26,27,31 . This might also be the case clinically, although early morbidity parameters were unaffected by prenatal balloon removal.…”

“…The FETO procedure has been described in detail 22,23,28 . Briefly it consists of the percutaneous fetoscopic insertion of a balloon into the fetal trachea, which in general is performed at approximately 26-28 (range, [23][24][25][26][27][28][29][30][31][32][33] weeks' gestation. The balloon is preferentially removed in utero at approximately 34 weeks by tracheoscopy or ultrasound-guided puncture.…”

Prenatal diagnosis, prediction of outcome and in utero therapy of isolated congenital diaphragmatic hernia

“…Fetal breathing movements allow the fluid to exit the airways, leveling that pressure. This results in periods of tissue stretch, its cyclical nature being important for an appropriate balance between growth and differentiation (Nelson et al, 2005). Surgical tracheal occlusion (TO) takes advantage of this principle, its effects being a function of the timing and duration.…”

“…Nelson later demonstrated that best results were obtained with a protocol of 47 h of occlusion alternated with 1 h of release. He did this between 110 (cannalicular phase) and 138 days of ovine gestation (saccular; term = 145 days; Figure 4) (Nelson et al, 2005).…”

Cirurgia fetal no contexto atual

“…Com a realização dos experimentos em animais e humanos, começou-se a observar que, apesar de a oclusão endotraqueal fetal promover aumento na massa pulmonar e melhorar as trocas gasosas, ela também impedia o desenvolvimento e maturação dos pneumócitos do tipo II nos alvéolos, bem como a produção de surfactante alveolar 45 . Assim, começou a se propor que a oclusão traqueal fetal fosse revertida ainda no período intrauterino 46 .…”