Increased lung expansion alters lung growth but not alveolar epithelial cell differentiation in newborn lambs

Abstract

Although increased lung expansion markedly alters lung growth and epithelial cell differentiation during fetal life, the effect of increasing lung expansion after birth is unknown. We hypothesized that increased basal lung expansion, caused by ventilating newborn lambs with a positive end-expiratory pressure (PEEP), would stimulate lung growth and alter alveolar epithelial cell (AEC) proportions and decrease surfactant protein mRNA levels. Two groups of lambs were sedated and ventilated with either 0 cmH(2)O PEEP (controls, n = 5) or 10 cmH(2)O PEEP (n = 5) for 48 h beginning at 15 +/- 1 days after normal term birth. A further group of nonventilated 2-wk-old lambs was used for comparison. We determined wet and dry lung weights, DNA and protein content, a labeling index for proliferating cells, surfactant protein mRNA expression, and proportions of AECs using electron microscopy. Although ventilating lambs for 48 h with 10 cmH(2)O PEEP did not affect total lung DNA or protein, it significantly increased the proportion of proliferating cells in the lung when compared with nonventilated 2-wk-old controls and lambs ventilated with 0 cmH(2)O PEEP (control: 2.6 +/- 0.5%; 0 PEEP: 1.9 +/- 0.3%; 10 PEEP: 3.5 +/- 0.3%). In contrast, no differences were observed in AEC proportions or surfactant protein mRNA levels between either of the ventilated groups. This study demonstrates that increases in end-expiratory lung volumes, induced by the application of PEEP, lead to increased lung growth in mechanically ventilated 2-wk-old lambs but do not alter the proportions of AECs.

The Effect of Extended Continuous Positive Airway Pressure on Changes in Lung Volumes in Stable Premature Infants: A Randomized Controlled Trial

“…Congenital diaphragmatic hernia prevents in utero lung expansion and results in hypoplastic lungs, 25,26 and complete congenital airway obstruction prevents lung fluid from leaving the trachea and produces a large, hyperplastic lung. 27 Animal models of in utero congenital diaphragmatic hernia have shown that fetal trachea occlusion increases the lungs' distending pressure and results in increased fetal lung growth, 28,29 capillary growth, and epithelial branching. [30][31][32][33] The mechanical strain from CPAP applied to the lungs of young animals can stimulate lung growth and have other beneficial molecular effects.…”

Computer Tomographic Illustration of the Development of the Pulmonary Function in Bovine Neonates until the Twenty-First Day Postnatum

“…De Zabala and Weinmann [27] had indicated earlier that the alveolar maturation lasted beyond the fetal period and might extend up into the early postuterine period. Evidence for this assumption could be found in the experimental studies on fetal sheep and lambs by Flecknoe et al [16, 55]. These authors showed that in the last trimester of gestation of sheep fetuses, the sum of the alveolar endothelial cells (AEC) of type II increases disproportionately.…”

Potential Contribution of Type I Alveolar Epithelial Cells to Chronic Neonatal Lung Disease

“…This is illustrated by the studies of continuous static expansion in sheep. When done in the fetus, the proportion of AEC1 cells went up markedly (27), but this was not seen with high versus low PEEP ventilation in 2-week-old lambs (38). …”