Submitted on March 15, 2006
Accepted on September 29, 2006
Increased lung expansion alters lung growth but not alveolar epithelial cell differentiation in newborn lambs
Sharon J. Flecknoe1*, Kelly J Crossley1, Giovanna M Zuccala1, Janine E Searle1, Beth J Allison1, Megan J Wallace2, and Stuart Brian Hooper3
1 Physiology, Monash University, Melbourne, Victoria, Australia
2 Department of Physiology, Monash University, Monash University, Australia
3 Physiology, Monash University, Monash University, Victoria, Australia
* To whom correspondence should be addressed. E-mail: sharon.flecknoe{at}med.monash.edu.au.
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 hypothesised 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 cmH2O PEEP (controls, n=5) or 10 cmH2O PEEP (n=5) for 48 hrs beginning at 15±1 days after normal term birth. A further group of non-ventilated 2 week old lambs were used for comparison. We determined wet and dry lung weights, DNA and protein content, a labelling index for proliferating cells, surfactant protein mRNA expression and proportions of AECs using electron microscopy. Although ventilating lambs for 48hrs with 10 cmH2O PEEP did not affect total lung DNA or protein, it significantly increased the proportion of proliferating cells in the lung when compared to non-ventilated 2 week old controls and lambs ventilated with 0 cmH2O 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 week old lambs, but do not alter the proportions of AECs
