Submitted on June 1, 2007
Accepted on January 2, 2008
Postnatal lung function in the developing rat
Ines Bolle1, Gunther Eder2, Shinji Takenaka3, Koustav Ganguly3, Stefan Karrasch3, Claudia Zeller3, Maria Neuner3, Wolfgang G. Kreyling4, Akira Tsuda5, and Holger Schulz, M.D.3*
1 Institute of Inhalation Biology, GSF- National Research Center for Environment and Health, Neuherberg, Bavaria, Germany
2 Neuherberg, Bavaria, Germany; Institute of Inhalation Bilogy, GSF- National Research Center for Environment and Health, Neuherberg, Bavaria, Germany
3 Institute of Inhalation Bilogy, GSF- National Research Center for Environment and Health, Neuherberg, Bavaria, Germany
4 Institute for Inhalation Biology, GSF - Nat. Research Center for Environment & Health, Neuherberg/Muenchen, Germany
5 Physiology Program-Department of Environmental Health, Harvard School of Public Health, Boston, Massachusetts, United States
* To whom correspondence should be addressed. E-mail: schulz{at}gsf.de.
Little is known about lung function during early stages of postnatal maturation although the complex structural changes associated with developing rat lung are well studied. We therefore analyzed corresponding functional (lung volume, respiratory mechanics, intrapulmonary gas mixing and gas exchange) and structural changes (alveolar surface area, mean linear intercept length and alveolar septal thickness) of the developing rat lung between 7-90 days. Total lung capacity (TLC) increased from 1.54 ± 0.07 ml to 16.7 ± 2.46 ml (mean ± SD) in proportion to body weight, but an increase in body weight exceeded that in lung volume by almost 2 fold. Series dead space increased from 0.21 ± 0.03 ml to 1.38 ± 0.08 ml, but decreased relative to TLC from 14% to 8%, indicating parenchymal growth exceeded that of conducting airways. Diffusing capacity (DCO) increased from 8.1 ± 0.8 µmol/min/hPa to 214.1 ± 23.5 µmol/min/hPa, corresponding to a substantial increase in surface area from 744 ± 20 cm2 to 6536 ± 488 cm2. DCO per unit of lung volume is considerably lower in the immature lung, as DCO/TLC in 7 day-old rats was only 42% of that of adult (90 day-old) rats. This is in contrast to humans where infants and adults show comparable specific diffusing capacity. Our functional and structural analysis shows that gas exchange is limited in the immature rat lung. The pivotal step for improving gas exchange occurs with the transition from bulk alveolarization into the phase of expansion of airspaces with septal reconstruction and micro-vascular maturation.
