To explain certain manifestations of pulmonary disease during childhood, we plan to examine biochemical, morphometric and mechanical properties of lung parenchyma at 5 stages of growth in the pig. We will use theory and methods of solid mechanics to determine the elastic moduli of lung parenchyma and will relate these to elastin and collagen constituents and to parenchymal membrane thickness and surface area per unit volume. Lungs will be examined shortly after birth and at 4 subsequent postnatal stages which have been designed to characterize results of alveolar replication, deposition of elastin, deposition of collagen and alveolar-expansion. Both electron and light microscopy will be used for precise measurement of parenchymal dimensions and for measurements of elastic fiber density per unit surface area. Elastic moduli will be determined at 6 degrees of lung inflation by combining pressure-volume relationships with results of a cylindrical punch method for uniaxial loading. In addition, we will alter the interregional distribution of parenchymal growth in a predictable way by producing unilateral diaphragmatic paralysis during the period of rapid alveolar replication in a separate group of animals. In this group and in a group of sham operated controls, ipsilateral/contralateral pulmonary distending pressure will be measured by bilateral pleural balloons. By comparison of biochemical, morphometric and mechanical results with those in the undisturbed animal, we will test our hypothesis that regional properties of lung parenchyma are determined by regional distending pressure during postnatal growth. Changes in stress-strain characteristics of lungs caused by growth related changes in connective tissue constituents and parenchymal microstructure relate to mechanical interdependence of airspaces. These studies are needed for understanding of congenital lobar emphysema, regional overexpansion of airspaces during mechanical ventilation in infancy and mechanisms of postnatal lung growth.
