The essence of the mechanical behavior of the mammalian lung is its expansibility and its state of passive tension. Many aspects of lung function depend critically on this state of tension and its dysfunction is at the core of the pathophysiology of emphysema, pulmonary fibrosis, adult respiratory distress syndrome, and other disorders. The structural basis for the lung's recoil properties, however, is not well understood. Our approach is to examine the structure of the alveolar parenchyma, characterizing the topology, configuration, and composition of the alveolar septa and their borders and analyzing its mechanical behavior as a tensed """"""""cable- membrane"""""""" structure. The """"""""cables"""""""" are elastin-rich connective tissue structures, located in the free septal borders and two-way septal junctions (never at the most frequent three-way septal junction) and forming a network within each ductal unit. The """"""""membranes"""""""" are the alveolar septa, bearing tensions in their air- liquid interfaces and fine connective tissue framework in parallel and constituting a honeycomb-like network. The two networks are geometrically and compositionally distinct. The tensions which they bear and the configuration of the parenchymal airspaces reflect an intimate series mechanical interaction. We propose to characterize the detailed anatomy and three- dimensional configuration of the tension-bearing structures of the lung and to draw inferences regarding their mechanics. Lungs will be prepared by intravascular perfusion fixation/dehydration to preserve configuration under specific experimental conditions. Standard stereological techniques and a confocal laser scanning microscope (for obtaining precise, digital images and three- dimensional anatomic data from a relatively thick specimen) will be used to obtain lengths, curvatures, angles of meeting, and topology of the septa and their borders. We will analyze these data as an assembly of tensed cables and membranes, drawing inferences about the isotropy of tensions in the septum, the local constancy of tensions among adjoining septa, the constancy of tensions along and among the cables, the role of the interlobular septa, the topologies of the alveolar septum, the alveolus, and the ductal unit. These relationships will be examined with regard to location in the ductal unit and with experimental variables of lung distension, surface tension, species, and progressive damage after elastase instillation.
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