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.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Method to Extend Research in Time (MERIT) Award (R37)
Project #
5R37HL026863-13
Application #
2216026
Study Section
Special Emphasis Panel (NSS)
Project Start
1980-07-01
Project End
1997-03-31
Budget Start
1994-09-15
Budget End
1995-03-31
Support Year
13
Fiscal Year
1994
Total Cost
Indirect Cost
Name
Memorial Hospital of Rhode Island
Department
Type
DUNS #
City
Pawtucket
State
RI
Country
United States
Zip Code
02860
Oldmixon, E H; Carlsson, K; Kuhn 3rd, C et al. (2001) alpha-Actin: disposition, quantities, and estimated effects on lung recoil and compliance. J Appl Physiol 91:459-73
Charles, A; Dawicki, D D; Oldmixon, E et al. (1997) Studies on the mechanism of short-term regulation of pulmonary artery endothelial cell Na/K pump activity. J Lab Clin Med 130:157-68
Butler, J P; Oldmixon, E H; Hoppin Jr, F G (1996) Dihedral angles of septal ""bend"" structures in lung parenchyma. J Appl Physiol 81:1800-6
Hoppin Jr, F G (1995) Parenchymal mechanics and asthma. Chest 107:140S-144S
Oldmixon, E H; Butler, J P; Hoppin, F G (1994) Semi-automated measurement of true chord length distributions and moments by video microscopy and image analysis. J Microsc 175:60-9
Oldmixon, E H; Carlsson, K (1993) Methods for large data volumes from confocal scanning laser microscopy of lung. J Microsc 170:221-8
Oldmixon, E H; Hoppin Jr, F G (1991) Alveolar septal folding and lung inflation history. J Appl Physiol 71:2369-79
Oldmixon, E H; Hoppin Jr, F G (1989) Distribution of elastin and collagen in canine lung alveolar parenchyma. J Appl Physiol 67:1941-9
Oldmixon, E H; Butler, J P; Hoppin Jr, F G (1989) Lengths and topology of alveolar septal borders. J Appl Physiol 67:1930-40
Oldmixon, E H (1988) Mallory's phloxine B-methylene blue-azure II stain emphasizes elastin and collagen bundles in epoxy embedded lung. Stain Technol 63:165-70

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