We have recently found strong evidence in dogs and sloths that the intrathoracic position of the heart is a major determinant of regional lung air content, while other studies have demonstrated that vascular geometry (vascular conductance) plays an important role in distribution of regional pulmonary blood flow. It appears that distribution of regional pulmonary blood flow and regional lung air content may be governed by overlapping (gravitational factors.), but not identical mechanisms. The matching of regional air content and pulmonary flow (V/Q) in the lungs is necessary for efficient gas exchange and yet if determinants of both components are not identical, it is possible for mismatches to develop. We propose to utilize high-speed x-ray volumetric computed tomography (the Dynamic Spatial Reconstructor and Imatron's C- 1000 scanner) to evaluate the relative role of body orientation (gravity), chest wall shape (rib cage and diaphragm), intrathoracic location of the heart, and pulmonary vascular geometry in determinining regional distribution of lung air content and pulmonary blood flow in anesthetized Beagle dogs. Three major hypotheses will be tested: 1) The intrathoracic position of the heart is a major determinant of regional lung air content, 2) The rib cage and diaphragm control the shape of the lung and hence, may alter regional lung air content, but the role of the rib cage and diaphragm shape is minimized by lobar slippage, and 3) Regional vascular geometry has an important influence on the distribution of regional perfusion. Because of the differences in pulmonary arterial tree branching structure of dogs vs. African miniature goats, we will study 6 african miniature goats in year 3 to evaluate differences or similarities in V/Q distribution patterns as compared to dogs as one test of hypothesis 3. Because of the unique data sets which will be obtained, whereby we will have detailed mapping of regional lung expansion and respiratory system geometry, we will also perform simultaneous helium bolus and nitrogen single breath washout tests. These tests are widely utilized in both research and clinical medicine as an index of intra- and inter- regional differences of ventilation, and yet the associated physiology remains unclear. As an important first step to our studies, we will calibrate regional pulmonary blood flow measurements obtained via DSR and Imatron scanning by comparison with distribution of color coded microspheres. Recent data in heart and kidney show peak regional brightness following a bolus contrast injection to be an accurate index of regional blood flow.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL042672-02
Application #
3361009
Study Section
Diagnostic Radiology Study Section (RNM)
Project Start
1988-09-30
Project End
1993-09-29
Budget Start
1989-09-30
Budget End
1990-09-29
Support Year
2
Fiscal Year
1989
Total Cost
Indirect Cost
Name
University of Pennsylvania
Department
Type
Schools of Medicine
DUNS #
042250712
City
Philadelphia
State
PA
Country
United States
Zip Code
19104
Zaman, Aisha; Cui, Zheng; Foley, Joseph P et al. (2005) Expression and role of the hyaluronan receptor RHAMM in inflammation after bleomycin injury. Am J Respir Cell Mol Biol 33:447-54
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Hoffman, E A; Tajik, J K; Kugelmass, S D (1995) Matching pulmonary structure and perfusion via combined dynamic multislice CT and thin-slice high-resolution CT. Comput Med Imaging Graph 19:101-12
Olson, L E; Hoffman, E A (1994) Lung volumes and distribution of regional air content determined by cine X-ray CT of pneumonectomized rabbits. J Appl Physiol 76:1774-85
Hoffman, E A; Hoford, J D (1993) Tool box-based cardiac volumes: visualization and quantitation by computed tomography. Am J Card Imaging 7:164-78

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