As a result of congestive heart failure or mitral stenosis, venous pressure in the pulmonary circulation is chronically elevated. Despite the venous hypertension, alveolar flooding and respiratory distress do not always occur. The hypotheses of this proposal are that structural and functional adaptations to chronic pulmonary venous hypertension limit or prevent alveolar edema formation and that some or all of these adaptations are dependent upon the duration of that hypertensive state. We will focus upon adaptations within the pulmonary microcirculation, lung interstitium, and the alveolo-capillary barrier, since all of these sites are known to play a role in the overall exchange of fluid and solutes in the lung.
Specific Aims are to determine whether 1) regulation of pulmonary capillary pressure is hampered in heart failure and related to structural changes in the extra-alveolar microvasculature; 2) the pulmonary capillary barrier becomes less permeable to water and macromolecules and more resistant to high vascular pressure and chemical injury, and if these changes are related to progressive structural remodeling of the alveolocapillary barrier; 3) changes in the composition of the lung interstitial matrix contribute to a larger margin of safety against pulmonary edema formation in heart failure; and 4) the absorption of alveolar fluid is enhanced under these hypertensive conditions. Rapid ventricular pacing from 1 to 4 months will be used to induce heart failure and chronic pulmonary venous hypertension in the dog, allowing us to evaluate the temporal progression of pulmonary adaptations.
These aims will be pursued using measures of pulmonary hemodynamics and vascular structure, permeability, exchange of fluid and solutes, and interstitial matrix. Both the in situ lung lymphatic preparation and lung lobes isolated and perfused ex vivo with autologous blood will be used.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL039045-12
Application #
2735131
Study Section
Lung Biology and Pathology Study Section (LBPA)
Project Start
1988-03-01
Project End
2000-06-30
Budget Start
1998-07-01
Budget End
1999-06-30
Support Year
12
Fiscal Year
1998
Total Cost
Indirect Cost
Name
University of South Alabama
Department
Physiology
Type
Schools of Medicine
DUNS #
City
Mobile
State
AL
Country
United States
Zip Code
36688