and Specific Aims.) The long term goal of this project is to determine the mechanisms by which the bronchial circulation attenuates the increased pulmonary vascular permeability cause by ischemia-reperfusion (IR) injury in isolated sheep lungs. Based on preliminary data, it is hypothesized that the protective effect results from perfusion of the pulmonary vascular vasa vasorum by the bronchial circulation. Perfusion of pulmonary vasa vasorum could protect by delivering metabolic substrates and antioxidants, removing toxic metabolites or stimulating the release of protective factors within pulmonary vessels.One such protective factor may be nitric oxide (NO).
Specific Aim 1 proposes to characterize the morphology and hemodynamics of pulmonary vasa vasorum. To confirm that bronchial arterial (BA) blood flow prevents changes in pulmonary vascular permeability via vasa vasorum perfusion, it will be determine if the increased permeability caused by IR injury and the protection conferred by BA perfusion occur in extraalveolar vessels supplied by vasa vasorum.
Specific Aim 2 proposes to determine if a protective effect of BA perfusion during pulmonary ischemia without reperfusion is mediated by vasa vasorum perfusion or bronchopulmonary anastomotic flow.
Specific Aim 3 will determine if the protective effect of vasa vasorum perfusion is dependent on perfusate characteristics, such as contents of oxygen, glucose, albumin, and erythrocytes or perfusate flow. To determine if vasa vasorum flow protects via generation of NO, inhibitors of NO synthesis and NO donor compounds will be used to block and mimic, respectively, the protective effect of vasa vasorum perfusion. The separate effects of IR injury on bronchial and pulmonary vessels will be examined by comparing measurements of vascular permeability and NO production in both circulations after variable lengths of ischemia and reperfusion. These results may provide new information about the physiology and function of pulmonary vasa vasorum and could have implications with respect to clinical conditions where vasa vasorum flow is reduced, such as lung transplantation.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
First Independent Research Support & Transition (FIRST) Awards (R29)
Project #
1R29HL050504-01
Application #
3474199
Study Section
Lung Biology and Pathology Study Section (LBPA)
Project Start
1993-08-15
Project End
1998-07-31
Budget Start
1993-08-15
Budget End
1994-07-31
Support Year
1
Fiscal Year
1993
Total Cost
Indirect Cost
Name
Johns Hopkins University
Department
Type
Schools of Medicine
DUNS #
045911138
City
Baltimore
State
MD
Country
United States
Zip Code
21218
Pearse, D B; Becker, P M; Permutt, S (2001) Effect of changing vascular volume on measurement of protein reflection coefficient in ischemic lungs. Am J Physiol Heart Circ Physiol 280:H918-24
Pearse, D B; Becker, P M (2000) Effect of time and vascular pressure on permeability and cyclic nucleotides in ischemic lungs. Am J Physiol Heart Circ Physiol 279:H2077-84
Dodd-O, J M; Pearse, D B (2000) Effect of the NADPH oxidase inhibitor apocynin on ischemia-reperfusion lung injury. Am J Physiol Heart Circ Physiol 279:H303-12
Pearse, D B; Dodd, J M (1999) Ischemia-reperfusion lung injury is prevented by apocynin, a novel inhibitor of leukocyte NADPH oxidase. Chest 116:55S-56S
Pearse, D B; Wagner, E M; Permutt, S (1999) Effect of ventilation on vascular permeability and cyclic nucleotide concentrations in ischemic sheep lungs. J Appl Physiol 86:123-32
Pearse, D B; Dahms, T E; Wagner, E M (1998) Microsphere-induced bronchial artery vasodilation: role of adenosine, prostacyclin, and nitric oxide. Am J Physiol 274:H760-8
Pearse, D B; Fessler, H E; Wagner, E M (1995) Polystyrene microspheres decrease bronchial artery resistance in anesthetized sheep. Am J Physiol 269:H1037-43