The overall goal of this proposal is to determine the role of the bronchial circulation in the uptake of soluble, hydrophilic particles from the surface of conducting airways. The bronchial artery perfuses the airways from the level of the carina to respiratory bronchioles. Uptake into the mucosal capillaries of the bronchial vasculature provides systemic access of all soluble particles that are deposited on the airway surface and traverse the epithelium. Thus, both therapeutically and toxicologically active particles can be taken up by the bronchial vasculature. Using inert, radiolabeled, hydrophilic particles (technetium-99m-labeled diethylenetriamine pentaacetic acid) and gamma camera counting and imaging, the time course of soluble particle clearance from the airway surface and uptake by the bronchial microvasculature will be determined in sheep in which the bronchial artery is cannulated and bronchial blood flow controlled. How changes in blood flow affect the uptake of labeled particles deposited specifically in the conducting airways will be determined. Furthermore, the importance of bronchial perfusion on particle uptake after eliciting changes in the airway wall that are a consequence of bronchial vascular pathology will be studied. These include airway wall edema, induced by the infusion of bradykinin directly into the bronchial artery and bronchial vascular engorgement resulting from left atrial hypertension. Using fluorescent microspheres infused directly into the bronchial artery, we will determine whether changes in perfusion distribution account for the mechanism by which alterations in uptake occur. These studies will provide new information regarding the extent of soluble particle uptake by the systemic circulation of the conducting airways. Furthermore, the results will contribute to an understanding of the factors that both limit and enhance uptake and distribution of aerosols.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL058577-04
Application #
6389695
Study Section
Respiratory and Applied Physiology Study Section (RAP)
Program Officer
Mastin, Patrick
Project Start
1998-07-17
Project End
2002-06-30
Budget Start
2001-07-01
Budget End
2002-06-30
Support Year
4
Fiscal Year
2001
Total Cost
$202,189
Indirect Cost
Name
Johns Hopkins University
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
001910777
City
Baltimore
State
MD
Country
United States
Zip Code
21218
Wagner, Elizabeth M; Brown, Robert H (2002) Blood flow distribution within the airway wall. J Appl Physiol 92:1964-9
Foster, W M; Wagner, E M (2001) Bronchial edema alters (99m)Tc-DTPA clearance from the airway surface in sheep. J Appl Physiol 91:2567-73
Wagner, E M; Foster, W M (2001) Interdependence of bronchial circulation and clearance of 99mTc-DTPA from the airway surface. J Appl Physiol 90:1275-81