Ozone and acid fog and acid rain (including sulfuric acid aerosols) are of major public health concern, in part because they are capable of producing measurable transient effects on the lungs of susceptible subjects, at concentrations which can occur in ambient pollutant episodes, and in part because they may act synergistically to produce effects on the lung greater than that produced by individual exposures. Knowledge concerning the possible deleterious effects of ozone-acid synargisms on the respiratory tract is still extremely meager. A sheep model system is proposed to examine the synergistic effect between ozone and respirable-sized sulfuric acid aerosols. In the current study we will use a multidisciplinary approach designed to evaluate the effects of ozone, acid aerosol, and their combination, on respiratory tract epithelial and endothelial permeability. Bronchoalveolar clearance of 99mTc-DTPA radioaersol from the lung will be used to determine epithelial permeability and results obtained will be compared to appearances of protein, lysosomal enzymes and cells in bronchoalveolar lavage carried out via a standard methodology. Sheep lung lymph will obtained to evaluate endothelial permeability and possible clearances of 99mTc-DTPA via lung lymphatics. Finally, in a separate series of sheep exposed to an identical protocol of ozone, acid aerosol or combined ozone-acid aerosol, airway blood flow will be continuously monitored using a Doppler flowmeter-telemetry system. Changes in airway blood flow are expected to provide an index of neurogenic or mediator- related events occurring in airway interstitium and which would be expected to effect airway smooth muscle as well as airway microvasculature. In subsequent years we plan to specifically examine for the role(s) of oxy radical productions (and other potential mediators) on this synergism via uses of various infused and aerosolized quenching agents and radical scavengers as in vivo antagonists.

Agency
National Institute of Health (NIH)
Institute
National Institute of Environmental Health Sciences (NIEHS)
Type
Research Project (R01)
Project #
5R01ES004461-02
Application #
3252628
Study Section
(SRC)
Project Start
1987-09-01
Project End
1990-08-31
Budget Start
1988-09-01
Budget End
1989-08-31
Support Year
2
Fiscal Year
1988
Total Cost
Indirect Cost
Name
University of California Davis
Department
Type
Schools of Veterinary Medicine
DUNS #
094878337
City
Davis
State
CA
Country
United States
Zip Code
95618
Gunther, R A; Yousef, M A; Schelegle, E S et al. (1992) Corticosteroid administration modifies ozone-induced increases in sheep airway blood flow. Am Rev Respir Dis 146:660-4
Lin, V W; Kramer, G C; Parsons, G H et al. (1991) Laser Doppler velocimetry of tracheal blood flow in sheep. Respir Physiol 85:341-54
Schelegle, E S; Gunther, R A; Parsons, G H et al. (1990) Acute ozone exposure increases bronchial blood flow in conscious sheep. Respir Physiol 82:325-35
Cross, C E; Forte, T; Stocker, R et al. (1990) Oxidative stress and abnormal cholesterol metabolism in patients with adult respiratory distress syndrome. J Lab Clin Med 115:396-404
Hornof, W J; Schelegle, E; Kammerman, M et al. (1989) Ozone-induced accelerated lung clearance of 99mTc-DTPA aerosol in conscious sheep. Respir Physiol 77:277-90
Hornof, W J; O'Callaghan, M W; Gunther, R A et al. (1988) Lung clearance of 99mTc-DTPA aerosol in conscious sheep. Respir Physiol 72:375-89