The inhalation of smoke produces severe pulmonary problems which greatly increase the morbidity and mortality in patients with a cutaneous burn injury. This proposal will demonstrate in the chronic sheep model that smoke inhalation causes hyperemia and microvascular permeability changes in the upper respiratory tract producing an exudate rich in inflammatory mediators. These mediators include thromboxane A2, histamine, leukotrienes and free oxygen radicals. In combination with cells shed from within the airways this exudate forms casts in the tracheobronchial tree causing severe airway obstruction. Plasma proteins and inflammatory mediators released in the upper airways stimulate macrophages to produce and release chemotactic substances causing polymorphonuclear leukocytes to marginate and release proteolytic enzymes and free 02 radicals in the interstitium with a concomitant direct destruction of ciliated epithelial and mucous producing cells. Samples of plasma and lymph will be collected from isolated trachea and from bilateral and unilateral lung models before and following smoke inhalation injury. These will be analyzed for inflammatory mediators released at the injury site. Topical and systemic modulation of tracheobronchial inflammatory mediators may alter the progressive pulmonary dysfunction and high mortality characteristic of severe smoke inhalation injury.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
1R01HL037411-01A1
Application #
3353042
Study Section
Surgery and Bioengineering Study Section (SB)
Project Start
1987-08-01
Project End
1990-07-31
Budget Start
1987-08-01
Budget End
1988-07-31
Support Year
1
Fiscal Year
1987
Total Cost
Indirect Cost
Name
University of Texas Medical Br Galveston
Department
Type
Schools of Medicine
DUNS #
041367053
City
Galveston
State
TX
Country
United States
Zip Code
77555
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Dong, Y L; Fleming, R Y; Yan, T Z et al. (1993) Effect of ibuprofen on the inflammatory response to surgical wounds. J Trauma 35:340-3
Ashley, K D; Herndon, D N; Traber, L D et al. (1992) Systemic blood flow to sheep lung: comparison of flow probes and microspheres. J Appl Physiol 73:1996-2003
Waymack, J P; Herndon, D N (1992) Nutritional support of the burned patient. World J Surg 16:80-6
Traber, D L; Lentz, C W; Traber, L D et al. (1992) Lymph and blood flow responses in central airways. Am Rev Respir Dis 146:S15-8

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