INFLAMMATION OF THE LUNG AND CHRONIC PULMONARY HYPERTENSION
肺部炎症和慢性肺动脉高压
基本信息
- 批准号:3858696
- 负责人:
- 金额:--
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:
- 资助国家:美国
- 起止时间:至
- 项目状态:未结题
- 来源:
- 关键词:acetylcysteine air embolism allopurinol antioxidants disease /disorder model eicosanoid metabolism endotoxins free radicals indomethacin inflammation leukocyte depletion therapy lipid peroxides lipoxygenase neutrophil platelet activating factor prostaglandin inhibitors pulmonary circulation pulmonary circulation obstruction pulmonary edema pulmonary hypertension radiobiology radioimmunoassay respiratory function sheep transforming growth factors vascular endothelium vasoconstriction
项目摘要
In this project, we will examine the hypothesis that persistent
pulmonary hypertension develops in association with
inflammation of the lungs. This development is due to
generation and release of toxic oxygen metabolites by activated
neutrophils sequestered in the lungs resulting in release of
vasoconstrictor lipid mediators (eicosanoids or platelet
activating factor). We will combine physiological ,
morphological and biochemical techniques to characterize
responses of the pulmonary circulation to thoracic irradiation,
chronic air embolization and repeated intravenous infusions of
endotoxin. Physiologic measurements will include pulmonary
hemodynamics and gas exchange as well as assessment of the
response of the pulmonary circulation to hyperoxia, hypoxia and
the potent vasoconstrictor, PGH2-A (the 9-methylene cyclic
ether analog of PGH2). Morphological studies will be conducted
on lung biopsy tissue taken at baseline and at weekly or two
weekly periods following the beginning of each intervention; in
addition, the heart and lungs will be studied postmortem.
Biochemical measurements will include lung tissue
concentrations of antioxidant enzymes at baseline and over the
course of the experiment; and measurement of lung lymph and
blood plasma concentrations of eicosanoid metabolites, platelet
activating factor and conjugated dienes. The oxygen metabolite
hypothesis will be tested by determining the effects of the free
radical scavenger, N-acetyl cysteine, and the xanthine oxidase
inhibitor, allopurinol, on the responses of the lungs' circulation to
chronic inflammation. Animals will also be studied following
granulocyte depletion to determine whether neutrophils are
essential to the pulmonary hypertensive response and to
determine whether neutrophils are responsible for generation
lipid mediators in the models to be studied. Effects of 5-
lipoxygenase inhibitors (e.g., L-651, 39.2-00N10) and leukotriene
receptor antagonists (e.g., FLP 55712) will be studied to
determine whether lipoxygenase products participate in the
pathogenesis of the response. These studies will elucidate the
pathophysiology and pathogenesis of chronic pulmonary
hypertension resulting from diffuse lung inflammation and will
provide rationales for pharmacologic interventions which may
prevent or reverse the effects of chronic inflammation on the
lung circulation.
在这个项目中,我们将检验假设的持久性
项目成果
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BARBARA O MEYRICK其他文献
BARBARA O MEYRICK的其他文献
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{{ truncateString('BARBARA O MEYRICK', 18)}}的其他基金
相似海外基金
The study of prevention of venous air embolism -Concerning with dural sinus pressure
预防静脉空气栓塞的研究——与硬脑膜窦压力有关
- 批准号:
62480302 - 财政年份:1987
- 资助金额:
-- - 项目类别:
Grant-in-Aid for General Scientific Research (B)