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:
  • 项目状态:
    未结题

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

期刊论文数量(0)
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科研奖励数量(0)
会议论文数量(0)
专利数量(0)

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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

OXIDANTS AND ENDOTOXIN INDUCED ENDOTHELIAL INJURY
氧化剂和内毒素引起的内皮损伤
  • 批准号:
    6030723
  • 财政年份:
    1997
  • 资助金额:
    --
  • 项目类别:
OXIDANTS AND ENDOTOXIN INDUCED ENDOTHELIAL INJURY
氧化剂和内毒素引起的内皮损伤
  • 批准号:
    2735296
  • 财政年份:
    1997
  • 资助金额:
    --
  • 项目类别:
OXIDANTS AND ENDOTOXIN INDUCED ENDOTHELIAL INJURY
氧化剂和内毒素引起的内皮损伤
  • 批准号:
    2409244
  • 财政年份:
    1997
  • 资助金额:
    --
  • 项目类别:
CORE--PATHOLOGY
核心--病理学
  • 批准号:
    6109486
  • 财政年份:
    1997
  • 资助金额:
    --
  • 项目类别:
OXIDANTS AND ENDOTOXIN INDUCED ENDOTHELIAL INJURY
氧化剂和内毒素引起的内皮损伤
  • 批准号:
    6184078
  • 财政年份:
    1997
  • 资助金额:
    --
  • 项目类别:
CORE--PATHOLOGY
核心--病理学
  • 批准号:
    6241609
  • 财政年份:
    1996
  • 资助金额:
    --
  • 项目类别:
PATHOGENESIS OF CHRONIC PULMONARY HYPERTENSION
慢性肺动脉高压的发病机制
  • 批准号:
    2224606
  • 财政年份:
    1993
  • 资助金额:
    --
  • 项目类别:
EFFECTS OF HYPOXIA ON THE CORONARY MICROCIRCULATION
缺氧对冠状动脉微循环的影响
  • 批准号:
    6389256
  • 财政年份:
    1993
  • 资助金额:
    --
  • 项目类别:
PATHOGENESIS OF CHRONIC PULMONARY HYPERTENSION
慢性肺动脉高压的发病机制
  • 批准号:
    6183641
  • 财政年份:
    1993
  • 资助金额:
    --
  • 项目类别:
PATHOGENESIS OF CHRONIC PULMONARY HYPERTENSION
慢性肺动脉高压的发病机制
  • 批准号:
    3367639
  • 财政年份:
    1993
  • 资助金额:
    --
  • 项目类别:

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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)
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