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PULMONARY MICROEMBOLI: THE ROLE OF OXYGEN RADICALS

肺微栓塞：氧自由基的作用

基本信息

批准号：
3087164
负责人：
RONALD C ALLISON
金额：
$ 7.56万
依托单位：
UNIVERSITY OF SOUTH ALABAMA
依托单位国家：
美国
项目类别：
财政年份：
1984
资助国家：
美国
起止时间：
1984-07-01 至 1989-06-30
项目状态：
已结题

项目摘要

The Adult Respiratory Distress Syndrome (ARDS) is characterized initially by increased permeability of the pulmonary microvasculature. In ARDS there appears to be a potential involvement of leukocytes, platelets, oxygen radicals, prostaglandins, complement activation, and intravascular coagulation and fibrinolysis. The observation of both platelet-fibrin plugs and leukostatic plugs in the lungs of man and experimental animals has focused attention on microemboli, and has led to their use of experimental models of acute lung injury. Although the role of superoxide and other oxygen radicals has been described in oxygen toxicity, their role in the injury due to pulmonary microemboli has received little attention and is the overall objective of the proposed research. The isolated, perfused dog lung label will be the basic experimental preparation. The advantages of this preparation are 1) it is perfused with whole blood with all of its constituents, 2) the weight of the lobe is continuously monitored and specified indices of microvascular permeability (Kf an Pci) can be calculated, and 3) arterial, venous, and airway pressures can be adjusted independently to maintain the lobe in Zone 3. This preparation will also extend the observations regarding the effects of microemboli previously made in intact lung preparations. The specific aims are 1) to characterize the changes in permeability, vascular pressures, and cellular components of blood following microemboli, 2) to determine the protective effects of oxygen scavengers - superoxide dismutase (SOD), catalase (CAT), dimethylthiourea (DMTU), and dimethylsulfoxide (DMSO), 3) to describe the protective effects of granulocytopenia, 4) to observe the effects of allopurinol pretreatment and to correlate them with tissue levels of xanthine oxidase, and 5) to characterize the direct effects of oxygen radicals on the lung and the protective effects of oxygen scavengers. The lungs will be embolized with air bubbles (less than 1 mm in diameter), glass beads (50, 200, and 500 microns in diameter), and leukocyte aggregates (induced by complement activation) during normoxic and hypoxic conditions. It is anticipated that these studies will provide basic information regarding the role of oxygen radicals and their scavengers in injury due to microemboli as well as the role of oxygen radicals generated by xanthine oxidase in ischemic lung tissue.

成人呼吸窘迫综合征（ARDS）的特点是最初肺微血管系统的渗透性增加。在ARDS中，可能涉及白细胞血小板氧气自由基、胰头素、补体激活和血管内凝血和纤维蛋白溶解。血小板-纤维蛋白人和实验动物肺中的栓塞和白细胞抑制栓塞已经将注意力集中在微栓子上，并导致他们使用急性肺损伤的实验模型。虽然超氧化物的作用和其他氧自由基已被描述在氧毒性，其作用由于肺微血栓而造成的伤害很少受到关注这是本研究的总体目标。离体、灌注的狗肺标记将是基本的实验性标记。准备. 这种制剂的优点是：1）它灌注有全血及其所有成分，2）叶的重量是连续监测和规定的微血管通透性指数 (Kf可以计算Pci），以及3）动脉、静脉和气道可以独立地调节压力以将叶片保持在区域3中。这一准备工作还将扩大有关影响的意见，先前在完整肺制备物中制备的微栓子。具体目的是1）表征渗透性的变化，血管压力，以及微栓塞后血液的细胞成分， 2)确定氧清除剂-超氧化物的保护作用歧化酶（SOD）、过氧化氢酶（CAT）、二甲基硫脲（DMTU）和二甲基亚砜（DMSO），3）描述的保护作用，观察别嘌呤醇预处理对粒细胞减少症的影响，将它们与黄嘌呤氧化酶的组织水平相关联，以及5）表征氧自由基对肺的直接影响，氧清除剂的保护作用。肺部会被栓塞气泡（直径小于1 mm）、玻璃珠（50、200和500 和白细胞聚集体（由补体诱导活化）。预计这些研究将提供基本信息，关于氧自由基及其清除剂在损伤中的作用以及黄嘌呤产生的氧自由基的作用缺血肺组织中的氧化酶。