EFFECT OF OMEGA-3 FATTY ACIDS IN CORONARY THROMBOSIS

OMEGA-3 脂肪酸在冠状动脉血栓形成中的作用

• 批准号: 3355819
• 负责人: CLAUDE R BENEDICT
• 金额: $ 17.74万
• 依托单位: UNIVERSITY OF TEXAS MED BR GALVESTON
• 依托单位国家: 美国
• 财政年份: 1987
• 资助国家: 美国
• 起止时间: 1987-07-01 至 1990-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3355819
• 关键词: acute disease /disorder; adenosine diphosphate; chronic disease /disorder; coronary artery; coronary disorder; coronary occlusion /thrombosis; diet therapy; dietary supplements; disease /disorder model; disease /disorder prevention /control; dogs; eicosanoid metabolism; electrocardiography; electrostimulus; epinephrine; gas chromatography; heart catheterization; high performance liquid chromatography; histamine; histology; ionophores; marine animal oil; microelectrodes; model design /development; myocardial infarction; myocardium; nutrition related tag; omega 3 fatty acid; platelet aggregation; platelet aggregation inhibitors; prostacyclins; radioassay; radioimmunoassay; receptor; scanning electron microscopy; serotonin; thromboxanes; ultrasound blood flow measurement; vascular endothelium; vasoactive agent; vasoconstriction; vasodilation

Recent studies show the importance of platelet activation and thrombosis in ischemic heart disease. Pharmacological strategies are being evolved to decrease platelet aggregation in patients with coronary disease with the aim of reducing the incidence of myocardial infarction. An alternate approach is to supplement the diet with omega-3 fatty acids which have been shown in epidimiological studies to lower the incidence of ischemic heart disease. The goal of this study is to determine the mechanisms by which omega-3 fatty acids delay the development of coronary occlusion in an in vivo model of coronary thrombosis that more closely mimics the clinical situation. Serotonin release during platelet aggregation will be used as an in vivo index of platelet aggregation. A partial coronary thrombus will be formed in dogs by application of current to the arterial lumen. After stopping the current, thrombus spontaneously extends to occlude the artery. Platelet aggregation will be assessed by changes in plasma serotonin levels drawn via coronary sinus catheters. In vivo vascular reactivity (vasomotion) will be measured by microcrystals sewn to the arterial wall. Serotonin will be assayed by a sensitive radioenzymatic method. Correlative measurements of myocardial functions will be made using Doppler flow probes, length segment crystals (left ventricular contractility), Millar catheters (blood pressure), and epicardial ECGs. Dogs will be pretreated with fish oil for 12 weeks and its effect on time for thrombotic occlusion, in vivo and in vitro platelet aggregation, vascular reactivity, platelet and vessel wall thromboxane, and prostacyclin synthesis will be determined. Selected agents will be used to determine the site and the mechanism of action of omega- 3 fatty acids. The thrust of these experiments is to determine how fish oil feeding may alter the spontaneous extension of a preexisting thrombus leading to coronary occlusion, not to investigate the initial events associated with thrombogenesis. Preliminary studies show the feasibility of accomplishing these experiments in an in vivo model that can quantitatively assess platelet aggregation, thrombus formation, and vascular reactivity.

最近的研究表明血小板活化的重要性， 缺血性心脏病血栓形成 药理学策略 正在发展以减少患者的血小板聚集 目的是降低冠心病的发病率， 心肌梗死 另一种方法是补充 含有omega-3脂肪酸的饮食， 降低缺血性心脏病发病率的流行病学研究 疾病 本研究的目的是确定机制， 哪种欧米茄-3脂肪酸可以延缓冠状动脉的发展 闭塞在冠状动脉血栓形成的体内模型中， 非常接近临床情况。 血清素释放 血小板聚集将用作血小板的体内指标 聚合来 在犬中会形成部分冠状动脉血栓 通过向动脉腔施加电流。 停止后 当前血栓自发地延伸以阻塞 动脉 血小板聚集将通过以下指标的变化进行评估： 通过冠状窦导管抽取血浆血清素水平。 在 体内血管反应性（血管运动）将通过以下方法测量： 缝在动脉壁上的微晶体 将测定血清素 通过灵敏的放射酶法。 相关测量 将使用多普勒血流探头， 长度节段晶体（左心室收缩性），Millar 导管（血压）和心外膜心电图。 狗将被 用鱼油预处理12周， 血栓闭塞，体内和体外血小板聚集， 血管反应性、血小板和血管壁血栓素，以及 将测定前列环素的合成。 选定的代理人将 用于确定欧米茄的作用部位和机制， 3脂肪酸。 这些实验的目的是确定 鱼油喂养如何改变自发的 预先存在的血栓导致冠状动脉闭塞，而不是 研究与血栓形成相关的初始事件。 初步研究表明，实现这些目标是可行的。 在体内模型中进行的实验可以定量评估 血小板聚集、血栓形成和血管反应性。