EFFECT OF OMEGA-3 FATTY ACIDS IN CORONARY THROMBOSIS

最近的研究表明，血小板活化和 缺血性心脏病中的血栓形成。药理策略 正在进化以减少患者的血小板聚集 与冠状动脉疾病的关系，目的是减少 心肌梗死。另一种方法是补充 饮食中含有omega-3脂肪酸，已在 降低缺血性心脏发病率的流行病学研究 疾病。这项研究的目标是通过以下方式确定其机制 哪些omega-3脂肪酸延缓冠状动脉的发展 闭塞在体内冠状动脉血栓形成模型中的作用 与临床情况非常接近。体内5-羟色胺的释放 血小板聚集性将被用作血小板的体内指标 聚合。在狗身上会形成部分冠状动脉血栓 通过将电流施加到动脉管腔。停下来后 电流，血栓自发延伸以闭塞 动脉。将通过以下变化来评估血小板聚集： 经冠状静脉窦导管采集的血浆5-羟色胺水平。在……里面 活体血管反应性(血管运动)将通过 缝合在动脉壁上的微晶体。5-羟色胺将被检测 通过一种灵敏的放射酶方法。相关测量 将使用多普勒血流探头进行心肌功能检测， 长度段晶体(左心室收缩能力)，米勒 导管(血压)和心外膜心电图。狗将会是 鱼油前处理12周及其对时间的影响 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。选定的代理将是 用于确定omega-的作用部位和作用机制 3种脂肪酸。这些实验的主旨是确定 喂食鱼油如何改变脑组织的自发伸展 先前存在的血栓导致冠状动脉闭塞，而不是 调查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 活体模型中的实验可以定量评估 血小板聚集、血栓形成和血管反应性。

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.