ALCOHOL, ALCOHOLISM AND PLATELETS

酒精、酗酒和血小板

• 批准号: 2045840
• 负责人: ADAM K MYERS
• 金额: $ 8.05万
• 依托单位: GEORGETOWN UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1994
• 资助国家: 美国
• 起止时间: 1994-02-01 至 1996-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2045840
• 关键词: adenosine diphosphate; alcoholism /alcohol abuse; alcohols; erythrocytes; human tissue; laboratory mouse; physiology; platelet activating factor; platelet aggregation; prothrombin time

Effects of alcohol and alcoholism on blood platelets are of interest, owing to potential effects of alcohol on the incidence of cardiovascular disorders involving platelets, including thrombotic and hemorrhagic stroke, atherosclerosis, and myocardial infarction. The popular view is that although abuse is detrimental, moderate consumption might be beneficial, but this is not well documented. The effects of alcohol and alcohol consumption on platelet function have received substantial attention, with mixed results. In general, platelet function is inhibited when alcohol is consumed or added in vitro, and platelet aggregation is measured by conventional turbidometric techniques in platelet rich plasma or washed platelets. Other studies show platelet activation in these preparations by alcohol, however. Two shortcomings in this area of research have been the lack of systematic study of alcohol's effects on platelets using consistent techniques, and the lack of physiological preparations for the study of platelet function. For these reasons, we have conducted preliminary studies utilizing whole blood platelet aggregation techniques, which allow physiological interaction between platelets, other formed elements, and plasma constituents. These studies show remarkably different results depending on the mode of alcohol exposure. In vitro alcohol, at physiologically attainable levels, produces platelet aggregation in rat or human blood by inducing release of ADP from red blood cells, which then activates platelets in a Ca++ dependent manner. Limited preliminary experiments suggest that chronic, low dose in vivo exposure of rats to alcohol, analogous to mild intoxication and alcohol dependence, might inhibit aggregation induced by collagen. The hypothesis is that effects of alcohol on platelets are modulated by other formed elements in blood, and are dependent on dose and duration of exposure. The specific aims are to determine effects of acute and chronic alcohol in rats on platelet functional parameters and bleeding time in whole blood; to determine the role of ambient alcohol level, as opposed to exposure history, on platelet function and bleeding time; to critically evaluate the role of erythrocyte-platelet interactions on platelet functional effects of alcohol; and to evaluate the potential role of other formed elements on platelet effects of alcohol. These studies will be performed in rat models of acute and chronic alcohol consumption via inhalation, which results in a predictable level of blood alcohol, using ex vivo whole blood platelet aggregation techniques. In vitro studies will also be performed in human blood.

酒精和酗酒对血小板的影响很有趣， 由于酒精对心血管疾病发病率的潜在影响 涉及血小板的疾病，包括血栓性和出血性 中风、动脉粥样硬化和心肌梗塞。流行的观点是 尽管滥用是有害的，但适度消费可能是有益的 有益，但这没有很好的记录。酒精和酒精的影响 饮酒对血小板功能的影响显着 的关注，结果好坏参半。一般来说，血小板功能受到抑制 当在体外饮用或添加酒精时，血小板聚集 通过传统浊度技术在富含血小板的血浆中进行测量 或洗涤的血小板。其他研究表明这些中的血小板活化 然而，酒精制剂。这方面有两个不足 研究表明，缺乏对酒精对人体影响的系统研究。 血小板使用一致的技术，并且缺乏生理学 用于研究血小板功能的制剂。由于这些原因，我们 已经利用全血血小板进行了初步研究 聚合技术，允许之间的生理相互作用 血小板、其他有形成分和血浆成分。这些研究 根据酒精模式的不同，显示出明显不同的结果 接触。体外酒精在生理可达到的水平下会产生 通过诱导 ADP 释放，使大鼠或人血液中的血小板聚集 红细胞，然后激活 Ca++ 依赖性血小板 方式。有限的初步实验表明，慢性、低剂量 大鼠体内暴露于酒精，类似于轻度中毒和 酒精依赖，可能会抑制胶原蛋白诱导的聚集。这 假设酒精对血小板的影响受到其他因素的调节 血液中形成的元素，并且取决于剂量和持续时间 接触。具体目的是确定急性和慢性的影响 酒精对大鼠血小板功能参数和出血时间的影响 全血；确定环境酒精含量的作用，而不是 暴露史、血小板功能和出血时间；批判地 评估红细胞-血小板相互作用对血小板的作用 酒精的功能影响；并评估其他的潜在作用 有形成分对酒精对血小板的影响。这些研究将 在急性和慢性饮酒的大鼠模型中进行 吸入，导致可预测的血液酒精浓度，使用 离体全血血小板聚集技术。体外研究将 也可在人血中进行。