MECHANISMS OF DAMAGE CAUSED BY CARDIOPULMONARY BYPASS

体外循环造成损伤的机制

• 批准号: 3366410
• 负责人: STUART L COOPER
• 金额: $ 18.25万
• 依托单位: UNIVERSITY OF WISCONSIN-MADISON
• 依托单位国家: 美国
• 财政年份: 1991
• 资助国家: 美国
• 起止时间: 1991-08-01 至 1995-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3366410
• 关键词: antithrombogenic surface; arachidonate; biomaterial interface interaction; blood coagulation; blood proteins; cell adhesion; cell aggregation; complement; dogs; fibrinolysis; heart /lung bypass; leukocyte activation /transformation; leukocytes; monoclonal antibody; phagocytosis; platelets; polyethylenes; polymers; polyurethanes; protein purification; radiotracer; scanning electron microscopy; surface property; thrombosis; video recording system

Leukocytes, when exposed to activating stimuli, are capable of a wide variety of responses that are important in coagulation events. The interactions of these cells with other blood components such as proteins, blood factors, and platelets affect the amount of thrombus formation that occurs after damage to the vascular system. The biomaterial-blood interaction also initiates a series of coagulation events that result in artificial surface-induced thrombosis. Although extensive research has been done to determine the role of platelets and proteins in thrombus formation and embolization, there has been only limited study of how leukocytes modulate these responses. We propose to investigate the role of peripheral blood leukocytes in blood-material interactions in vitro by exposing the cells te biomaterials which have markedly different surface properties. The leukocyte responses of adherence, phagocytosis, degranulation, and expression of procoagulant and fibrinolytic activity will be assessed. In addition, the activation of complement by biomaterials, and subsequent leukocyte aggregation will be investigated. In parallel experiments, plasma proteins which have been shown to be relevant to biomaterial thrombogenicity will be preadsorbed onto the polymer surfaces before exposure to leukocytes to examine their effect on the leukocyte response. Leukocyte interactions with platelets as a result of arachidonic acid metabolism will be investigated to determine the role of this metabolite in the cellular enhancement of thrombogenesis. Canine ex vivo experiments will provide information about the acute and chronic reaction of leukocytes to implantation of a polymer material through measurement of leukocyte deposition and morphology. These studies of leukocyte responses and thrombus formation will lead to a better understanding of the mechanisms involved in artificial surface-induced thrombogenesis and will aid in the design of improved biocompatible polymeric materials.

白细胞暴露于激活刺激时，能够宽 在凝结事件中很重要的各种反应。 这 这些细胞与其他血液成分的相互作用，例如 蛋白质，血液因子和血小板会影响血栓的数量 损害血管系统后发生的形成。 生物材料血液相互作用还引发了一系列凝血 导致人造表面引起的血栓形成的事件。 虽然 已经进行了广泛的研究来确定血小板和 血栓形成和栓塞中的蛋白质仅存在 对白细胞如何调节这些反应的有限研究。 我们建议研究外周血白细胞在 通过暴露细胞TE，体外血液材料相互作用 具有明显不同的表面特性的生物材料。 这 依从性，吞噬作用，脱粒和的白细胞反应 将评估促凝剂和纤维蛋白水解活性的表达。 另外，生物材料的补体激活，以及 随后的白细胞聚集将进行研究。 在平行实验中，已证明为 与生物材料有关的血栓形成有关 暴露于白细胞之前的聚合物表面以检查其作用 在白细胞反应上。 白细胞相互作用与血小化酸相互作用。 将研究代谢以确定该代谢物的作用 在细胞增强血栓形成中。 犬离体实验将提供有关急性和 白细胞对聚合物材料植入的慢性反应 通过测量白细胞沉积和 形态学。 这些关于白细胞反应和血栓形成的研究将导致 更好地理解人造涉及的机制 表面诱导的血栓形成，将有助于设计 生物相容性聚合物材料。