MECHANISMS OF DAMAGE CAUSED BY CARDIOPULMONARY BYPASS

白细胞，当暴露于激活刺激时，能够广泛地 在凝血事件中重要的各种反应。 的 这些细胞与其他血液成分， 蛋白质、血液因子和血小板影响血栓的数量 在血管系统受损后形成。 生物材料与血液的相互作用也会引发一系列凝血 导致人工表面诱导血栓形成的事件。 虽然 已经进行了广泛的研究来确定血小板的作用， 蛋白质在血栓形成和栓塞中的作用， 白细胞如何调节这些反应的研究有限。 我们建议研究外周血白细胞在 体外血液-材料相互作用， 具有明显不同的表面性质的生物材料。 的 白细胞粘附、吞噬、脱粒反应， 将评估促凝血和纤溶活性的表达。 此外，生物材料对补体的激活， 随后将研究白细胞聚集。 在平行实验中，已被证明是 与生物材料促凝性相关的物质将被预吸附到 在接触白细胞之前， 对白细胞反应的影响 花生四烯酸引起的白细胞与血小板的相互作用 将研究代谢，以确定这种代谢物的作用 血栓形成的细胞增强。 犬离体实验将提供关于急性和慢性炎症的信息。 白细胞对植入聚合物材料的慢性反应 通过测量白细胞沉积， 形态学 这些白细胞反应和血栓形成的研究将导致 更好地理解人工智能的机制， 表面诱导的血栓形成，并将有助于设计改进的 生物相容性聚合物材料。

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.