THROMBOSIS ON BIOMATERIALS--VASCULAR COMPONENTS

生物替代品有限的问题， 大多数血管和器官的功能衰竭会加剧病变。 假体植入物和器官替代品， 血栓栓塞事件。 其背后的机制 血栓块在生物材料表面上的沉积 明白 本建议的目的是 研究血管表面对沉积的影响， 血小板和纤维蛋白。 管状 灌注室已被开发用于安装材料 紧接着受损血管表面的下游， 在离体灌注系统中将复合基质与血液混合。 将使用猪和人类受试者的血液， 研究重要的具体机制， 测定血栓物质在血管上的沉积， 生物材料表面 表面沉积物的评估将 通过几种技术进行。 在猪中，III-In标记 将注射血小板，并确定沉积的血小板数量。 放射性测定。 在猪和人类中，形态测量 将利用环氧树脂嵌入半薄切片的分析， 定量血小板和纤维蛋白沉积。 血栓沉积物将 对几个暴露时间、从 近端表面和壁剪切速率，使得 研究了流动条件的生理范围（壁面剪切 速率从50-5000秒-1）。 近端（血管）和远端（生物材料）表面的变化 血液的状况将被用来探索 血小板和纤维蛋白在假体上沉积的机制 面 血管壁的各种成分，包括， 内皮下及其修饰、胶原和组织因子 将用作激活近端表面。 血液从 患有各种出血性疾病的患者和动物模型将被 用于研究血管性血友病因子的重要性， 血小板糖蛋白Ib和IIb-IIIa，血小板释放产物 以及凝血因子Xi、凝血和凝血因子的相对重要性。 组织因子、因子VII、IX途径。 VWF抗体，和 糖蛋白Ib和IIb-IIIa也将被采用和比较 与用相应的天然存在的 缺陷 血栓沉积物生长的机制也将被讨论。 在非流线（再循环）流动中， 修改灌注室和粒子理论 沉积将被开发。

The problem of limited availability of biological replacements for diseased vessels and organs is exacerbated by the failure of most prosthetic implants and organ substitutes due to repeated thrombo-embolic events. The mechanism which underlie the deposition of thrombotic masses on biomaterial surfaces is poorly understood. The objective of the present proposal is to investigate the influence of vascular surfaces on the deposition of platelets and fibrin on selected prosthetic surfaces. A tubular perfusion chamber has been developed for mounting the materials immediately downstream of injured vascular surfaces exposing the composite substrates to blood in an ex vivo perfusion system. Blood from both swine and human subjects will be utilized to investigate the specific mechanisms which are important in determining the deposition of thrombotic material on the biomaterial surface. Evaluation of the surface deposits will be performed by several techniques. In swine, III-In labelled platelets will be injected and the quantity of deposited radioactivity determined. In swine and humans, morphometric analysis of epoxy embedded semi-thin sections will be utilized to quantify platelet and fibrin deposits. The thrombotic deposits will be evaluated for several exposure times, axial positions from the proximal surface and wall shear rates, such that the full physiological range of flow conditions is investigated (wall shear rates from 50-5000 sec-1). Variation of proximal (vascular) and distal (biomaterial) surfaces and the condition of the blood will utilized to explore the mechanisms of platelet and fibrin deposition on the prosthetic surface. Various components of the vessel wall, including, subendothelium and its modifications, collagen, and tissue factor will be utilized as the activating proximal surface. Blood from patients and animal models with various bleeding disorders will be utilized to investigate the importance of von Willebrand factor, platelet glycoproteins Ib and IIb-IIIa, platelet released products and the relative importance of the Factor XI, coagulation and the tissue factor, Factor VII, IX pathways. Antibodies of VWF, and glycoproteins Ib and IIb-IIIa will also be employed and compared to results obtained with the corresponding naturally occurring deficiency. The mechanisms of growth of thrombotic deposits will also be investigated in nonstreamline (recirculation) flow by appropriately modifying the perfusion chambers and a theory for particle deposition will be developed.