AN INHIBITOR OF PLATELET ADHESION TO ARTIFICIAL SURFACE

血栓形成和凝血因子或有形成分的消耗 当血液与假肢接触时， 设备. 使用肝素和其他药理学试剂来最小化这些 不良反应. 在没有理想聚合物的情况下， 吸引血细胞，也不激活凝血，有几种方法已经 用于减少血液接触材料时的不良反应。 的 申请人已经证明了一个独特的存在 正常人血清中的白蛋白-免疫球蛋白G复合物（alb-IgG复合物）。 在体外分离状态下，该alb-IgG复合物显著抑制 血小板的粘附和某些血浆蛋白的吸附。 以来 涂有alb-IgG复合物的表面对血小板的吸引力较小， 申请人已经提出仔细检查这种蛋白质的作用 复杂的血液物质相互作用。 具体目标包括： 试图开发更好的纯化alb-IgG复合物的方法， 探索这种复合物是否可以在体外由白蛋白和IgG合成; 建立了一种用于定量alb-IgG复合物的方法，并检查了 正常血清和血液中的这种复合物的浓度 暴露于大表面积的材料;并通过以下方式研究其机理： 所述alb-IgG复合物抑制血小板粘附。 亲和层析 技术将被应用于发展一种有效的分离方法， 从血清中纯化alb-IgG复合物。 由于白蛋白和IgG出现 为了通过二硫键络合，硫醇试剂将用于 探索合成这种复合物的可能性。 一种合成的白蛋白-IgG复合物 具有粘附抑制性能的材料将是有用的，因为研究人员然后 不一定依赖于这种复合物的分离和纯化， 血清中存在少量（大于1 mg/ml）。 为了定量血清中的这种复合物，使用酶联免疫吸附法（ELISA）测定血清中的这种复合物。 将开发一种检测方法（ELISA）;已知白蛋白和IgG 该复合物中的部分与它们各自的抗体反应。 聚合物 将检查用alb-IgG复合物包被的表面的能力， 吸引血小板和白细胞以及它们启动凝血的能力， 血液-材料界面;这些实验将在 在流动室的帮助下体外和在离体颈-颈静脉 绵羊动静脉分流模型。 如果表面涂有alb-IgG 发现复合物的血栓形成较少，可以使用这种复合物。 用于改善假体装置的血液相容性的蛋白质复合物 接触血液。

Thrombosis and consumption of coagulation factors or formed elements of blood is often a consequence when blood comes in contact with a prosthetic device. Heparin and other pharmacologic agents are used to minimize these adverse reactions. In the absence of an ideal polymer that neither attracts blood cells nor activates clotting, several approaches have been taken to reduce adverse reactions when blood contacts a material. The applicants have demonstrated the presence of a unique albumin-immunoglobulin G complex (alb-IgG complex) in normal human serum. In an isolated state in vitro, this alb-IgG complex significantly inhibits the adhesion of platelets and adsorption of certain plasma proteins. Since surfaces coated with alb-IgG complex are less attractive to platelets, the applicants have proposed to carefully examine the effect of this protein complex on blood-material interaction. The specific aims include: attempts to develop better methods for purification of alb-IgG complex, and explore if this complex could be synthesized in vitro from albumin and IgG; develop a method for quantitation of alb-IgG complex and examine the concentration of this complex in normal serum and in patients whose blood is exposed to a large surface area of materials; and study the mechanism by which alb-IgG complex inhibits platelet adhesion. Affinity chromatographic techniques will be applied to evolve an efficient method for isolation and purification of alb-IgG complex from serum. Since albumin and IgG appear to be complexed via disulfide bond(s), thiol reagents will be used to explore possible synthesis of this complex. A synthetic alb-IgG complex with adhesion inhibitory property will be useful because investigators then do not have to depend on isolation and purification of this complex from serum in which it is present in small quantities (greater than 1 mg/ml). For quantitation of this complex in serum, an enzyme linked immunosorption assay (ELISA) will be developed; it is known that both albumin and IgG moieties in this complex react with their respective antibodies. Polymer surfaces coated with alb-IgG complex will be examined for their ability to attract platelets and leukocytes and their ability to initiate clotting at the blood-material interface; these experiments will be carried out in vitro with the help of a flow chamber and in ex vivo carotid-jugular Arterio-Venous shunt model in sheep. If surfaces coated with alb-IgG complex are found to be less thrombogenic, it may be possible to use this protein complex to improve the blood compatibility of prosthetic devices that contact blood.