IN-VIVO EVALUATION OF SURFACE-INDUCED THROMBOGENESIS

表面诱导血栓形成的体内评估

• 批准号: 3337476
• 负责人: STUART L COOPER
• 金额: $ 20.9万
• 依托单位: UNIVERSITY OF WISCONSIN-MADISON
• 依托单位国家: 美国
• 财政年份: 1979
• 资助国家: 美国
• 起止时间: 1979-05-01 至 1988-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3337476
• 关键词: antithrombogenic surface; arteriovenous shunt surgery; biomaterial compatibility; biomaterial development /preparation; biomaterial evaluation; blood proteins; blood vessel prosthesis; cell adhesion; electron microscopy; flow cytometry; implant; photoelectron spectrometry; physical chemical interaction; platelets; polymers; polyurethanes; radiotracer; thrombosis

The occurrence of thrombosis at the blood-polymer interface presents major difficulties in the design of artificial organs and extracorporeal devices. Advances in the development of improved biomaterials could be realized through the use of improved testing methods and through a more complete understanding of the mechanism of surface-induced thrombogenesis. We have developed a sensitive in-vivo technique to measure transient thrombus deposition onto synthetic surfaces. Each polymer surface which we have studied to date has a unique protein and platelet deposition response during the 120 min. period of blood exposure evaluated. We propose to extend this in-vivo technique to include evaluation of blood-materials interactions in a newly developed series shunt model (10 materials - 120 min.), and a chronic model (1 material - 2+ wks.). Non-anticoagulated canine subjects will be utilized for all studies. Both of these applications employ radiolabeled platelets and proteins and extensive electron microscopic evaluation of deposited thrombi. The series shunt model allows short-term comparison and evaluation of up to 10 different surfaces simultaneously in the same animal. This more efficient technique will be utilized to correlate physical and chemical surface properties (i.e., polyurethane hard and soft segment type and composition, solvent composition, surface roughness effects, etc.) of polymeric biomaterials with their short-term in-vivo thrombogenic response. Chronic studies involving implantation of iliac A-V shunts in canine subjects, continuous blood-flow monitoring and laser-light scattering detection of shed emboli will provide a means for studying the long-term thrombogenic response of these polymeric biomaterials. The chronic and acute single-shunt models will be utilized to evaluate the role of proteins in artificial-surface induced thrombogenesis. Studies are planned to measure the in-vivo desorption and exchange of radiolabeled plasma proteins (fibronectin, albumin, IgG, fibrinogen, and Alpha-2 macroglobulin) from polymer surfaces over long-term periods, and to elucidate the role of various glycoproteins (transferrin, haptoglobin, ceruloplasmin, C3 complement, plasminogen) and "sugar-modified" (i.e., desialyated) proteins in initiating or diminishing thrombosis.

在血液-聚合物界面处血栓形成的发生呈现主要的 人工器官和体外循环设计中的困难 装置. 改进生物材料的开发进展可能是 通过使用改进的测试方法，并通过一个更 完全理解表面诱导血栓形成的机制。 我们已经开发了一种灵敏的体内技术来测量瞬态 血栓沉积在合成表面上。 每个聚合物表面， 迄今为止，我们已经研究了一种独特的蛋白质和血小板沉积反应， 在评价的120分钟血液暴露期间。 我们建议 将这种体内技术扩展到包括血液材料的评价 新开发的串联分流模型中的相互作用（10种材料-120 min.），和慢性模型（1种材料-2+周）。 非抗凝 犬受试者将用于所有研究。 这两 这些应用使用放射性标记的血小板和蛋白质， 沉积血栓的电子显微镜评价。 串联分流器 模型允许对多达10种不同的 同时出现在同一动物身上。 这种更有效的技术 将用于关联物理和化学表面性质 (i.e.,聚氨酯硬段和软段的类型和组成，溶剂 成分、表面粗糙度影响等）高分子生物材料 与它们的短期体内血栓形成反应有关。 慢性研究 涉及在犬受试者中植入髂动静脉分流管，连续 血流监测和脱落栓子的激光散射检测 将提供一种研究长期血栓形成反应的方法， 这些高分子生物材料。 慢性和急性单分流模型 将用于评估蛋白质在人工表面中的作用 诱导血栓形成。 计划进行研究以测量体内 放射性标记的血浆蛋白（纤连蛋白， 白蛋白、IgG、纤维蛋白原和α-2巨球蛋白 并阐明各种糖蛋白的作用 （转铁蛋白、触珠蛋白、血浆铜蓝蛋白、C3补体、纤溶酶原）和 “糖修饰的”（即，去唾液酸）蛋白质在启动或减少 血栓形成