HEPARINIZED MATERIALS - BLOOD INTERACTIONS

肝素化材料 - 血液相互作用

• 批准号: 3337472
• 负责人: MICHAEL V SEFTON
• 金额: $ 6.05万
• 依托单位: UNIVERSITY OF TORONTO
• 依托单位国家: 美国
• 财政年份: 1985
• 资助国家: 美国
• 起止时间: 1985-09-30 至 1989-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3337472
• 关键词: antithrombin III; antithrombogenic surface; biomaterial development /preparation; biomaterial interface interaction; blood vessel prosthesis; cardiovascular shunt surgery; cell adhesion; enzyme complex; heparin; immobilized enzymes; platelet activating factor; platelet aggregation; polyethylenes; polyvinyls; radiotracer; thrombin; tissue /cell culture

Detailed examination of the mode of action and fate of surface bound heparin is important to the assessment of the oft-stated but never proven concerns regarding the use of heparin in long term implants: 1) the necessity for a heparin microenvironment 2) saturation of bound heparin 3) consumption of blood components 4) enhanced platelet disposition. Work to date has shown that heparin immobilized on polyvinyl alcohol by glutaraldehyde crosslinking (heparin-PVA) need not be lost from the surface to impart thrombo-resistance to the PVA or underlying substrate as measured by various in vitro assays and in a novel AV shunt model in dogs. Furthermore the bound thrombin-antithrombin III inactive complex is readily displaced from the surface by plasma (yielding post-complex antithrombin III and presumably post-complex thrombin) indicating that the surface bound heparin does not become saturated with inactive complex. Platelet interactions appear to be more complex and these are the primary focus of this proposal. The platelet compatibility of heparin-PVA coated polyethylene tubing will be compared with that of control PVA tubing without heparin in a chronic shunt in dogs, by measuring the platelet consumption rate and by measuring the platelet deposition profile as a function of time at low flowrates in our parallel flow shunt. This ex vivo compatibility and the previously determined in vitro response of platelets will be compared with that observed for PVA surfaces which have been modified by immobilization of polyethylene glycol, or PGE1 or PGE2 with the intention of reducing the platelet reactivity of the substrate. Also the potential to "neutralize" or "bypass" the immobilized heparin will be studied, the in vitro displacement behaviour of bound thrombin will be subject to further clarification and the dose effect relationship for immobilized heparin will be determined in the parallel flow AV shunt model. The potential thromboresistance of heparinized materials warrants these detailed investigations. With this information it may be possible to use heparinized materials in the cardio-circulatory assist devices and blood handling procedures that await the development of blood compatible materials.

详细检查作用方式和表面结合的命运 肝素对于评估常规但从未证明很重要 长期植入肝素使用的担忧：1） 肝素微环境的必要性2）结合肝素3的饱和度） 血液成分的消耗4）增强的血小板处置。 迄今为止的工作表明，肝素固定在聚乙烯醇上 戊二醛交联（肝素-PVA）无需从表面丢失 按照测量 通过各种体外测定，在狗的新型AveNunt模型中。 此外，结合的凝血酶 - 抗凝血酶III很容易复合 血浆从表面移位（产生复合后抗凝血酶 iii和大概在复合后凝血酶）表示表面结合 肝素不会被非活性复合物饱和。 血小板 互动似乎更复杂，这些是 这个建议。 肝素-PVA涂层聚乙烯管的血小板兼容性将 与对照PVA管的持续性PVA管的慢性相提并论 通过测量血小板消耗率和测量 血小板沉积曲线随着低流量的时间的函数 我们的平行流量分流。 这种离体的兼容性和以前的兼容性 确定血小板的体外反应将与 观察到通过固定的PVA表面已修改的PVA表面 聚乙烯乙二醇，或PGE1或PGE2，目的是减少 底物的血小板反应性。 也有可能“中和” 或“绕过”固定的肝素，体外 绑定凝血酶的位移行为将进一步进行 固定肝素的澄清和剂量效应关系将 可以在平行流动线模型中确定。 肝素化材料的潜在血栓形成保留这些 详细的调查。 有了这些信息，可能可以使用 心脏循环辅助设备和血液中的肝素化材料 处理血液兼容的过程的处理程序 材料。