MODULATION OF ENDOTHELIAL FUNCTION IN VASCULAR GRAFTS

血管移植物中内皮功能的调节

基本信息

批准号：
3472615
负责人：
VIRGINIA M MILLER
金额：
$ 11万
依托单位：
MAYO CLINIC ROCHESTER
依托单位国家：
美国
项目类别：
财政年份：
1989
资助国家：
美国
起止时间：
1989-04-01 至 1994-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/3472615
关键词：
adrenergic agents antithrombogenic surface arachidonate biomaterial interface interaction blood vessel transplantation cardiovascular prosthesis dogs electrostimulus human tissue perfusion platelet aggregation stimulant /agonist vascular endothelium vascular smooth muscle

项目摘要

The proposed studies will examine the function of the endothelium in biological and synthetic vascular grafts. In vitro techniques used to study endothelium-dependent responses in arteries and veins will be used to determine the functional state of the intima of autografts, allografts and of the neointima of synthetic vascular &rafts. A key question is whether the endothelium of veins implanted into the arterial circulation (vein grafts) produce and release factors in addition to metabolites of arachidonic acid which can modulate the tone of the underlying smooth muscle and act synergistically with prostacyclin to inhibit platelet aggregation. These experiments will identify the presence of chemical substances which could limit or promote thrombus formation, an important factor in limiting patency in vascular grafts. Other studies are designed to examine differences in the production and release of endothelium-derived factors in vein grafts implanted in the reverse and nonreverse (in situ) position and between vein grafts exposed chronically to low and high blood flows. These studies will identify physical factors which could alter endothelial function and therefore the patency of the grafts. It will be determined whether changes in responses of the vein grafts result from altered function of the endothelium or of the smooth muscle. By using selective inhibitors of receptors and enzymatic pathways, the mechanism of action of endothelium-derived factors will be determined. Similar studies will be performed on cryopreserved veins before and after implantation into the arterial circulation. Changes in endothelial function will be correlated with platelet adhesion to the cryopreserved allografts sequentially following implantation. The ability of the neointima of synthetic grafts to release endothelium-derived substance other than prostacyclin will be determined. The effectiveness of these substances to inhibit platelet aggregation will be compared between grafts seeded with endothelial cells of venous or arterial origin. It is anticipated that these experiments will identify particular deficits in the function of endothelial cells of vascular grafts which could lead to selected therapy to improve graft patency. They will provide new information crucial to understanding mechanisms associated with thrombus formation in and occlusion of vascular grafts.

拟议的研究将检查内皮的功能在生物和合成血管移植物中。体外技术用于研究动脉和静脉中的内皮依赖性反应将用于确定内膜的功能状态自体移植，同种异体移植和合成血管的新内膜＆筏。一个关键问题是静脉内皮是否植入动脉循环（静脉移植）产生的产生和释放因子除了花生四烯酸的代谢产物外它可以调节下面的平滑肌的音调并采取行动与前列环蛋白协同抑制血小板聚集。这些实验将确定化学物质的存在这可能限制或促进血栓形成，这是一个重要的限制血管移植物通畅的因素。其他研究是旨在检查生产和发布的差异植入反向的静脉移植物中的内皮衍生因子和非逆向（原位）位置以及静脉移植之间暴露长期至低血流动。这些研究会确定可能改变内皮功能的身体因素因此，移植物的通畅性。它将被确定静脉移植反应的变化是否因改变而导致内皮或平滑肌的功能。通过使用选择性抑制剂和酶促途径，内皮衍生因素的作用机理将是决定。将对冷冻保存进行类似的研究植入动脉循环前后的静脉。内皮功能的变化将与血小板相关对冷冻保存的同种异体移植的粘附依次遵循植入。合成移植物的新内膜的能力释放前列环蛋白以外的内皮衍生物质将可以确定。这些物质抑制的有效性将比较血小板聚集静脉或动脉起源的内皮细胞。预计这些实验将确定血管移植的内皮细胞的功能，可能导致以改善移植物通畅性的精选疗法。他们将提供对于理解与与之相关的机制至关重要的新信息血栓形成血管移植物和阻塞。