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细胞的功能用于生物和合成血管移植物。体外技术用于研究动脉和静脉的内皮依赖性反应将用于确定内膜的功能状态自体移植物、同种异体移植物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（静脉移植物）产生和除花生四烯酸代谢物外的释放因子它可以调节底层平滑肌的张力并发挥作用与前列环素协同作用，抑制血小板聚集。这些实验将识别化学物质的存在这可以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。其他研究有旨在检查生产和发布的差异反向植入静脉移植物中的内皮衍生因子和非反向（原位）位置以及暴露的静脉移植物之间长期出现低血流和高血流。这些研究将识别可能改变内皮功能的物理因素因此移植物的通畅性。将会确定静脉移植反应的变化是否是由于改变引起的内皮或平滑肌的功能。通过使用受体和酶途径的选择性抑制剂内皮衍生因子的作用机制是决定。类似的研究将在冷冻保存的植入动脉循环之前和之后的静脉。内皮功能的变化与血小板相关随后对冷冻保存的同种异体移植物的粘附植入。合成移植物的新内膜的能力释放除前列环素以外的内皮衍生物质被确定。这些物质的抑制效果将比较接种的移植物之间的血小板聚集静脉或动脉来源的内皮细胞。预计这些实验将识别出特定的缺陷血管移植物内皮细胞的功能可能导致选择治疗以改善移植物通畅。他们将提供新信息对于理解相关机制至关重要血管移植物中的血栓形成和闭塞。