Enhancing vein graft viability

增强静脉移植物的活力

• 批准号: 8320260
• 负责人: Michael James Osgood
• 金额: $ 4.94万
• 依托单位: VANDERBILT UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-09-01 至 2013-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8320260
• 关键词: Apoptosis; Blood Vessels; Bypass; Cardiovascular Diseases; Cause of Death; Clinical Trials; Coronary Artery Bypass; Cytolysis; Data; Deposition; Development; Dyes; Evaluation; Exposure to; Extracellular Matrix; FDA approved; Family suidae; Future; Goals; Government; Harvest; Human; Hyperplasia; Injury; Intervention; Isopropanol; Manuals; Mechanics; Membrane; Modeling; Morbidity - disease rate; Neurologic; Operative Surgical Procedures; Oryctolagus cuniculus; Outcome; P2X-receptor; Peripheral; Persons; Procedures; Purinoceptor; Rattus; Receptor Activation; Recovery; Research; Research Personnel; Saline; Saphenous Vein; Skin; Smooth Muscle; Spinal cord injury; Stretching; Techniques; Therapeutic; Time; Tissues; United States; Veins; analog; cost; disability; functional disability; functional loss; graft failure; graft function; improved; in vivo; migration; mortality; pre-clinical; pressure; prevent; receptor; response; response to injury

DESCRIPTION (provided by applicant): Approximately 1,000,000 aortocoronary and peripheral vascular revascularizations are performed each year using human saphenous vein (HSV). The leading cause of graft failure is the subsequent development of intimal hyperplasia. Surgical techniques typically employed for HSV harvest cause injury. These injurious techniques include stretching the vein (longitudinally during harvest and by manual high-pressure intraluminal distension), placing the vein heparinized saline (pH 6.2) after harvest and the use of surgical skin markers applied to the vein (which contain isopropyl alcohol) to properly orient the vein graft. Preliminary data has shown that 40% of HSV harvested for coronary artery bypass procedures have no functional viability. The hypothesis of this proposal is that preventing injury to the vein during harvest will decrease the subsequent development of intimal hyperplasia. This proposal will 1) determine the mechanisms underlying the loss of functional viability of vein grafts; 2) determine if injury to the vein graft leads to the development of intimal hyperplasia in a rabbit carotid interposition vein graft model. While many investigators have suggested that injury is deleterious to the conduit, this notion has not been proven in vivo. Accomplishment of these goals would provide a platform for future clinical trials with simple straightforward interventions that would improve graft patency. This would have a significant impact on the morbidity, mortality, and costs associated with vein graft failure.

描述（由申请人提供）：每年使用人隐静脉（HSV）进行约1，000，000例冠状动脉和外周血管血运重建。移植物失败的主要原因是内膜增生的后续发展。通常用于HSV收获的手术技术会导致损伤。这些有害技术包括拉伸静脉（在采集过程中纵向拉伸和手动高压腔内扩张），采集后放置静脉肝素化盐水（pH 6.2），以及使用应用于静脉的外科皮肤标记（含有异丙醇）以正确定向静脉移植物。初步数据表明，40%的HSV收集冠状动脉搭桥手术没有功能的活力。该建议的假设是，在采集过程中防止对静脉的损伤将减少内膜增生的后续发展。该提案将1）确定静脉移植物功能活力丧失的潜在机制; 2）确定静脉移植物损伤是否导致兔颈动脉间置静脉移植物模型中内膜增生的发展。虽然许多研究人员认为损伤对管道有害，但这一观点尚未在体内得到证实。这些目标的实现将为未来的临床试验提供一个平台，通过简单直接的干预措施改善移植物通畅性。这将对与静脉移植失败相关的发病率、死亡率和成本产生重大影响。