Enhancing vein graft viability

描述（由申请人提供）：每年使用人隐静脉（HSV）进行约1,000,000例冠状动脉和周围血管重建术。移植物失败的主要原因是随后发生的内膜增生。通常用于HSV采集的外科技术会造成损伤。这些有害的技术包括拉伸静脉（在收获时纵向拉伸和通过手动高压腔内扩张），在收获后放置静脉肝素化盐水（pH值6.2），以及使用外科皮肤标记物（含有异丙醇）涂抹在静脉上以正确定位静脉移植物。初步数据显示，40%的冠状动脉旁路手术采集的HSV没有功能生存能力。该建议的假设是，在收获期间防止静脉损伤将减少内膜增生的后续发展。该建议将1)确定静脉移植物功能活力丧失的机制；2)确定兔颈动脉间置静脉移植损伤是否导致血管内膜增生。虽然许多研究者认为损伤对导管是有害的，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来提高移植物的通畅性。这将对与静脉移植失败相关的发病率、死亡率和费用产生重大影响。

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. PUBLIC HEALTH RELEVANCE: Cardiovascular disease is one of the leading causes of death and disability in the United States. Our research could potentially increase the time a bypass graft stays open, and lessen the morbidity and mortality of vein graft failure.