Enhancing vein graft viability

描述(申请人提供)：每年使用人类大隐静脉(HSV)进行大约1,000,000例主动脉-冠状动脉和外周血管再血管化手术。移植物失败的主要原因是随后发生的内膜增生。通常用于采集HSV的外科技术会造成伤害。这些损伤性技术包括(在收获期间纵向和通过手动高压腔内扩张)拉伸静脉，在收获后放置肝素化生理盐水(pH 6.2)，以及使用外科皮肤标记物在静脉上涂抹(含有异丙醇)以正确定位静脉移植物。初步数据显示，用于冠状动脉搭桥术的HSV中有40%没有功能可行性。这一建议的假设是，在采收过程中防止静脉损伤将减少随后发生的内膜增生。这项建议将1)确定静脉移植物功能活性丧失的机制；2)确定静脉移植物的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，采用简单、直接的干预措施，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、死亡率和成本产生重大影响。

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.