Prevention of Vein Graft Failure

描述（由申请人提供）：人大隐静脉（HSV）是冠状动脉旁路移植术（CABG）最常用的管道，也是腹股沟下外周血管旁路移植术（PVBG）最有效的管道。然而，静脉移植失败的发生率仍然很高（1-11/2年时为45%），目前还没有显示出减少人类静脉移植失败的治疗方法。HSV是从四肢采集的，并在植入前进行“准备”。在此过程中，外科医生通常手动拉伸和扩张HSV，将导管储存在肝素化盐水中，并标记静脉以防止植入时扭曲或扭结。这些操作会对导管的细胞成分造成严重损伤，导致内膜增生和静脉移植失败。HSV代表移植到动脉循环中的自体器官。尽管在器官保存方面取得了许多进展，但目前用于制备和保存HSV的技术不能充分保护移植静脉。该建议的假设是，在制备过程中对HSV的细胞成分的损伤导致内膜增生和静脉移植失败。该假设的推论是，手术准备时尽量减少损伤将影响随后的静脉移植物通畅性。这项建议将发展优雅简单的方法，以防止在移植准备过程中的损伤，以及促进我们的理解的过程中，导致静脉移植内膜增生。该提案的潜在影响是开发最佳的静脉准备技术，这些技术可以很容易地转化为临床，从而降低与静脉移植失败相关的发病率、死亡率和成本。

DESCRIPTION (provided by applicant): Human greater saphenous vein (HSV) is the most commonly used conduit for coronary artery bypass grafting (CABG) and the most effective conduit for infrainguinal peripheral vascular bypass grafting (PVBG). However, the rate of vein graft failure remains high (45% at 1-11/2 years) and there is no current therapeutic approach that has yet been shown to reduce vein graft failure in humans. HSV is harvested from the extremity and "prepared" prior to implantation. During this process, surgeons typically manually stretch and distend the HSV, store the conduit in heparinized saline, and mark the vein to prevent twisting or kinking on implantation. These maneuvers cause significant injury to the cellular components of the conduit which leads to intimal hyperplasia and vein graft failure. HSV represents an autologous organ that is transplanted into the arterial circulation. Despite the many advances in organ preservation, the current techniques used to prepare and preserve HSV do not adequately protect the transplanted vein. The hypothesis of this proposal is that injury to the cellular components of HSV during preparation lead to intimal hyperplasia and vein graft failure. The corollary to this hypothesis is that minimizing injury at the time of surgical preparation will impact subsequent vein graft patency. This proposal will develop elegantly simple approaches to prevent injury during graft preparation as well as promote our understanding of the processes that lead to vein graft intimal hyperplasia. The potential impact of this proposal is to develop optimal vein preparation techniques that can be readily translated into the clinic thus reducing the morbidity, mortality, and costs associated with vein graft failur.