Prevention of Vein Graft Failure

项目概要/摘要 人大隐静脉（HSV）是最常用的用于治疗的导管。 冠状动脉旁路移植术（CABG）和腹股沟下最有效的管道 外周血管旁路移植术（PVBG）。然而，静脉移植失败的几率 仍然很高（1-11/2年时为45%），目前没有治疗方法， 已经证明可以减少人体静脉移植失败。 HSV是从四肢采集的，并在植入前进行“准备”。期间 在这个过程中，外科医生通常手动拉伸和扩张HSV， 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 这导致内膜增生和静脉移植失败。 HSV代表移植到动脉中的自体器官 流通尽管在器官保存方面取得了许多进展，但目前的技术 用于制备和保存HSV的药物不能充分保护移植静脉。 这一建议的假设是，HSV细胞成分的损伤在HSV感染过程中可能是由HSV感染引起的。 制备导致内膜增生和静脉移植物失败。由此推论 假设在手术准备时尽量减少损伤将影响 随后静脉移植物通畅。这项提案将发展出优雅而简单的方法 以防止在移植物准备过程中发生损伤，并促进我们对 导致静脉移植物内膜增生的过程。 该提案的潜在影响是开发最佳静脉准备 可以容易地转化为临床从而降低发病率的技术， 死亡率和与静脉移植失败相关的费用。

Project summary/Abstract 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 failure.