Prevention of Vein Graft Failure

描述(申请人提供)：人大隐静脉(HSV)是最常用的冠状动脉旁路移植术(CABG)和腹股沟下周围血管旁路移植术(PVBG)最有效的管道。然而，静脉移植失败的比率仍然很高(1-11年半时为45%)，目前还没有治疗方法被证明可以减少人类静脉移植失败。单纯疱疹病毒是从四肢采集并在植入前“准备”的。在这个过程中，外科医生通常会手动拉伸和扩张HSV，将管道储存在肝素化的生理盐水中，并在静脉上做标记，以防止植入时扭曲或扭结。这些动作会对导管的细胞成分造成严重的损伤，从而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的技术并不能充分保护移植的静脉。这一设想的假设是，在准备过程中，HSV细胞成分的损伤会导致内膜增生和静脉移植失败。这一假设的推论是，在手术准备时将损伤降至最低将影响随后的静脉移植物开放。这项建议将开发优雅简单的方法来预防移植物准备过程中的损伤，并促进我们对导致静脉移植物内膜增生的过程的理解。这一建议的潜在影响是开发出易于移植到临床的最佳静脉准备技术，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.