Prevention of Vein Graft Failure

预防静脉移植失败

基本信息

批准号：
8974847
负责人：
Colleen M Brophy
金额：
$ 0.75万
依托单位：
VANDERBILT UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2003
资助国家：
美国
起止时间：
2003-04-01 至 2016-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8974847
关键词：
Acute Anti-Inflammatory Agents Anti-inflammatory Apoptosis Autologous Biological Process Blood Circulation Blood Vessels Bypass Cell physiology Cessation of life Clinic Coronary Artery Bypass Development Endothelium Event Extracellular Matrix Proteins Goals Harvest Health Human Hyperplasia Injury Lead Limb structure Mechanics Modeling Morbidity - disease rate Muscle function Myocardial Infarction Operative Surgical Procedures Organ Organ Preservation Organ Transplantation Patients Peripheral Post-Translational Protein Processing Preparation Prevention Process Production Property Reactive Oxygen Species Recurrence Saline Saphenous Vein Signal Transduction Skin Smooth Muscle Smooth Muscle Myocytes Stretching Surgeon Techniques Therapeutic Therapeutic Intervention Time Translating Transplantation Vein graft Veins cost graft failure implantation migration mortality operation prevent response response to injury senescence

项目摘要

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.

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）最常用的导管，也是腹股沟下外周血管旁路移植术（PVBG）最有效的导管。然而，静脉移植失败率仍然很高（1-11/2 年为 45%），并且目前尚无任何治疗方法可被证明可以减少人类静脉移植失败。 HSV 从四肢采集并在植入前进行“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，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 的技术并不能充分保护移植的静脉。该提议的假设是，在制备过程中HSV细胞成分的损伤导致内膜增生和静脉移植失败。这一假设的推论是，在手术准备时尽量减少损伤将影响随后的静脉移植物的通畅。该提案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过程的理解。该提案的潜在影响是开发最佳的静脉准备技术，该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。