PRESERVATION OF ENDOTHELIAL DEPENDENT RELAXATION

保护内皮依赖性舒张

• 批准号: 8442056
• 负责人: Colleen M Brophy
• 金额: --
• 依托单位: VETERANS HEALTH ADMINISTRATION
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-04-01 至 2017-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8442056
• 关键词: Adhesions; Affect; Anti-Inflammatory Agents; Anti-inflammatory; Arterial Fatty Streak; Atherosclerosis; Attention; Autologous; Back; Bathing; Behavior; Biochemical Markers; Biological Preservation; Blood Circulation; Blood Vessels; Bypass; Cardiac; Cardiovascular Diseases; Cardiovascular system; Cell Adhesion Molecules; Cell Survival; Cellular Stress; Cessation of life; Clinic; Clinical; Coronary Arteriosclerosis; Coronary Artery Bypass; Data; Development; Endothelial Cells; Endothelium; Failure; Family suidae; Future; Goals; Growth; Harvest; Histologic; Human; Hyperplasia; Induced Heart Arrest; Inflammation; Inflammatory; Injury; Intervention; Investigation; Knowledge; Lead; Leukocytes; Limb Salvage; Limb structure; Lower Extremity; Modeling; Morbidity - disease rate; Muscle; Myocardial Infarction; Nitric Oxide; Operative Surgical Procedures; Organ; Organ Culture Techniques; Organ Preservation; Organ Transplantation; Outcome; Oxidative Stress; Pathogenesis; Patients; Peripheral; Peripheral Vascular Diseases; Platelet Activation; Preparation; Preservation Technique; Procedures; Process; Recurrence; Relaxation; Research; Resources; Role; Saline; Saphenous Vein; Skin; Smooth Muscle; Solutions; Surgeon; Techniques; Translating; Transplantation; United States; Veins; Work; cost; effective therapy; graft failure; high throughput screening; implantation; improved; in vivo; migration; monolayer; mortality; operation; pressure; prevent; public health relevance; reconstruction; response; response to injury; vascular smooth muscle cell proliferation

DESCRIPTION (provided by applicant): Cardiovascular diseases are the leading cause of morbidity and mortality in the United States and are responsible for one out of every five deaths. Coronary artery bypass grafting (CABG) is one of the most effective treatments for advanced coronary artery disease (CAD) and peripheral bypass grafting (PBG) for the treatment of limb salvage in peripheral vascular disease. The most common conduit used to bypass stenotic and occlusive atherosclerotic lesions is the saphenous vein. The saphenous vein (HSV) is harvested from the lower extremity and prepared for use as an arterial conduit. As such, the HSV represents an autologous transplanted "organ" and little attention has been directed at organ preservation of the HSV. The leading cause of HSV failure is the development of intimal hyperplasia, a response to injury. The hypothesis of this investigation is that reducing injury to the HSV during harvest and preparation will preserve endothelial function and the salutary effects of the endothelium (antithrombotic, anti-inflammatory, and growth-inhibitory effects on the smooth muscle). The specific aims of this investigation are to: #1: Optimize techniques to preserve HSV endothelial function during surgical harvest and preparation; and #2: Determine if optimizing endothelial function during preparation reduces the development of intimal hyperplasia. HSV represents a unique opportunity for intervention in that the vein represents an autologous transplant organ. While significant research effort has pursued myocardiac preservation (cardioplegia) during cardiac revascularization, very little attention has been given to preservation of the conduit used for the arterial reconstruction, the HSV. This work will enhance our understanding of the pathogenesis of vein graft failure, improve preservation of the vein graft during harvest and preparation, and modify surgeon behavior in terms of treating the conduit as a transplanted organ that requires careful preservation. The goal of this proposal is to develop approaches to enhance HSV functional cellular viability and demonstrate that these approaches ameliorate intimal hyperplasia. The potential impact of this proposal will enhance our understanding of the role of injury during current graft preparation techniques on the subsequent development of intimal hyperplasia. This proposal will also develop optimal vein preparation techniques that can be readily translated into the clinic. Future directions will determine if optimizing preservation techniques and endothelial function of HSV will improve clinical outcomes following CABG and peripheral bypass procedures. Preventing endothelial injury during harvest represents a simple, straight forward approach to reduce the morbidity, mortality, and costs associated with vein graft failure.

描述（由申请人提供）： 心血管疾病是美国发病率和死亡率的主要原因，每五例死亡中就有一例是由心血管疾病引起的。冠状动脉旁路移植术（CABG）是治疗晚期冠状动脉疾病（CAD）最有效的方法之一，外周血管旁路移植术（PBG）是治疗外周血管疾病的保肢方法。最常见的用于旁路狭窄和闭塞性动脉粥样硬化病变的管道是隐静脉。从下肢采集隐静脉（HSV），准备用作动脉导管。因此，HSV代表自体移植的“器官”，并且很少关注HSV的器官保存。 HSV失败的主要原因是内膜增生的发展，这是对损伤的反应。 本研究的假设是，在收获和制备过程中减少对HSV的损伤将保护内皮功能和内皮的有益作用（抗血栓形成、抗炎和对平滑肌的生长抑制作用）。本研究的具体目的是：#1：优化技术以在手术采集和准备期间保护HSV内皮功能;#2：确定在准备期间优化内皮功能是否减少内膜增生的发展。HSV代表了一个独特的干预机会，因为静脉代表自体移植器官。 虽然在心脏血管重建期间已经进行了大量的研究工作来进行心肌保存（心脏停搏液），但是很少关注用于心脏血管重建的管道的保存。 动脉重建HSV这项工作将提高我们对静脉移植失败的发病机制的理解，提高静脉移植物在收获和准备过程中的保存，并修改外科医生的行为，在治疗管道作为一个移植器官，需要仔细保存。本提案的目标是开发提高HSV功能性细胞活力的方法，并证明这些方法可改善内膜增生。该建议的潜在影响将增强我们对当前移植物制备技术过程中损伤对随后内膜增生发展的作用的理解。该提案还将开发最佳的静脉准备技术，可以很容易地转化为临床。未来的方向将确定优化保存技术和HSV的内皮功能是否会改善CABG和外周旁路手术后的临床结局。在采集过程中防止内皮损伤是一种简单、直接的方法，可以降低与静脉移植失败相关的发病率、死亡率和成本。