ACE Inhibition and Cardiac Allograft Vasculopathy

ACE 抑制和心脏同种异体移植血管病

• 批准号: 8070517
• 负责人: WILLIAM F FEARON
• 金额: $ 33.27万
• 依托单位: STANFORD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-05-01 至 2014-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8070517
• 关键词: Acetylcholine; Anatomy; Angiotensin II; Angiotensin II Receptor; Angiotensin-Converting Enzyme Inhibitors; Anterior Descending Coronary Artery; Anti-Inflammatory Agents; Anti-inflammatory; Arterial Fatty Streak; Arteries; Atherosclerosis; Bradykinin; Caliber; Cardiac; Cell Count; Clinical; Clinical Research; Complication; Coronary; Coronary Angiography; Coronary Arteriosclerosis; Coronary artery; Data; Development; Double-Blind Method; Endothelium-Dependent Relaxing Factors; Enzyme Gene; Evaluation; Event; Experimental Models; Fibrosis; Functional disorder; Genetic Polymorphism; Goals; Graft Survival; Health; Heart Transplantation; Heart failure; Immune response; Infection; Left; Left Ventricular Function; Measurement; Measures; Mediator of activation protein; Morbidity - disease rate; Nitric Oxide Synthase; Outcome; Oxidative Stress; Pathway interactions; Patients; Peptidyl-Dipeptidase A; Pharmaceutical Preparations; Physiological; Physiology; Placebos; Property; Prophylactic treatment; Ramipril; Randomized; Renin-Angiotensin System; Research Project Grants; Risk Factors; Role; Staging; Stem cells; Thrombosis; Transplant Recipients; Transplantation; Ultrasonography; Up-Regulation; Vascular Diseases; Vascular Proliferation; Vascular blood supply; Vascular remodeling; base; heart allograft; high risk; improved; improved functioning; interstitial; mortality; pilot trial; placebo controlled study; pressure; prevent; prospective; randomized trial; vascular inflammation

DESCRIPTION (provided by applicant): Cardiac transplantation is the ultimate treatment option for patients with end stage heart failure. Cardiac allograft vasculopathy remains a leading cause of morbidity and mortality after transplantation. Angiotensin converting enzyme inhibitors are used in less than one half of transplant recipients. Preliminary data suggest that angiotensin converting enzyme inhibitors retard the atherosclerotic plaque development that is the hallmark of cardiac allograft vasculopathy. Moreover, this class of drug appears to increase circulating endothelial progenitor cell number and has anti-inflammatory properties, both of which improve endothelial dysfunction, the key precursor to the development of cardiac allograft vasculopathy. The objective of this project is to investigate the role of an angiotensin converting enzyme inhibitor, ramipril, in preventing the development of cardiac allograft vasculopathy. During the first month after cardiac transplantation subjects will undergo coronary angiography with intravascular ultrasound measurements of plaque volume in the left anterior descending coronary artery. Using a coronary pressure wire, epicardial artery and microvascular physiology will be assessed. Finally, endothelial function and mediators of endothelial function, including circulating endothelial progenitor cells, will be measured. Subjects will then be randomized in a double blind fashion to either ramipril or placebo. After 1 year, the above assessment will be repeated. The primary endpoint will be the development of cardiac allograft vasculopathy based on intravascular ultrasound-derived parameters. The second aim will be to assess the effect of ramipril on endothelial dysfunction early after transplantation. The final aim is to determine the impact of ramipril on coronary physiology early after transplantation. PUBLIC HEALTH RELEVANCE: Heart transplantation remains an important treatment option for patients with heart failure. Unfortunately, many patients who undergo heart transplantation suffer and die because of the development of narrowings in the arteries supplying blood to the transplanted heart. The goal of this project is to investigate the ability of a drug called ramipril to prevent this significant complication.

描述（由申请人提供）： 心脏移植是终末期心力衰竭患者的最终治疗选择。心脏移植物血管病变仍然是移植后发病率和死亡率的主要原因。血管紧张素转换酶抑制剂用于不到一半的移植受者。初步数据表明，血管紧张素转换酶抑制剂延缓动脉粥样硬化斑块的发展，这是心脏移植物血管病变的标志。此外，这类药物似乎增加循环内皮祖细胞数量，并具有抗炎特性，这两者都改善了内皮功能障碍，这是心脏移植物血管病变发展的关键前兆。本项目的目的是研究血管紧张素转换酶抑制剂雷米普利在预防心脏移植物血管病变中的作用。在心脏移植后的第一个月期间，受试者将接受冠状动脉造影术，其中血管内超声测量左前降支冠状动脉中的斑块体积。将使用冠状动脉压力导丝评估心外膜动脉和微血管生理学。最后，将测量内皮功能和内皮功能介质，包括循环内皮祖细胞。然后将受试者以双盲方式随机分配至雷米普利或安慰剂组。1年后，将重复上述评估。主要终点将是基于血管内超声衍生参数的心脏移植物血管病变的发展。第二个目的是评估雷米普利对移植后早期内皮功能障碍的影响。最终目的是确定移植后早期雷米普利对冠状动脉生理的影响。公共卫生相关性：心脏移植仍然是心力衰竭患者的重要治疗选择。不幸的是，许多接受心脏移植的患者因为向移植心脏供血的动脉中的血栓而遭受痛苦和死亡。该项目的目标是研究一种名为雷米普利的药物预防这种严重并发症的能力。