ACE Inhibition and Cardiac Allograft Vasculopathy

ACE 抑制和心脏同种异体移植血管病

• 批准号: 8259175
• 负责人: WILLIAM F FEARON
• 金额: $ 32.94万
• 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/8259175
• 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; 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

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.

心脏移植是终末期心力衰竭患者的最终治疗选择。