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ACE Inhibition and Cardiac Allograft Vasculopathy

ACE 抑制和心脏同种异体移植血管病

基本信息

批准号：
7810547
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
项目类别：
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/7810547
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 blood supply Vascular remodeling base heart allograft high risk improved improved functioning interstitial mortality pilot trial placebo controlled study pressure prevent prospective public health relevance randomized trial vascular inflammation

项目摘要

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）：