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Myocardial Structure, Function, and Remodeling in Mitral Regurgitation

二尖瓣反流中的心肌结构、功能和重塑

基本信息

批准号：
7880934
负责人：
Daniel B Ennis
金额：
$ 24.9万
依托单位：
UNIVERSITY OF CALIFORNIA LOS ANGELES
依托单位国家：
美国
项目类别：
财政年份：
2008
资助国家：
美国
起止时间：
2008-09-25 至 2012-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7880934
关键词：
Accounting Activities of Daily Living Address Affect Anatomy Animal Model Area Caliber Cardiac Cardiac Surgery procedures Chronic Clinical Collaborations Computational Technique Congestive Heart Failure DNA Sequence Rearrangement Data Depressed mood Development Diffusion Disease Elements Endocardium Environment Epicardium Evolution Excess Mortality Faculty Fiber Functional disorder Goals Health Care Costs Heart Heart failure Heterogeneity Histologic Histology Hypertrophy Image Implant Inhibition of Matrix Metalloproteinases Pathway Innovative Therapy Intervention Left Left ventricular structure Length Life Life Expectancy Location Magnetic Resonance Imaging Measures Mechanics Mentors Methods Mitral Valve Insufficiency Modeling Morbidity - disease rate Muscle Muscle Cells Myocardial Needles Operative Surgical Procedures Outcome Pathogenesis Pathology Patients Pattern Phase Physiology Positioning Attribute Process Radial Radiology Specialty Relative (related person)Reproducibility Research Research Infrastructure Research Proposals Rest Rodent Rodent Model Sarcomeres Secure Seeds Shapes Structure Subgroup Surgeon Symptoms System Techniques Testing Thick Time Tissues Torsion Universities Variant Ventricular Ventricular Function Ventricular Remodeling Work Workload base career high risk improved kinematics novel therapeutics response tool

项目摘要

The clinical consequence of severe, uncorrected mitral regurgitation (MR) is excess mortality and morbidity. The timing of surgical intervention in chronic MR remains one of the most challenging clinical decisions in cardiac surgery. A refinement in our understanding of the pathogenesis of ventricular remodeling in mitral regurgitation is clearly needed to improve clinical outcomes. The canonical model of ventricular remodeling in volume overload hypertrophy does not account for transmural differences in hypertrophic remodeling. We now have exciting preliminary results that demonstrate a transmural gradient in ventricular wall remodeling wherein the epicardium thins by 30% and the endocardium thickens by nearly 10% during chronic MR. The overall hypothesis of the work is that transmural differences in the hypertrophic response to chronic mitral regurgitation may portend a poor clinical outcome. My immediate career goal is to develop the necessary experimental, computational, and theoretical tools to test hypotheses about transmural differences in cardiac structure, function, and remodeling in mitral regurgitation. A unique research environment is available to me through an inter-disciplinary collaboration between the Departments of Cardiothoracic Surgery and Radiology at Stanford University. This opportunity affords the ability to gain a deep understanding of cardiac pathophysiology research in addition to further developing my expertise in cardiac magnetic resonance imaging. My career plan includes gaining considerable expertise in experimental cardiac physiology research, quantitative histologic methods, diffusion tensor magnetic resonance imaging (DTMRI), and computational techniques for integrating structure and function data. My long-term career goal is to secure a tenure-track faculty position so that I can continue to answer questions about cardiac structure, function, and remodeling in disease. Work during the Independent Phase will develop the first finite element model of integrated cardiac structure and function from a rodent model of mitral regurgitation using data acquired from MRI tissue displacement and DTMRI. The relevance of this research proposal regards improving our understanding of mitral regurgitation, a common cause of heart failure. The results of this research may help elucidate important changes that underlie the progression from chronic mitral regurgitation to over heart failure and may spur the development of innovative therapies to aid in the treatment of this disease.

严重的，未经纠正的二尖瓣反流（MR）的临床后果是高死亡率和发病率。