Surgery to prevent postinfarction ventricular remodeling

手术预防梗死后心室重构

• 批准号: 8447531
• 负责人: Robert C Gorman
• 金额: $ 56.55万
• 依托单位: UNIVERSITY OF PENNSYLVANIA
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-04-01 至 2015-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8447531
• 关键词: Acute myocardial infarction; Affect; Algorithms; American; Animal Model; Apoptosis; Biochemistry; Biocompatible Materials; Biology; Cardiac; Catheters; Cause of Death; Characteristics; Chronic; Clinical; Collagen; Congestive Heart Failure; Control Groups; Coronary Arteriosclerosis; Coronary Occlusions; Data; Devices; Diastolic blood pressure; Dilatation - action; Durapatite; Echocardiography; Elements; Extracellular Matrix; Finite Element Analysis; Funding; Gel; Goals; Health; Heart; Hour; Image; Imaging Techniques; Infarction; Injection of therapeutic agent; Intervention; Left; Left Ventricular Function; Left Ventricular Remodeling; Magnetic Resonance Imaging; Maps; Matrix Metalloproteinases; Measures; Mechanics; Methods; Microspheres; Mitral Valve; Mitral Valve Insufficiency; Modeling; Morphology; Muscle Cells; Myocardial; Myocardial Infarction; Myocardium; Operative Surgical Procedures; Optics; Pathologic; Patients; Perfusion; Prevention; Procedures; Process; Property; Reperfusion Therapy; Risk Factors; Shapes; Sheep; Stress; Stretching; Sturnus vulgaris; Suspension substance; Suspensions; Techniques; Testing; Theoretical model; Therapeutic; Thick; Three-Dimensional Echocardiography; Time; Tissues; Ventricular; Ventricular Remodeling; base; clinical application; clinically relevant; design; improved; innovation; light scattering; novel; novel strategies; prevent; repaired; screening; tool

DESCRIPTION (provided by applicant): Congestive heart failure (CHF) causes the death of 250,000 Americans each year. The majority of cases result from myocardial infarction (MI) induced left ventricular (LV) remodeling. Remodeling is manifest by LV dilatation and global loss of contractile function; significant mitral regurgitation (ischemic mitral regurgitation- IMR) develops in at least 35% of these patients and may exacerbate the phenomenon. The goal of this project is use well characterized and clinically relevant ovine infarction models to elucidate the mechanism of post MI remodeling to an extent that has not been previously possible. We will focus on two common mechanical sequelae of MI: infarct expansion and IMR. In Specific Aim 1, we test the hypothesis that infarct expansion (stretching) drives LV remodeling by increasing stress in the borderzone (BZ) myocardium. Increased BZ stress produces a self-perpetuating phenomenon by decreasing contractile strain in the region and causing inherent changes in myocyte and extracellular matrix biology that allows for propagation of the abnormal stress fields to progressively more remote myocardial regions. We have developed innovative and powerful technical capabilities to quantitatively assess all components of this pathologic cascade. Optical flow mapping of tagged MRI images will be used to measure truly 3D myocardial strains. Myocardial stress distribution will be calculated using state-of-the-art finite element analysis based on the MRI strain data. Infarct material properties will be measured using biaxial mechanical testing. In Specific Aim 1 three therapeutic approaches to limit infarct expansion early after MI will be studied: heart wrapping with the Acorn CSD(R), infarct reperfusion and calcium hydroxyapatite microsphere gel injection. In Specific Aim 2 using the same tools we focus on treating the chronically remodeled heart and test the hypothesis that even small (<4.5%) fractional changes in LV wall volume (caused by calcium hydroxyapatite microsphere gel injection) can significantly improve cardiac mechanics when optimally located. In Specific Aim 3 we focus on the chronically remodeled heart with IMR and test the hypothesis that surgical repair techniques that are designed to increase mitral leaflet curvature (and theoretically reduce leaflet/chordal stress) will be superior to flat ring annuloplasty in improving regional and global LV function in severely remodeled hearts with established IMR. Saddle-shaped annuloplasty and leaflet augmentation will be used to manipulate leaflet curvature. A novel 3D echocardiography based approach to measuring leaflet geometry will be used.

描述（由申请人提供）：充血性心力衰竭（CHF）每年导致25万美国人死亡。大多数病例是由心肌梗塞（MI）引起的左心室（LV）重塑引起的。重塑通过LV扩张和全球收缩功能丧失表现出来；至少35％的患者中会出现明显的二尖瓣反流（缺血性二尖瓣反流 - IMR），并可能加剧这种现象。该项目的目的是使用良好的特征和临床相关的卵巢梗塞模型来阐明MI重塑后的机制，以前尚未实现。我们将重点关注MI：梗塞扩张和IMR的两个常见的机械后遗症。在特定的目标1中，我们检验了以下假设：梗塞扩张（拉伸）通过增加边界区域（BZ）心肌的应力来驱动LV重塑。增加的BZ应力通过减少该区域的收缩菌株并引起心肌和细胞外基质生物学的固有变化而产生自我延续现象，从而使异常应力场传播以逐渐远程心肌区域的传播。我们已经开发了创新和强大的技术能力，以定量评估该病理级联的所有组成部分。标记的MRI图像的光流映射将用于测量真正的3D心肌菌株。心肌应力分布将使用基于MRI应变数据的最新有限元分析来计算。梗塞材料特性将使用双轴机械测试测量。在特定的目标中，将研究MI早期限制梗塞扩张的三种治疗方法：用ACORN CSD（R），梗塞再灌注和羟基磷灰石微球凝胶注射的心脏包裹。在使用相同工具的特定目标2中，我们专注于治疗慢性重塑的心脏，并检验以下假设：即使是小小的（<4.5％）的LV壁体积的分数变化（由羟基磷灰石微球凝胶注射引起）也可以显着改善最佳位置的心脏力学。在特定的目标3中，我们专注于IMR长期重塑的心脏，并测试旨在增加二尖瓣曲面曲率（并且理论上减少小叶/弦胁迫）的手术修复技术将优于平坦环形被告术在改善区域和全球LV功能中，可与已建立的IMR相关的IMR。鞍形的环形成形术和小叶增强将用于操纵小叶曲率。将使用一种基于3D超声心动图的新型方法，用于测量小叶几何形状。