Anisotropic Reinforcement to Improve Post-Infarction LV Function

各向异性强化可改善梗塞后左心室功能

基本信息

批准号：
8403788
负责人：
JEFFREY W HOLMES
金额：
$ 17.87万
依托单位：
UNIVERSITY OF VIRGINIA
依托单位国家：
美国
项目类别：
财政年份：
2012
资助国家：
美国
起止时间：
2012-01-01 至 2014-12-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8403788
关键词：
Acute Address Adrenergic beta-Antagonists Affect American Angioplasty Angiotensin-Converting Enzyme Inhibitors Animal Model Animals Anisotropy Anterior Area Canis familiaris Cardiology Cicatrix Clinical Computer Simulation Coronary artery Data Deterioration Development Fibrinolytic Agents Goals Healed Health Heart Heart failure Hour Infarction Lead Left Left Ventricular Function Left Ventricular Remodeling Location Mechanics Mental Depression Methods Muscle Myocardial Infarction Myocardium Natural regeneration Patients Pattern Pharmaceutical Preparations Preparation Property Psychological reinforcement Pump Recurrence Risk Role Shapes Stents Testing Therapeutic Tissues Ventricular Ventricular Function Woman Work base blood pump clinical application experience follow-up healing heart dimension/size heart function improved innovation men novel older patient prevent research study

项目摘要

Over a million Americans experience a myocardial infarction (heart attack) each year. Following a heart attack, damaged heart muscle cannot regenerate; instead, it is gradually replaced by scar tissue over the course of several weeks. The loss of heart muscle reduces the ability of the heart to pump blood, and in many cases this triggers a gradual decline in heart function and alterations in heart size and shape (remodeling) that ultimately lead to heart failure. Although drugs such as angiotensin converting enzyme (ACE) inhibitors can help reduce post-infarction remodeling, the risk of developing heart failure after surviving a heart attack remains high. Because the mechanical properties of the scar tissue that forms after a heart attack are critical determinants of both heart function and the eventual transition to heart failure, several new therapies under development attempt to modify the mechanical properties of that scar in order to reduce left ventricular (LV) remodeling, improve pump function, or both. Recent computer modeling and experimental studies suggest that infarcts that are very stiff in one direction but relatively soft in others (mechanically anisotropic) should provide the best heart function. This proposal focuses on a novel method to create mechanical anisotropy by surgically reinforcing the infarct. Based on preliminary data showing that anisotropic reinforcement dramatically improves pump function immediately after a heart attack, this project will test the hypothesis that anisotropic reinforcement reduces LV remodeling and functional deterioration over the first 2 months folowing myocardial infarction in a large animal model. New computational modeling studies will also determine whether infarcts in different locations require diferent patterns of mechanical reinforcement to optimize LV function.

每年有超过一百万美国人经历心肌梗塞（心脏病发作）。追随一颗心发作时，受损的心肌无法再生；相反，它逐渐被疤痕组织取代持续数周的过程。心肌的损失会降低心脏泵血的能力，在许多情况下，这会引发心脏功能逐渐下降以及心脏大小和形状的改变最终导致心力衰竭的形状（重塑）。虽然血管紧张素转换酶等药物酶（ACE）抑制剂可以帮助减少梗死后重构，即发生心力衰竭的风险心脏病发作后幸存下来仍然很高。因为疤痕组织的机械特性心脏病发作后的形态是心脏功能和最终过渡到心脏功能的关键决定因素心力衰竭，几种正在开发的新疗法试图改变心力衰竭的机械性能去除疤痕是为了减少左心室 (LV) 重塑、改善泵功能，或两者兼而有之。最近的计算机建模和实验研究表明，梗塞在一个方向上非常僵硬，但其他相对较软（机械各向异性）应提供最佳的心脏功能。这个提议专注于一种通过手术强化梗塞来产生机械各向异性的新方法。基于初步数据显示，各向异性加固可显着改善泵功能心脏病发作后，该项目将立即检验各向异性强化的假设减少心肌梗塞后头 2 个月内的左室重塑和功能恶化大型动物模型中的梗塞。新的计算模型研究还将确定是否不同部位的梗塞需要不同的机械强化模式来优化左心室功能。