Anisotropic Reinforcement to Improve Post-Infarction LV Function

描述(申请人提供)：每年有超过一百万的美国人经历过心肌梗死(心脏病发作)。心脏病发作后，受损的心肌不能再生；取而代之的是，在几周的时间里，它逐渐被疤痕组织取代。心肌的丧失降低了心脏泵血的能力，在许多情况下，这会触发心脏功能的逐渐下降以及心脏大小和形状的改变(重塑)，最终导致心力衰竭。尽管血管紧张素转换酶(ACE)抑制剂等药物可以帮助减少梗死后的重塑，但在心脏病发作后存活下来后发展为心力衰竭的风险仍然很高。由于心脏病发作后形成的疤痕组织的机械特性是心功能和最终过渡到心力衰竭的关键决定因素，因此正在开发的几种新疗法试图改变疤痕的机械特性，以减少左心室(LV)重塑，或改善泵功能，或两者兼而有之。最近的计算机模拟和实验研究表明，一个方向非常坚硬但其他方向相对较软的梗塞(机械各向异性)应该能提供最佳的心脏功能。这项建议侧重于一种新的方法，通过外科手术强化梗死区来创造机械各向异性。基于初步数据显示，各向异性强化可显著改善心脏病发作后立即的泵功能，该项目将在一个大型动物模型中测试各向异性强化可减少心肌梗死后前2个月的左室重构和功能恶化的假设。新的计算模型研究也将确定不同位置的梗塞是否需要不同的机械强化模式来优化左心功能。 与公共健康相关：每年有100多万美国人经历心肌梗死(心脏病发作)。许多患者在心脏病发作后存活下来，心脏功能逐渐下降，心脏大小和形状发生变化(重塑)，最终导致心力衰竭。这项工作的目标是测试一种创新的新疗法的能力，这种疗法可以在心脏病发作后早期改善心功能，以减少随后的功能恶化和重塑。

DESCRIPTION (provided by applicant): 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 following myocardial infarction in a large animal model. New computational modeling studies will also determine whether infarcts in different locations require different patterns of mechanical reinforcement to optimize LV function. PUBLIC HEALTH RELEVANCE: Over a million Americans experience a myocardial infarction (heart attack) each year. After surviving a heart attack, many patients experience a gradual decline in heart function and alterations in heart size and shape (remodeling) that ultimately lead to heart failure. The goal of this work is to test the ability of an innovative new therapy that improves heart function early after a heart attack to reduce subsequent functional deterioration and remodeling.