Anisotropic Reinforcement to Improve Post-Infarction LV Function

每年有超过一百万的美国人经历心肌梗塞（心脏病发作）。跟随一颗心 一旦心脏病发作，受损的心肌不能再生;相反，它会逐渐被疤痕组织所取代。 几个星期的过程。心肌的丧失降低了心脏泵血的能力， 在许多情况下，这会引发心脏功能的逐渐下降和心脏大小的改变， 重塑（remodeling），最终导致心力衰竭。虽然血管紧张素转换酶 血管紧张素转换酶（ACE）抑制剂可以帮助减少梗死后重塑， 心脏病发作后存活率仍然很高。因为疤痕组织的机械特性 心脏病发作后的形式是心脏功能和最终过渡到心脏病的关键决定因素。 心力衰竭，几种正在开发的新疗法试图改变心脏的机械性能， 该疤痕是为了减少左心室（LV）重构、改善泵功能或两者。最近 计算机模拟和实验研究表明，在一个方向上非常僵硬的梗塞， 在其他方面相对柔软（机械各向异性）应提供最佳的心脏功能。这项建议 重点介绍了一种新的方法，通过外科手术加强梗死，以创造机械各向异性。基于 初步数据显示，各向异性增强显著改善泵功能 心脏病发作后，该项目将测试假设，各向异性强化 减少心肌梗死后前2个月的LV重塑和功能恶化 在大型动物模型中的梗塞。新的计算模型研究也将确定 不同部位的梗死需要不同的机械强化模式以优化LV 功能

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.