Anisotropic Reinforcement to Improve Post-Infarction LV Function

描述（由申请人提供）：每年有超过一百万的美国人经历心肌梗死（心脏病发作）。心脏病发作后，受损的心肌不能再生；相反，它会在几周内逐渐被疤痕组织所取代。心肌的丧失降低了心脏泵血的能力，在许多情况下，这会引发心脏功能的逐渐下降，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重构，但心脏病发作后发生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脏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，以减少左心室重塑，改善泵功能，或两者兼而有之。最近的计算机模型和实验研究表明，在一个方向上非常坚硬而在其他方向上相对柔软（机械各向异性）的梗塞应该提供最好的心脏功能。这一建议的重点是一种新的方法来创造机械各向异性通过手术强化梗塞。基于初步数据显示各向异性增强可在心脏病发作后立即显著改善泵功能，本项目将在大型动物模型中验证各向异性增强可在心肌梗死后的前2个月内减少左室重构和功能恶化的假设。新的计算模型研究也将确定在不同位置的梗死是否需要不同的机械强化模式来优化左室功能。

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.