TRANSMURAL DEFORMATION

左侧复杂纤维结构中的肌纤维缩短 脑室被转换成一个有效的协调的脑室 收缩。跨越几十年的研究已经解决了这个问题。 了解局部肌纤维收缩如何导致空洞体积的变化。 直到最近才开发出解决这个问题的定量方法 用来测量三维变形及其方向的 足够的分辨率将局部变形与局部肌纤维联系起来 解剖学。这些研究表明，在左心室游离壁 第一个应变主轴的方向(方向 最大的缩短)几乎不像纤维那样在透壁上变化 方向。这意味着存在实质性的垂直缩短。 在收缩过程中向局部纤维方向移动。在现在，有 在此过程中，垂直于局部纤维方向的长度显著缩短 收缩。在目前的建议中，我们将继续探讨 假设肌细胞的相对肌纤维位置或形状发生变化 或收缩过程中的间质是这些交叉纤维应变的原因。 左心室的正常电活动，起始于 穿过希氏-浦肯野系统，通过 房室结，提供相对同步的激活 心室肌。最新的信息表明， 机械活动与心肌梗死的关系 激活要复杂得多。在目前的提案中，我们计划使用 新开发的表面与激活时间相适应的技术，以及 植入的标记阵列，以确定变形的空间梯度。 容量超负荷时心肌应变的变化 传统上被认为是对 脑室负荷状况。然而，最近的研究表明， 表明这些应变的变化可以直接将信号传递到 代偿性肥厚，以室壁应力终极正常化为 后果。通过调节细胞生长，改变区域 应变最终可能改变并反映局部加载参数。 急性发作的容量超负荷导致双侧肌肉的大幅增加 和心肌的非肌细胞成分。在这项研究中，我们建议 (1)观察穿壁功能变化的时间进程。 心肌肥厚的发生，以及(2)相关的时间进程 收缩和舒张期有限应变随时间的变化 ANF、α-骨骼肌动蛋白、MLC2、 热休克蛋白、纤维连接蛋白和胶原蛋白。我们的方法有几个优点 而不是以前用来检查 心肌功能和肥大。首先，有限变形可能 在任何任意参照系中进行评估。有了当地的知识 肌纤维解剖学这将允许检查变形在 局部纤维方向和交叉纤维方向。这应该是 然后允许更直接地评估局部机械刺激 蛋白质合成增加，机械效应增强 收缩蛋白和胞外蛋白。第二，如 初步结果，植入的标记物将使我们能够识别 跨墙肌肉的体积，并跟踪体积在 肥大的进展。这将允许我们重复测试 跨壁肥厚程度的差异。

Muscle fiber shortening in the complex fiber architecture of the left ventricle is converted into an efficient coordinated ventricular contraction. Studies that span several decades have addressed the problem of how local myofiber contraction contributes to changes in cavity volume. ONly recently have quantitative approaches to this problem been developed which measure three-dimensional deformations and their directions with sufficient resolution to relate local deformation to local myofiber anatomy. These studies have shown that in the left ventricular free wall the orientation of the first principal axis of strain (direction of greatest shortening) does not vary transmurally nearly as much as the fiber direction. This implies that there is substantial shortening perpendicular to the local fiber direction during contraction. In the present there is substantial shortening perpendicular to the local fiber direction during contraction. In the present proposal, we will continue to explore the hypothesis that relative myofiber position or shape changes of the myocyte or interstitium during contraction account for these cross-fiber strains. The normal electrical activation of the left ventricle, initiated from the atrium and traveling through the His-Purkinje system via the atrioventricular node, provides for relatively synchronous activation of ventricular muscle. Most current information indicates that with ventricular activation the relationship between mechanical activity and activation is much more complex. iN the present proposal, we plan to use a newly developed technique for fitting surfaces to activation times, and to arrays of implanted markers to determine spatial gradients of deformation. Changes in myocardial strain in the presence of volume overload have classically been considered a passive response to the abnormalities of ventricular loading conditions. More recent studies, however, have indicated that these changes in strain may directly transduce the signal to compensatory hypertrophy, with ultimate normalization of wall stress as a consequence. Through the regulation of cell growth, changes in regional strain may ultimately alter, as well as reflect, local loading parameters. The acute onset of volume overload induces large increases in both muscle and nonmyocytic constituents of the myocardium. In this study, we propose (1) to examine the time course of the changes in transmural function of the myocardium as hypertrophy occurs, and (2) to correlate the time course of changes in systolic and diastolic finite strains with the time course of increases and decreases in mRNA levels for ANF, alpha-skeletal actin, MLC2, HSP, fibronectin, and collagen. Our approach will have several advantages over those previously used to examine the relationship between changes in function and hypertrophy of cardiac muscle. First, finite deformation may be assessed n any arbitrary reference system. With knowledge of the local myofiber anatomy this will allow the examination of deformation in the direction of local fibers and in the cross-fiber direction. This should then allow a more direct assessment of the local mechanical stimulus to increased protein synthesis, and of the mechanical effects of increased contractile and extracellular protein. Second as discussed in the preliminary results, the implanted markers will allow us to identify small volumes of muscle across the wall and to track changes in volume during the progression of hypertrophy. This will allow us to test repeatedly for transmural differences in the amount of hypertrophy.