MECHANICAL REGULATION OF DILATED CARDIOMYOPATHY

描述：扩张型心肌病是一种心脏疾病， 例导致心功能下降，最终导致充血性心脏病 失败机械因素，如应力和应变， 调节因子在心脏肥大等疾病中的作用。整体 该建议的假设是机械因素起重要作用 在扩张型心肌病和心脏病相关的组织重塑中， 失败先进的计算模型结合实验 在具有不同心力衰竭病因的啮齿动物中的研究（遗传和 机械诱导）将有助于阐明机械因素在 心脏扩张和衰竭的进展。以下假设将 （1）扩张型心肌病和最终的心力衰竭是由以下因素介导的： 心脏上的机械负荷，以及从代偿性 从肥厚状态到心力衰竭取决于 应力或应变。心脏功能的研究之前和之后，这个短暂的 相位可以确定哪些机械因素是重要的。(2)的变化 残余应力对心脏的局部功能具有重要影响， 并且可能是心力衰竭中功能障碍的机制。我们将调查 这种可能性通过量化几何形状和组织结构， 心室在从扩张到扩张的过渡期间的无应力状态 故障，并使用数学模型来预测随后的异常变化， 舒张期和收缩期壁应力。(3)我们预计会有变化。区域 在细胞和整体水平上，肌细胞定向是 心脏扩张和衰竭。为了验证这一假设， 和区域变化的层流片取向将被测量期间 过渡到失败。我们会把这些措施纳入 心脏的计算模型，然后独立地改变心肌细胞， 在模型中的方向，并比较功能的结果与那些 通过实验获得的。我们建议，这些区域结构性变化 伴随着舒张性心力衰竭，并且是降低舒张性心力衰竭的机制。 纤维缩短和收缩期间壁收缩的能力。

DESCRIPTION: Dilated cardiomyopathy is a disease of the heart that in most cases leads to decreased cardiac function and eventually to congestive heart failure. Mechanical factors such as stress and strain have been implicated as regulatory factors in diseases such as cardiac hypertrophy. The overall hypothesis of this proposal is that mechanical factors play a significant role in the tissue remodeling associated with dilated cardiomyopathy and cardiac failure. Sophisticated computational models in conjunction with experimental studies in rodents with different etiologies of heart failure (both genetic and surgically-induced) will help elucidate the role of mechanical factors in the progression of cardiac dilation and failure. The following hypotheses will be tested: (1) Dilated cardiomyopathy and eventual heart failure are mediated by mechanical loads on the heart, and the transition from a compensated hypertrophic state to cardiac failure is dependent on a critical level of stress or strain. Studies of cardiac function before and after this transitory phase can determine which mechanical factors are important. (2) A change in residual stress has important consequences for regional function in the heart, and may be a mechanism of dysfunction in heart failure. We will investigate this possibility by quantifying geometry and tissue structure in the stress-free state of the ventricle during the transition from dilation to failure, and use mathematical models to predict subsequent abnormal changes in diastolic and systolic wall stresses. (3) We expect that changes in. regional myocyte orientation, both at the cellular and global levels, are mechanisms of cardiac dilatation and failure. To test this hypothesis, local myocyte disarray and regional variations in laminar sheet orientation will be measured during the transition to failure. We will incorporate these measures into computational models of the heart, and then independently alter the myocyte orientation in the model, and compare the functional results with those obtained experimentally. We propose that these regional structural changes accompanies dilatory heart failure, and are mechanisms behind the reduction in fiber shortening and the ability of the wall to thicken during systole.