The effect of systemic hypertension on prognosis of myocardial infarction: Understanding, prediction and therapy evaluation

全身性高血压对心肌梗死预后的影响：理解、预测和治疗评估

• 批准号: 10091577
• 负责人: Reza Avazmohammadi
• 金额: $ 24.9万
• 依托单位: TEXAS ENGINEERING EXPERIMENT STATION
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-04-15 至 2023-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10091577
• 关键词: 3-Dimensional; Address; Affect; Animal Model; Architecture; Area; Biomechanics; Cardiac; Cardiac Myocytes; Cicatrix; Clinical Research; Collagen Fiber; Complex; Computer Models; Computer Simulation; Data; Death Rate; Development; Diagnosis; Dilatation - action; Elements; Event; Exhibits; Fiber; Foundations; Geometry; Goals; Growth; Heart; Heart failure; Hypertrophy; Image; Imaging Techniques; Infarction; Injections; Intervention; Laws; Left Ventricular Remodeling; Left ventricular structure; Magnetic Resonance Imaging; Maps; Measurement; Measures; Mechanical Stress; Mechanics; Modeling; Muscle Cells; Myocardial; Myocardial Infarction; Myocardium; Natural regeneration; Organ; Pathologic; Patients; Performance; Play; Positioning Attribute; Process; Production; Rattus; Regenerative Medicine; Research; Right ventricular structure; Risk Factors; Role; Site; Solid; Stress; Structure; Study models; Systemic hypertension; Techniques; Testing; Therapy Evaluation; Thinness; Three-Dimensional Imaging; Time; Tissues; Ventricular Remodeling; base; cardiogenesis; computerized tools; functional loss; heart function; hemodynamics; high risk; improved; in vivo; in vivo imaging; insight; normotensive; novel; outcome forecast; paracrine; personalized management; preservation; pressure; response; restoration; simulation; stem cell therapy; stem cells; success; tissue stress; tool

Project Summary Thinning of the heart wall and remodeling of the heart left ventricle (LV) are key consequences of myocardial infarction (MI). These consequences can be considerably influenced by pressure overload in the LV as both a risk factor for MI and a cause of pathological myocardial hypertrophy. The effect of antecedent systemic hypertension (ASH) on the LV remodeling due to MI, and more importantly on the success of regenerative medicine therapies following MI remains poorly understood. Our long-term objective for this proposal is to improve our understanding on how the LV adapts to MI under ASH, and to develop an experimentally-validated computational model that can predict this adaptation. Traditional measures such as LV dilation and infarct size used to characterize the LV remodeling provide limited information on cardiac performance. New computational tools are needed to reveal detailed description and prognosis of multiscale remodeling of infarcted LV. Following the hypothesis that the LV wall stress regulates the onset and extent of LV remodeling, we will develop an image-based computational model bridging the gap between local microstructural and mechanical adaptations of LV myocardium and organ-level functional changes. We will then extend this model to simulate and predict possible improvements in the contractility of infarcted myocardium under ASH following stem-cell interventions. This model provides a platform to investigate the role of wall stress restoration in the improvement of myocardial contractility in infarcted hearts with and without ASH. Towards our goal, we propose to determine the regional hypertrophy and remodeling mechanisms from image- based microstructural and mechanical data obtained from normotensive and hypertensive rat models of MI (Aim 1). We will then build a microstructurally-faithful, rat-specific finite element model that accounts for local growth and remodeling and validate it using in vivo data from the rat models of MI (Aim 2). Finally, we will use our computational model to investigate the correlation between the restoration of the wall stress and the success of stem-cell interventions in our rat models of MI (Aim 3). Three specific aims of this proposal are then summarized as: 1. Quantify the time-course heterogeneous hypertrophy and remodeling events at fiber-, tissue-, and organ-levels following MI under ASH. 2. Develop a time-evolving rat-specific computational model of heart and validate the model using in vivo data. 3. Investigate the correlation between wall stress restoration and the efficacy of stem-cell therapy following MI.

项目摘要 心脏壁的变薄和心脏左心室（LV）的重塑是心肌缺血的关键后果。 心肌梗死（MI）。这些结果可能受到LV中压力过载的显著影响， MI的危险因素和病理性心肌肥大的原因。先行系统效应 高血压（ASH）对MI所致LV重构的影响，更重要的是对再生心肌的成功 心肌梗死后的药物治疗仍然知之甚少。我们这项建议的长远目标是 提高我们对LV如何适应ASH下MI的理解，并开发实验验证的 可以预测这种适应的计算模型。传统的测量方法，如左心室扩张和梗死面积 用于表征LV重构的方法提供的心脏性能信息有限。新 需要计算工具来揭示多尺度重塑的详细描述和预后。 左心室梗死根据左室壁应力调节左室重构的发生和程度的假设， 我们将开发一种基于图像的计算模型，弥合局部微观结构与 LV心肌的机械适应和器官水平的功能变化。然后我们将扩展这个模型 模拟和预测梗死心肌收缩性在ASH下的可能改善， 干细胞干预。该模型提供了一个平台，以研究壁应力恢复的作用， 改善有和无ASH的梗死心脏的心肌收缩力。 为了实现我们的目标，我们建议从图像上确定区域肥大和重塑机制- 基于从正常血压和高血压大鼠MI模型获得的显微结构和力学数据， (Aim 1）。然后，我们将建立一个微观结构的忠实，大鼠特定的有限元模型，占当地 生长和重塑，并使用来自MI大鼠模型的体内数据对其进行验证（目的2）。最后，我们将使用 我们的计算模型，以调查之间的相关性恢复的壁应力和 在我们的MI大鼠模型中干细胞干预的成功（目标3）。本提案的三个具体目标是 总结如下： 1.量化纤维、组织和组织中的时程异质性肥大和重塑事件， 在ASH下MI后的器官水平。 2.开发一个随时间变化的大鼠特定心脏计算模型，并使用 体内数据。 3.研究室壁应力恢复与干细胞治疗疗效之间的相关性 继MI。