Alteration in the mitral valve stress and mitral valve interstitial cell deformat

二尖瓣应力的改变和二尖瓣间质细胞变形

• 批准号: 8202466
• 负责人: Rouzbeh Amini
• 金额: $ 4.84万
• 依托单位: UNIVERSITY OF PITTSBURGH AT PITTSBURGH
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-09-01 至 2014-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8202466
• 关键词: Affect; Anticoagulants; Architecture; Cardiomyopathies; Case Study; Cells; Collagen; Computer Simulation; Data; Disease; Effectiveness; Elements; Endocarditis; Etiology; Excision; Extracellular Matrix; Failure; Fiber; Goals; Heart Valves; Hemorrhage; Homeostasis; Image; Laboratories; Longitudinal Studies; Maps; Measurement; Mechanics; Methods; Mitral Valve; Mitral Valve Insufficiency; Modeling; Motion; Operative Surgical Procedures; Organ; Patients; Procedures; Prosthesis; Research; Scientist; Stress; Structural Models; Structure; Surgical sutures; Tachycardia; Techniques; Testing; Thromboembolism; Time; Tissues; United States; Ventricular; base; improved; in vivo; interstitial; interstitial cell; light scattering; mitral valve replacement; multi-photon; novel; programs; repaired; response; simulation; soft tissue

DESCRIPTION (provided by applicant): Many patients in the United States undergo mitral valve (MV) repair each year. Long-term studies have shown less optimistic results for repair durability. This brings into question the effectiveness of such surgical practice and suggesting that MV repair techniques can be improved upon. In most cases, failures were a result of disruption at the leaflet, chordae, or annular suture lines. These failure modes suggest excessive tissue stress and the resulting tissue damage as an etiologic factor. A fundamental aspect underling all types of MV repair is the relation between leaflet geometry, structure, and local tissue stress/homeostasis. Altered MV stress, caused by disorders such as tachycardia-induced cardiomyopathy, mitral regurgitation, and abnormal ventricular wall motion has been shown to induce significant changes in mitral valve interstitial cell (MVIC) activities and MV extracellular matrix (ECM) collagen content. Similarly, by changing the mechanical loading on the leaflet tissue, MV repairs may alter the MVIC deformation, ECM collagen content, and tissue homeostasis, and subsequently could limit durability of the repair. Therefore, understanding the repair-induced changes in the tissue stress and microstructure is quintessential in investigating the MV cellular activities and ultimately etiology of MV repair failure. Finite-element (FE) modeling has been employed to estimate native MV leaflet stress. Although important as first steps, these studies have not captured the complexity of MV geometry, microstructure, and mechanobiological responses to altered loading. Our long-term goal of the research program is elucidating the etiology of MV repair failure and studying how changes in leaflet tissue stress affect MVIC biosynthetic abilities, and how these changes in-turn affect MV repair durability. In the current project, we emphasize the repair-induced MV stress alteration and the changes in the microstructure of the MV tissues using a novel FE model. This model will allow us to directly connect MVIC deformation to altered loading during MV repair. We hypothesize that: MV mechanical loading controls tissue homeostasis and ECM remodeling (via MVICs), with deleterious repair-induced altered loading leading to microstructural changes that affect long-term repair durability. We propose the following specific aims: Specific Aim 1. Develop an anatomically faithful micro/meso-scale quasi-static 3D FE model of MV apparatus to quantify stress and deformation at cellular, tissue, and organ levels. Specific Aim 2 Assess the validity of FE model predictions by comparing the simulation results to in- vivo experimental data. Specific Aim 3 Investigate changes in regional tissue stress, microstructure, and MVIC deformation following repair. PUBLIC HEALTH RELEVANCE: Although mitral valve repair surgeries are commonly performed, their long-term durability has not been completely satisfying. The purpose of this study is to use experimental measurements and computer modeling to evaluate the altered mechanical loading and deformation to which mitral valve cells are subjected following repair surgeries. This study will improve understanding of repaired-induced mitral valve microstructural changes, which will greatly aid clinicians and scientists in repairing or replacing this tissue.

描述（由申请人提供）：在美国，每年有许多患者接受二尖瓣（MV）修复。长期研究显示，修复耐久性的结果不太乐观。这引起了对这种手术实践的有效性的质疑，并建议可以改进中压修复技术。在大多数情况下，失败是由于小叶、索或环状缝合线的破坏。这些失效模式表明过度的组织应力和由此导致的组织损伤是一个病因。所有类型的中压修复的一个基本方面是小叶几何、结构和局部组织应力/稳态之间的关系。由心动过速引起的心肌病、二尖瓣反流和心室壁运动异常等疾病引起的中压应激改变已被证明可引起二尖瓣间质细胞（MVIC）活性和中压细胞外基质（ECM）胶原含量的显著变化。同样，通过改变小叶组织的机械负荷，MV修复可能会改变MVIC变形、ECM胶原含量和组织稳态，从而限制修复的耐久性。因此，了解修复引起的组织应力和微观结构的变化是研究中压细胞活动和中压修复失败的最终病因的关键。采用有限元模型对原始MV叶面应力进行了估计。尽管这些研究是重要的第一步，但它们并没有捕捉到MV几何结构、微观结构和对改变载荷的力学生物学反应的复杂性。我们的长期研究目标是阐明中压修复失败的病因，研究小叶组织应激的变化如何影响中压生物合成能力，以及这些变化如何反过来影响中压修复的持久性。在本项目中，我们使用一种新的有限元模型来强调修复引起的中压应力变化和中压组织的微观结构变化。该模型将使我们能够直接将MVIC变形与MV修复期间改变的载荷联系起来。我们假设：MV机械负荷控制组织稳态和ECM重塑（通过mvic），有害修复诱导的负荷改变导致微观结构变化，影响长期修复耐久性。我们提出以下具体目标：建立一个解剖学上忠实的微/中观准静态三维有限元模型，以量化细胞、组织和器官水平的应力和变形。通过比较模拟结果和体内实验数据，评估FE模型预测的有效性。研究修复后区域组织应力、微观结构和MVIC变形的变化。