MITRAL VALVE REGURGITATION INDUCES STRUCTURAL CHANGES

二尖瓣反流引起结构变化

• 批准号: 2910636
• 负责人: RICHARD P COCHRAN
• 金额: $ 31.54万
• 依托单位: UNIVERSITY OF WISCONSIN-MADISON
• 依托单位国家: 美国
• 财政年份: 1997
• 资助国家: 美国
• 起止时间: 1997-07-15 至 2001-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2910636
• 关键词: biomechanics; clinical research; collagen; computer assisted patient care; computer simulation; disease /disorder model; elastin; heart function; histopathology; human subject; immunocytochemistry; light microscopy; mechanical stress; mitral valve; mitral valve insufficiency; morphology; mucopolysaccharides; myocardial ischemia /hypoxia; procollagen; protein biosynthesis; scars; sheep; structural biology; tissue /cell preparation

DESCRIPTION: (Adapted from investigator's abstract) The broad long term objectives of this research are to use a unique 3-D computer model to improve the timing and type of treatment offered to patients with mitral valve regurgitation, and to assess whether there is a role for earlier valve repair in selected etiologies. As the valve is affected by disease, the functional anatomy is often altered, the valve becomes regurgitant, and the normal distribution of mechanical stresses is disrupted. It is the central hypothesis of this application that mitral valve regurgitation, itself, induces structural changes and alters mechanical function. The clinical implication of this hypothesis is that the longer a valve is regurgitant, the more disrupted will be the tissue and the less likely that a surgical repair would be successful. The applicants proposed to test several aspects of this theory and will delineate the mechanisms that contribute to this process, in a three part approach. In Part One, they proposed to assess whether regurgitation induces structural change. Experimental sheep models will be used in which mitral regurgitation is created either by papillary muscle ischemia, or by disruption of the chordae tendineae. After 4, 8, or 16 weeks of regurgitation, the valves will be evaluated for the amount of and the distribution of collagen, as well as changes in elastin and glycosaminoglycans (GAGs). This will answer: 1) Is there an increase in collagen synthesis and/or a change in collagen types in experimentally created mitral regurgitation? 2) Is there a difference in collagen synthesis, collagen types or collagen distribution due to the mechanism of regurgitation? and 3) Is there a concurrent increase in the other structural components of the valve (elastin and glycosaminoglycans (GAGs)) due to regurgitation. In Part Two, the applicants proposed to assess whether the structural change is accompanied by changes in the mechanical properties of mitral valve tissue. The sheep model will be repeated, and in addition human valves will be obtained from explanted hearts from transplant recipients. The biaxial mechanical properties of both will be determined, as well as the collagen orientation to answer: 4) How do the microstructural changes alter the mechanical properties of the valve tissue? 5) Do the pathologic changes seen in human valves parallel either of the experimental models? Finally, in Part Three, the applicants proposed to determine the effect of structural and mechanical property changes on valve function. A three dimensional finite element model will be used which will incorporate the data obtained in Parts One and Two, to answer: (6) Do the microstructural and mechanical property changes significantly alter valve function as tested in a finite element computer model of the mitral valve? 7) Should clinical management of mitral valve disease be altered?

描述：（改编自研究者摘要）广泛的长期 本研究的目标是使用独特的3D计算机模型， 改善二尖瓣患者的治疗时机和类型 瓣膜返流，并评估是否有早期瓣膜作用 修复选定的病因。 由于瓣膜受到疾病的影响， 功能解剖结构经常改变，瓣膜变得不稳定， 机械应力的正常分布被破坏。 是中央 本申请假设二尖瓣反流，本身， 引起结构变化并改变机械功能。 临床 该假设的含义是瓣膜顺应性越长， 组织被破坏的越多， 修复将是成功的。 申请人建议测试几个方面 并将描述有助于这一点的机制 过程中，在三个部分的方法。 在第一部分中，他们建议评估 反流是否引起结构变化。 实验绵羊模型 将用于二尖瓣返流是由乳头状 肌肉缺血或腱索断裂。 在4、8或 返流16周后，将评价瓣膜的 和胶原蛋白的分布，以及弹性蛋白的变化， 糖胺聚糖（GAG）。 这将回答：1）是否有增加 胶原合成和/或胶原类型的变化 造成了二尖瓣返流 2)胶原蛋白有区别吗 合成，胶原类型或胶原分布由于机制， 反胃？ 以及3）是否同时增加了其他 瓣膜的结构成分（弹性蛋白和糖胺聚糖（GAG）） 因为反胃 在第二部分中，申请人建议评估 结构变化是否伴随着机械结构的变化， 二尖瓣组织的性质。 将重复绵羊模型，并在 此外，人类瓣膜将从移植的心脏中获得 受惠人士 将测定两者的双轴机械性能， 以及胶原蛋白的方向来回答：4）如何做， 微结构变化改变了瓣膜组织的机械性能？ 5)人类瓣膜的病理变化是否与 实验模型？ 最后，在第三部分中，申请人建议： 确定结构和机械性能变化对阀门的影响 功能 将使用三维有限元模型， 结合第一部分和第二部分获得的数据，回答：（6）做 显微组织和力学性能的变化显着改变阀 在二尖瓣的有限元计算机模型中测试的功能？ 7)二尖瓣疾病的临床治疗应该改变吗？