Polymer Therapy for Ischemic Mitral Regurgitation

描述(由申请人提供)： 该项目研究了一种生物相容性和生物惰性生物材料(聚乙烯醇(PVA)聚合物)用于治疗缺血性二尖瓣反流--一种常见的心脏瓣膜疾病，发生在心脏病发作后。我们计划研究这种聚合物的性能的有效性及其对心肌和二尖瓣功能的影响，以便能够以最有效的方式使用于缺血性二尖瓣反流患者。缺血性二尖瓣返流(MR)是心肌梗死的常见并发症，可使晚期死亡率增加一倍。缺血性二尖瓣返流的基本机制是受损的心壁扭曲，这会拉住二尖瓣瓣叶，限制它们关闭的能力。我们建议探索一种治疗缺血性二尖瓣反流的创新方法，使用PVA聚合物，这种聚合物是专门为注射到心肌中而设计的，随后一旦注射就会发生交联。这导致了心肌组织的膨胀和梗塞心肌壁的重新定位，减轻了左心室的变形和变形，从而恢复了二尖瓣功能。我们计划利用已建立的二尖瓣关闭不全的绵羊模型，在聚合物的长期体外测试和体内实验研究的同时，对聚合物材料的应用和开发进行平行的方法。体内动物实验将探讨PVA聚合物注射减少缺血性二尖瓣关闭不全的主要治疗终点。体内实验还将利用血流动力学监测、定量三维超声心动图和声学显微镜研究聚合物注射对心脏跳动的生物力学和生理影响。磁共振弥散成像将评估心肌纤维结构的局部变化。基于体内动物实验的数据和反馈，PVA聚合物的物理和机械特性将以迭代的方式进行优化。同样，来自PVA测试的数据将被共享，以优化体内应用。这种信息共享是该提案并行设计所固有的，它将促进这一多学科团队的合作努力。公共卫生相关性：这项资助研究了一种重要和常见的心脏瓣膜疾病--缺血性二尖瓣反流，对这种疾病的治疗是侵入性的，而且不一致。缺血性二尖瓣反流对公众健康的影响是显著的，因为它影响到心脏病发作后高达20%至30%的患者，以及高达50%的因心肌病而导致的心力衰竭患者。这种瓣膜疾病的存在与预后不良有关，如果存在，死亡率会增加一倍。这笔赠款的目的是探索新的、侵入性更小的疗法来治疗这种重要的瓣膜疾病。

DESCRIPTION (provided by applicant): This project examines the use of a biocompatible and biologically inert biomaterial (polyvinyl alcohol (PVA) polymer) for treatment of ischemic mitral regurgitation-a common valvular disorder which occurs following heart attacks. We plan on studying the effectiveness of properties of this polymer and its effect on the heart muscle and mitral valve function so that it can be used in the most effective way in patients with ischemic mitral regurgitation. Ischemic mitral regurgitation (MR) is a common complication of myocardial infarction that doubles late mortality. The fundamental mechanism underlying ischemic mitral regurgitation is distortion of the damaged heart wall, which pulls on the mitral valve leaflets and restricts their ability to close. We propose to explore an innovative approach toward treating ischemic mitral regurgitation with the use of PVA polymer that has been specifically designed for injection into the myocardium with subsequent crosslinking once injected. This results in myocardial tissue bulking and repositioning of the infarcted myocardial wall with relief of LV distortion and deformation, thereby restoring mitral valve function. We plan a parallel approach of polymer material application and development with long- term in vitro testing of polymer and in vivo experimental studies using an established ovine model of ischemic mitral regurgitation. The in vivo animal experimentation will investigate the main therapeutic endpoint which effectiveness of PVA polymer injection in reducing ischemic mitral regurgitation. The in-vivo experiments will also address the biomechanical and physiological effects of the polymer injection in the beating heart with the use of hemodynamic monitoring, quantitative 3D echocardiography and sonomicrometry. MRI diffusion imaging will assess regional changes, if any, of myocardial fiber architecture. The physical and mechanical characteristics of PVA polymer will be optimized in an iterative fashion, based on data and feedback from the in-vivo animal experiments. Similarly, data from PVA testing will be shared to optimize the in-vivo application. This information sharing, inherent in the parallel design of this proposal, will foster the collaborative efforts of this multidisciplinary team. PUBLIC HEALTH RELEVANCE: This grant examines an important and common cardiac valve disorder, ischemic mitral regurgitation, for which the therapies are invasive and inconsistent. The public health effects of ischemic mitral regurgitation are significant as it affects up to 20 to 30% of patients following a heart attack and up to 50% of patients with heart failure due to a cardiomyopathy. The presence of this valvular disorder is associated with a poor prognosis, doubling mortality when present. The purpose of this grant is to explore novel and less invasive therapies to treat this important valve disorder.