Polymer Therapy for Ischemic Mitral Regurgitation

描述（由申请人提供）： 该项目研究了使用生物相容性和生物惰性生物材料（聚乙烯醇（PVA）聚合物）治疗缺血性二尖瓣狭窄-心脏病发作后发生的常见瓣膜疾病。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，以便它可以以最有效的方式用于缺血性二尖瓣返流患者。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心脏壁的变形，这会拉动二尖瓣瓣叶并限制其关闭的能力。我们建议探索一种使用PVA聚合物治疗缺血性二尖瓣返流的创新方法，PVA聚合物专门设计用于注射到心肌中，注射后进行交联。这导致心肌组织膨胀和梗死心肌壁的重新定位，减轻LV扭曲和变形，从而恢复二尖瓣功能。我们计划采用一种平行的方法来应用和开发聚合物材料，并使用已建立的缺血性二尖瓣返流绵羊模型进行聚合物的长期体外测试和体内实验研究。体内动物实验将研究PVA聚合物注射液减少缺血性二尖瓣返流的有效性的主要治疗终点。体内实验还将通过使用血液动力学监测、定量3D超声心动图和声显微测量来解决跳动心脏中聚合物注射的生物力学和生理效应。MRI弥散成像将评估心肌纤维结构的局部变化（如有）。PVA聚合物的物理和机械特性将根据体内动物实验的数据和反馈以迭代方式进行优化。同样，将共享PVA试验数据，以优化体内应用。这一信息共享是本提案平行设计的固有内容，将促进这一多学科小组的协作努力。公共卫生相关性：该基金审查了一种重要而常见的心脏瓣膜疾病，缺血性二尖瓣返流，其治疗方法是侵入性的和不一致的。缺血性二尖瓣返流的公共卫生影响是显著的，因为它影响高达20 - 30%的心脏病发作后患者和高达50%的心肌病心力衰竭患者。这种瓣膜疾病的存在与预后不良相关，当存在时死亡率加倍。这项资助的目的是探索新的和侵入性较小的治疗方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.