Biopolymer injection for treatment of ischemic MR

描述(申请人提供)：该项目探索使用一种新的生物兼容材料(聚乙烯醇)来治疗缺血性二尖瓣反流--一种心脏病发作后常见的瓣膜紊乱。我们计划研究这种生物材料的特性及其对心肌和瓣膜功能的影响，以使其能够以最有效的方式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。我们已经证明，这一过程可以通过使用折叠术或外部补片通过外科手术重塑心脏来逆转；然而，这些方法会使心脏的很大一部分固定，需要心内直视手术。我们建议探索一种创新的方法来实现这一目标，使用生物材料，这些材料是专门为注射到心肌中而设计的，随后在注射后进行交联。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，从而呈现出更正常的形状，缓解了二尖瓣叶上的张力。这种方法也有可能实现微创实施，例如通过经皮递送。为了实现这一临床问题和开发技术的综合，这项建议将汇集多个领域的专业知识：通过三维超声心动图对动物模型中的二尖瓣进行定量分析，开发具有物理和机械特性的生物材料，以缓解缺血室扭曲(麻省理工学院生物材料实验室的Orhun Muratoglu和Gavin Brathwaite博士)，以及用于评估心肌纤维结构变化的磁共振扩散成像(Van Wedeen博士)和心血管生理学和外科(Vlahakes博士)。

DESCRIPTION (provided by applicant): This project explores the use of a novel biocompatible material (polyvinyl alcohol) for treatment of ischemic mitral regurgitation-a common valvular disorder which occurs following heart attacks. We plan on studying the properties of this biomaterial and its effect on the heart muscle and valvular 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 have shown that this process can be reversed by re-shaping the heart surgically with plication or with an external patch; these approaches, however, immobilize a large portion of the heart and require open-heart surgery. We propose to explore an innovative approach toward achieving this goal with the use of biomaterials that are 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 assuming a more normal shape that relieves the tension on the mitral leaflets. This approach also has the potential for minimally invasive implementation such as through percutaneous delivery. To achieve this synthesis of clinical problem and developmental techniques, this proposal will bring together expertise in several areas: quantitative analysis of the mitral valve in animal models by three-dimensional echocardiography, development of a biomaterial with physical and mechanical properties adapted to relieve ischemic distortion of the ventricle (Drs. Orhun Muratoglu and Gavin Brathwaite of Biomaterials Laboratory at MGH and Cambridge Polymer Group, Inc, Charlestown, MA), MRI diffusion imaging for assessment of changes in myocardial fiber architecture :(Dr. Van Wedeen) and cardiovascular physiology and surgery (Dr. Vlahakes).