Biopolymer injection for treatment of ischemic MR

描述（由申请人提供）：该项目探索了使用新型生物相容性材料（聚乙烯醇）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。我们计划研究这种生物材料的特性及其对心肌和瓣膜功能的影响，以便其能够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。我们已经证明，这个过程可以通过外科手术用折叠术或外部补片重塑心脏来逆转;然而，这些方法覆盖了大部分心脏，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，使用专门设计用于注射到心肌中的生物材料，注射后进行交联。这导致心肌组织膨胀和梗塞心肌壁的重新定位，减轻LV扭曲和变形，从而呈现更正常的形状，减轻二尖瓣小叶上的张力。该方法还具有微创实施的潜力，例如通过经皮递送。为了实现临床问题和开发技术的综合，该提案将汇集几个领域的专业知识：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，开发具有适于缓解心室缺血性变形的物理和机械特性的生物材料（MGH和剑桥聚合物集团公司（查尔斯敦，MA）生物材料实验室的Orhun Muratoglu和Gavin Brathwaite博士），用于评估心肌纤维结构变化的MRI扩散成像：（货车Wedge博士）和心血管生理学和外科学（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).