MECHANISM & THERAPY OF POST-MI MITRAL REGURGITATION

描述(申请人--S摘要) 近期目标：研究二尖瓣缺血症的机制和治疗 反流(MR)，目标是将这些信息应用于临床 学习。职业发展计划：在以下领域获得经验和技能 实验方法及其在临床研究中的应用。研究 项目：二尖瓣功能可以从力平衡的角度来理解 乳头肌的牵引力平衡左侧的概念 脑室关闭的力量。在缺血型MR中，这种力平衡可能会改变 以损害二尖瓣叶有效闭合的方式 环形水平线。我们计划将临床和实验结合起来，平行进行 评价缺血性MR的机制、进展和治疗的途径 所有这些都与中心假设有关，即缺血性MR是由 二尖瓣与其支持室的异常关系 结构。这些改变的关系包括两个不正常的拴系 乳头肌移位所产生的力以及闭合程度的降低 由于左心室收缩功能障碍而产生的作用力。相关的特定可测试问题 这一假说包括：1)二尖瓣关闭不全的进展 急性心肌梗死患者与心脏功能异常有关 二尖瓣-心室关系；2)这些机制也可导致 尽管接受了冠状动脉血运重建术，但仍坚持MR，从而损害 运动能力和升高肺压力；3)两者外用 装置和后负荷减少提供了减少缺血的有效手段 二尖瓣关闭不全与二尖瓣关闭不全的关系 脑室。导师奖的目标将通过允许PI 将她的实验专业知识用于指导临床研究 缺血性MR的进展和功能转归，并进行过渡 在反映临床情况的模型中从机制到治疗， 患者应用程序的最终目标。

DESCRIPTION (Applicant?s Abstract) Immediate Goals: To examine the mechanism and therapy of ischemic mitral regurgitation (MR) with the goal of applying this information to clinical studies. Career Development Plan: To obtain experience and skills in experimental methodology and application to clinical studies. Research Project: Mitral valve function can be understood in terms of the force-balance concept in which tethering forces from the papillary muscles balance left ventricle closing forces. In ischemic MR, this force-balance may be altered in ways that impair the ability of the mitral leaflets to close effectively at the annular level. We plan a combined, parallel clinical and experimental approach to evaluate the mechanism, progression and therapy of ischemic MR, all relating to the central hypothesis that ischemic MR is caused by an abnormal relationship of the mitral valve to its supporting ventricular structures. These altered relationships involve both abnormal tethering forces due to displacement of the papillary muscles as well as reduced closing forces due to LV contractile dysfunction. Specific testable questions related to this hypothesis include: 1) the progression of mitral regurgitation in patients with acute myocardial infarction relates to abnormalities in the mitral valve-ventricular relationship; 2) These mechanisms also cause persistent MR despite coronary revascularization surgery, thereby impairing exercise capacity and raising pulmonary pressures; 3) both externally applied devices and afterload reduction provide effective means of reducing ischemic mitral regurgitation by normalizing these relationships between the valve and the ventricle. The aims of the mentored award will be met by allowing the PI to translate her experimental expertise to direct clinical studies of progression and functional outcome of ischemic MR, and to make the transition from mechanism to therapy in models reflecting the clinical situation, with the ultimate goal of patient applications.