MECHANISM & THERAPY OF POST-MI MITRAL REGURGITATION

描述（申请人？s摘要） 近期目标：探讨二尖瓣缺血的机制和治疗 反流（MR），目的是将这些信息应用于临床 问题研究职业发展计划：获得经验和技能， 实验方法和临床研究应用。研究 项目：二尖瓣功能可以根据力平衡来理解 来自乳头肌的束缚力向左平衡的概念 心室闭合力在缺血性MR中，这种力平衡可能会改变， 以损害二尖瓣小叶有效闭合的能力的方式， 环形水平。我们计划进行一个联合的，平行的临床和实验 探讨缺血性二尖瓣返流的发生机制、进展及治疗方法， 所有这些都与缺血性二尖瓣返流是由 二尖瓣与其支持心室的关系异常 结构.这些改变的关系包括不正常的束缚 由于乳头肌移位以及闭合减少而产生的力 由于LV收缩功能障碍而产生的力。具体可测试问题相关 这一假设包括：1）二尖瓣返流的进展， 急性心肌梗死患者与 二尖瓣-心室关系; 2）这些机制也导致 尽管进行了冠状动脉血运重建术，但仍存在持续性MR，从而损害 运动能力和提高肺压力; 3）外部应用 装置和后负荷减少提供了有效的手段， 二尖瓣返流通过使瓣膜和 心室指导奖的目的将通过允许PI 将她的实验专业知识转化为指导临床研究， 缺血性MR的进展和功能结局， 从机制到反映临床情况的模型中的治疗， 患者应用的最终目标。

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.