Surgery to Prevent Postinfarction Ventricular Remodeling

描述（来自申请人摘要的逐字记录）： 慢性充血性心力衰竭与发生在 心肌梗塞这种重塑过程可导致缺血性二尖瓣 反流（MR）、缺血性心肌病和/或左心室（LV） 动脉瘤形成这一建议的重点，由一个新的年轻调查员，是 为了检验局部室壁应力增加和 梗塞边缘区的材料性质驱动重塑过程。 第一个具体目标是确定二尖瓣几何形状的变化， 在三个心室重构后发生的边缘区扩张， 不同的绵羊梗死模型。第二个具体目标旨在评估 不同的干预措施，可以防止发生心力衰竭， 心室重塑的结果。第三个具体目标是评估 驱动心室和二尖瓣变化的物理机制 由于重塑过程而发生的应力分布。 关于具体目标1，PI建议使用高分辨率 超声测微阵列定位技术（SAL）测量二尖瓣变化 瓣环和瓣下几何形状，这是重塑过程的结果。的 PI将测量梗死的大小和位置，边缘区， 在三种不同的慢性绵羊梗死中， 模型连续微球注射将用于精确测量 局部收缩性和血流。定量彩色多普勒 超声心动图将用于评估二尖瓣的程度 反流和左心室扩张。组织切片用于光 将从梗塞区、边缘区和远端心肌获得显微镜检查结果 以评估III型的相对浓度 和I型胶原蛋白。所要研究的三种绵羊模型包括：1）结扎 第一和第二钝缘血管的断裂导致梗死 包括24%的左心室质量和中度左心室质量。 心室扩张，无心力衰竭或缺血性二尖瓣 反流，2）结扎第一和第二对角支， 左前降支冠状动脉，产生急性梗死， 大约24%的左心室质量， 左心室进行性扩张和心力衰竭，以及3）结扎 第二和第三钝缘动脉 动脉产生急性梗死，包括21%的左 心室质量导致心力衰竭和进行性严重 缺血性二尖瓣返流8-12周。 在具体目标2中，将研究三种干预措施，以评估其 预防心肌梗死后左室功能不全的疗效观察 重塑这些包括：1）在发病后1小时和6小时的再灌注， 危险区域的缺血，2）缺血后6小时再灌注， 环成形术的性能，和3）梗死的机械限制 使用Marlex网和明胶-间苯二酚-福尔马林胶。 具体目标3将通过分析从 特定目标1和2中的研究，以生成三维二尖瓣 使用精确的左心室几何数据构建。有限元 将采用预备工作部分中描述的方法计算 局部左室周壁应力分布的变化。 预计这些研究的结果将导致更好的 了解重塑如何导致心力衰竭以及 一种新的外科手术来预防

DESCRIPTION (Verbatim from Applicant's Abstract): The most common causes of chronic congestive heart failure relate to remodeling that occurs after myocardial infarctions. This remodeling process can lead to ischemic mitral regurgitation (MR), ischemic cardiomyopathy, and/or left ventricular (LV) aneurysm formation. The focus of this proposal, by a new young investigator, is to test the hypothesis that increased regional wall stress and changes in the material properties of the infarcted border zone drive the remodeling process. The first Specific Aim is to determine the changes in mitral valve geometry and border zone expansion that occurs after ventricular remodeling in three different infarct sheep models. The second Specific Aim is designed to evaluate different interventions that may prevent the heart failure that occurs as a result of ventricular remodeling. The third Specific Aim is to evaluate the physical mechanism(s) that drive the changes in ventricular and mitral valve stress distribution that occur as a result of the remodeling process. With respect to Specific Aim 1, the PI proposes to utilize high-resolution sonomicrometry array localization technique (SAL) to measure changes in mitral annular and subvalvular geometry that results from the remodeling process. The PI will measure changes in the size and location of the infarct, border zone, and remote myocardium over time in three different chronic sheep infarct models. Serial microsphere injections will be used to precisely measure regional contractility and blood flow. Quantitative color flow Doppler echocardiography will be used to assess the degree of mitral valve regurgitation and left ventricular dilation. Histologic sections for light microscopy will be obtained from the infarct, border zone and remote myocardium at predetermined intervals to assess the relative concentrations of Type III and Type I collagen. The three sheep models to be studied includes: 1) ligation of the first and second obtuse marginal vessels to produce an infarct consisting of 24 percent of the left ventricular mass and moderate left ventricular dilation without evidence of heart failure or ischemic mitral regurgitation, 2) ligation of the first and second diagonal branches of the left anterior descending coronary artery which produces an acute infarction of approximately 24 percent of the left ventricular mass which results in progressive dilation of the left ventricle and heart failure, and 3) ligation of the second and third obtuse marginal arteries of the circumflex coronary artery to produce an acute infarction consisting of 21 percent of the left ventricular mass which results in heart failure and progressively severe ischemic mitral regurgitation over an 8-12 week period. In Specific Aim 2, three interventions will be studied to evaluate their efficacy in preventing heart failure due to post infarction left ventricular remodeling. These include: 1) reperfusion at 1 and 6 hours after the onset of ischemia in the area at risk, 2) reperfusion 6 hours after ischemia and performance of a ring annuloplasty, and 3) mechanical restraint of the infarct using a Marlex mesh and gelatin-resorcinol-formalin glue. Specific Aim 3 will be addressed by analyzing the data obtained from the studies in Specific Aims 1 and 2 to generate a three dimensional mitral construct using precise left ventricular geometric data. A finite element method described in the preliminary work section will be employed to calculate changes in regional left ventricular circumferential wall stress distribution. It is anticipated that the results of these studies will lead to a better understanding of how remodeling results in heart failure and the development of a new surgical procedure to prevent it.