Surgery to Prevent Postinfarction Ventricular Remodeling

描述(逐字摘自申请者摘要)：最常见的原因 慢性充血性心力衰竭与心脏重构有关 心肌梗死。这种重构过程可能导致二尖瓣缺血。 反流(MR)、缺血性心肌病和/或左心室(LV) 动脉瘤的形成。这项由一位新的年轻调查员提出的建议的重点是 来检验这样的假设：局部墙应力的增加和局部墙体的变化 梗死区的材料特性驱动着重塑过程。 第一个具体目标是确定二尖瓣几何形状和 3例患者在心室重塑后发生边界区扩张 不同的梗塞绵羊模型。第二个具体目标是评估 可预防心力衰竭的不同干预措施 是心脏重塑的结果。第三个具体目标是评估 驱动心脏和二尖瓣病变的物理机制(S) 由于重塑过程而产生的应力分布。 关于具体目标1，国际和平倡议建议利用高分辨率 声学显微阵列定位技术(SAL)测量二尖瓣病变 重建过程中产生的环状和瓣膜下几何形状。这个 PI将测量梗塞的大小和位置、交界区、 在三种不同的慢性绵羊梗死中随着时间的推移和远隔心肌的变化 模特们。连续的微球注射将用于精确测量 局部收缩能力和血流量。定量彩色血流多普勒 超声心动图将用于评估二尖瓣的程度。 反流和左心室扩张。光镜组织切片 将从梗死区、交界区和远隔心肌获得显微镜。 以预定的间隔评估类型III的相对浓度 和I型胶原蛋白。拟研究的三种绵羊模型包括：1)结扎 第一条和第二条钝性边缘血管形成梗塞 包括24%的左心室重量和中度左 无心力衰竭或二尖瓣缺血迹象的脑室扩张 反流，2)结扎第一和第二对角支 左冠状动脉前降支，导致急性心肌梗塞 大约24%的左心室重量会导致 左心室进行性扩张和心力衰竭，以及3)结扎 冠状动脉回旋支的第二和第三钝缘动脉 动脉形成急性梗塞，占左动脉的21% 导致心力衰竭和进行性严重的心室包块 8-12周的缺血性二尖瓣反流。 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心衰的疗效观察 改建。包括：1)发病后1小时和6小时的再灌流 2)缺血后6小时再灌流； 环状成形术的实施，以及3)梗死区的机械约束 使用Marlex网状物和明胶-间苯二酚-福尔马林胶。 具体目标3将通过分析从以下方面获得的数据来实现 生成三维二尖瓣的特定目标1和2的研究 使用精确的左心室几何数据进行构建。一种有限元 将采用前期工作部分中介绍的方法进行计算 局部左心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和心力衰竭的发展 一种新的手术程序来预防它。

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.