SURGERY FOR ACUTE MYOCARDIAL INFARCTION

描述：（改编自申请人摘要） 建议是，心肌的大小，透壁性和位置 梗死，愈合梗死的材料特性和持续的 肾素-血管紧张素-醛固酮系统的刺激决定了 左心室重塑和是否有缺血性二尖瓣返流， 左心室瘤或左心室整体扩张， 发生心室功能的逐渐丧失。 该提案基于 治疗上有吸引力的假设是， 介入治疗可以有利地改变缺血性心脏病后的心室重塑， 左心室衰竭/扩张、二尖瓣返流 和左心室动脉瘤被最小化。 PI具有广泛的 评估心室几何结构、心肌材料特性的经验 和心室力学在大型动物（绵羊）急性 心肌梗死、前尖动脉瘤和急性/慢性缺血性 二尖瓣返流 他有完善的双轴应力拉伸技术 组织样本测试，左心室有限元分析 心肌梗死，左心室和二尖瓣超声测微阵列定位 瓣环几何形状和定量超声心动图 预负荷可复搏功的标准血流动力学测量， 收缩末期弹性 私家侦探会利用他老练的 左心室和二尖瓣力学的多模型分析 一系列旨在加强区域合作的干预措施， 急性梗死（带蒂肌瓣，心外膜Marlex补片，直接 戊二醛注射液），试图治疗性影响 急性梗死区的透壁机械特性。 他将 还扩展了他以前的观察相对于急性和慢性缺血 二尖瓣返流 由于这涉及二尖瓣环 重建这些手术干预可能会影响左 急性梗死后的心室力学。 然后PI将扩展 这种潜在的外科治疗通过操纵肾素-血管紧张素系统 药物治疗缺血心肌， 进行性左心室扩张和功能恶化， 微球诱导的缺血性心肌病模型。

DESCRIPTION: (Adapted from the applicant's abstract) The rationale for this proposal is that the size, transmurality and location of a myocardial infarction, the material properties of the healing infarct and the continued stimulation of the renin-angiotensin-aldosterone system determine how the left ventricle remodels and whether or not ischemic mitral regurgitation, left ventricular aneurysm or global left ventricular dilatation with progressive loss of ventricular function occurs. This proposal is based on the therapeutically attractive hypothesis that medical/surgical interventions can favorably alter ventricular remodeling after an ischemic event such that left ventricular failure/dilatation, mitral regurgitation, and left ventricular aneurysm are minimized. The PI has extensive experience in assessing ventricular geometry, myocardial material properties and ventricular mechanics in large animals (sheep) following acute myocardial infarction, anteroapical aneurysm and acute/ chronic ischemic mitral regurgitation. He has refined techniques of biaxial stress-extension testing of tissue samples, finite element analysis of left ventricular infarction, sonomicrometry array localization of left ventricular and mitral annular geometry, and quantitative echocardiography as related to the standard hemodynamic measurements of preload recruitable stroke work and end-systolic elastance. The PI will build upon his sophisticated multi-model analysis of left ventricular and mitral valvular mechanical status a series of interventions directed toward stiffening the zone of acute infarction (pedicled muscle flap, epicardial marlex mesh, direct glutaraldehyde injection) in an attempt to therapeutically influence the transmural mechanical properties of a zone of acute infarction. He will also extend his previous observations relative to acute and chronic ischemic mitral regurgitation. As this relates to mitral valvular annular reconstruction these surgical interventions are likely to influence left ventricular mechanics following acute infarction. The PI will then extend this potential surgical therapy by manipulating the renin-angiotensin system to pharmaceoutically stiffen ischemic myocardium in order to influence progressive left ventricular dilatation and functional deterioration in a microsphere induced model of ischemic cardiomyopathy.