SURGERY FOR ACUTE MYOCARDIAL INFARCTION

描述：(改编自申请者的摘要)理由 建议是心肌的大小，穿透性和位置 梗死灶、正在愈合的梗死灶的材料特性和继续 肾素-血管紧张素-醛固酮系统的刺激决定了 左心室重构和是否发生缺血性二尖瓣反流， 伴左室壁瘤或左室全心扩大 发生心脏功能的进行性丧失。这项建议是基于 治疗上有吸引力的假说是内科/外科 干预可以有利地改变缺血后的心室重构 左心衰竭/扩张，二尖瓣关闭不全， 和左室壁瘤被降至最低。PI具有广泛的 评估心室几何形状、心肌材料特性的经验 和大型动物(绵羊)急性心肌梗死后的心室力学 心肌梗死、前心尖部动脉瘤和急/慢性缺血 二尖瓣返流。他有精湛的双向拉伸技术。 组织样本的测试，左心室的有限元分析 心肌梗死，左心室和二尖瓣声学显微阵列定位 环状结构和定量超声心动图与 标准血流动力学测量预负荷可招募的卒中工作和 收缩末期弹性。私家侦探将在他老练的基础上 左、二尖瓣机械性能的多模型分析 一系列干预措施，旨在加强 急性心肌梗死(带蒂肌瓣，心外膜肌筋膜网，直接 戊二醛注射剂)，试图在治疗上影响 急性梗死区的透壁力学特性。他会的 我还扩展了他之前关于急性和慢性缺血的观察 二尖瓣返流。因为这与二尖瓣环有关 重建这些外科手术很可能会影响左翼 急性脑梗塞后的室壁力学。然后，PI将扩展 通过操纵肾素-血管紧张素系统进行这种潜在的外科治疗 对缺血心肌进行药理强直，以影响 进行性左心室扩大和功能恶化 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.