This proposal seeks to develop new surgical procedures based upon knowledge of changes in left ventricular (LV) mechanics, material properties and geometric shape for acute myocardial infarctions (AMI) of different, specific ventricular locations. The project tests a central hypothesis: that surgical interventions can favorably alter ventricular remodeling or the effects of remodeling after AMI. The project focuses on ischemic mitral regurgitation (MR), antero-apical LV aneurysm and large antero-apical AMI. The proposed work will utilize our well-developed sheep models of antero- apical myocardial infarctions of 22 and 30% of the LV mass; 22% infarctions that produce ischemic MR involving either the anterior or posterior papillary muscle; acute, severe MR after 30% infarctions; and posterior infarctions that do not produce aneurysm or MR. The LV will be imaged using four techniques; sonomicrometry array localization (SAL), quantitative echocardiography, serial ventriculography and cine magnetic resonance imaging. Material properties of infarcted, border zone and remote myocardium will be assessed using our biaxial stress-extension apparatus. Changes in the interrelationships of mitral valve subunits (i.e., annulus, papillary muscle, adjacent ventricular wall) after coronary artery occlusion produces ischemic MR; the components of the valve itself do not change (e.g., leaflets, chordae). We will use SAL to track these changes and devise reparative operations to reverse the changes and restore mitral valvular competence. We will use multiple imaging techniques, biaxial stress-extension studies, and different infarction models to describe the remodeling process after LV infarctions of specific size and location. Our goal is to quantitate regional strains, calculate regional stresses, and to observe how these are redistributed during remodeling. We will assess LV mechanics and correlate these with hemodynamic measurements after plication or patching antero-apical LV aneurysms. We will evaluate both an inert, felt patch and a patch of viable, nonstimulated skeletal muscle. We will attempt to modify the material properties of antero-apical LV infarcts to reduce ventricular deformation and to improve ventricular performance by modifying the material properties of the infarct by reperfusion, an angiotensin converting enzyme inhibitor, and by direct injection of a stiffening material. The heart is a pump. These studies are designed to develop surgical interventions to improve early and long-term ventricular performance after AMI.
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