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.
Showing the most recent 10 out of 36 publications
