Acute myocardial ischemia and infraction cause regional alterations in local ventricular function, wall stress, and the passive and active material properties of the myocardium. These changes are associated with regional alterations in coronary perfusion, tissue ultrastructure and cellular contractile dynamics. Regional ventricular mechanics in ischemic and adjacent, normally perfused myocardium are directly related to ischemic injury, coronary perfusion, structural failure, recovery and remodeling. Accurate distributions of ventricular stress and strain are required to understand the interactions between normally perfused and ischemic tissue and the cellular and ultrastructural basis of ischemic dysfunction. The broad objective of the proposed research is to gain a detailed understanding of the regional mechanics and structure of acutely ischemic ventricular myocardium by: (1) determining the distributions of stress, strain and material properties i the ischemic, marginal and normally perfused tissue; and (ii) examining the relationships between these variable and the spatial distributions of myocardial blood flow, extracellular matrix remodeling, and changes in cellular contractile dynamics. A finite element method that accurately models the complex three- dimensional geometry and fiber architecture, the large deformations, and the nonlinear, anisotropic material properties of the ventricular wall will be used to predict myocardial stresses and strains in the passive and active, normal and injured tissue under known loading conditions. To validate the assumptions of the theoretical model and verify the accuracy of its predictions, regional distributions of two- and three- dimensional local deformations will be measured in dog and pig hearts during acute coronary artery occlusions. By altering he model parameters to improve the agreements between theory and experiment, estimates of the passive and active material properties of ischemic myocardium will be obtained. The stress and strain distributions will then be correlated with morphological and cell biological studies of tissue and cell isolated from these preparations to elucidate the structural basis of impaired regional function.
