Anisotropy in Healing Myocardial Scar Tissue

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Following myocardial infarction, the mechanical properties of the healing scar are a critical determinant of left ventricular function, infarct expansion, aneurysm formation and rupture, and ventricular remodeling. Until recently, the only therapeutic options for addressing these consequences were pharmacologic. However, in the past few years, the introduction of a range of options for modifying the cardiac mechanical environment has fundamentally altered our options for clinical postinfarction therapy. The dynamic in vivo cardiac mechanical environment is now just as valid a potential therapeutic target as hormone receptors or signaling cascades. In principle, if mechanical signals that govern scar healing, infarct expansion, aneurysm formation, or ventricular remodeling can be identified, they can be modified. Therefore, one major goal of our work on mechanics of healing infarcts is to provide a better understanding of the evolution of scar structure and mechanics as a platform for designing and appropriately applying therapies to improve ventricular function and to prevent infarct expansion, aneurysm formation, and adverse left ventricular remodeling. Considerable evidence also suggests that the interaction between healing infarcts and the surrounding myocardium works in the other direction: mechanical stimuli applied to the infarct by the myocardium can direct the development of infarct structure and mechanical properties. In particular, our work under the initial funding period of this project (12/01/03 – 11/30/07) revealed a striking correlation between scar structural and mechanical anisotropy in different animal models and the deformation patterns experienced by healing infarcts in those models. We hypothesize that mechanical environment governs the development of anisotropy in healing infarcts and represents a potentially important therapeutic target for directing infarct healing to optimize ventricular function and help prevent long-term adverse remodeling. The work proposed here will test this hypothesis using a combination of unique in vitro model systems and a new innovative approach to manipulating the mechanical environment of healing myocardial infarcts in vivo.