Abstract
BACKGROUND: Adverse remodeling of the left ventricle (LV) following myocardial infarction (MI) leads to heart failure. Recent studies have shown that scar anisotropy is a determinant of cardiac function post-MI, however it remains unclear how changes in extracellular matrix (ECM) organization and structure contribute to changes in LV function. The objective of this study is to develop a model to identify potential mechanisms by which collagen structure and organization affect LV function post-MI. METHODS: A four-region, multi-scale, cylindrical model of the post-MI LV was developed. The mechanical properties of the infarct region are governed by a constitutive equation based on the uncrimping of collagen fibers. The parameters of this constitutive equation include collagen orientation, angular dispersion, fiber stiffness, crimp angle, and density. Parametric variation of these parameters was used to elucidate the relationship between collagen properties and LV function. RESULTS: The mathematical model of the LV revealed several factors that influenced cardiac function post-MI. LV function was maximized when collagen fibers were aligned longitudinally. Increased collagen density was also found to improve stroke volume for longitudinal alignments while increased fiber stiffness decreased stroke volume for circumferential alignments. CONCLUSIONS: The results suggest that cardiac function post-MI is best preserved through increased circumferential compliance. Further, this study identifies several collagen fiber-level mechanisms that could potentially regulate both infarct level and organ level mechanics. Improved understanding of the multi-scale relationships between the ECM and LV function will be beneficial in the design of new diagnostic and therapeutic technologies.