Abstract
Cardiac aging is characterized by diastolic dysfunction of the left ventricle (LV), which is due in part to increased LV wall stiffness. In the diastolic phase, myocytes are relaxed and extracellular matrix (ECM) is a critical determinant to the changes of LV wall stiffness. To evaluate the effects of ECM composition on cardiac aging, we developed a mathematical model to predict LV dimension and wall stiffness changes in aging mice by integrating mechanical laws and our experimental results. We measured LV dimension, wall thickness, LV mass, and collagen content for wild type (WT) C57/BL6J mice of ages ranging from 7.3 months to those of 34.0 months. The model was established using the thick wall theory and stretch-induced tissue growth to an isotropic and homogeneous elastic composite with mixed constituents. The initial conditions of the simulation were set based on the data from the young mice. Matlab simulations of this mathematical model demonstrated that the model captured the major features of LV remodeling with age and closely approximated experimental results. Specifically, the temporal progression of the LV interior and exterior dimensions demonstrated the same trend and order-of-magnitude change as our experimental results. In conclusion, we present here a validated mathematical model of cardiac aging that applies the thick-wall theory and stretch-induced tissue growth to LV remodeling with age.
Highlights
Over 70% of 50 million Americans over 60 years of age have cardiovascular disease (CVD) [1,2]
While most studies focus on the myocyte contribution to cardiac systolic function, indices for systolic function, such as ejection fraction, systolic velocities, and systolic isovolumic acceleration rate, have been shown to have little relation with age in both clinical and animal studies [4,5]
The ventricular wall was modeled as an isotropic and linear elastic material of two constituents, cardiac myocytes and extracellular matrix (ECM) which is represented by collagen
Summary
Over 70% of 50 million Americans over 60 years of age have cardiovascular disease (CVD) [1,2]. CVD prevalence increases with age, and outcomes in older patients with acute coronary syndromes are poor [1,3]. It is important to note, that aging itself, even in the absence of CVD, alters LV structure and function and impairs the ability of the LV to respond to stress and injury. Understanding the mechanisms of cardiac aging has significant clinical relevance. While most studies focus on the myocyte contribution to cardiac systolic function, indices for systolic function, such as ejection fraction, systolic velocities, and systolic isovolumic acceleration rate, have been shown to have little relation with age in both clinical and animal studies [4,5].
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