Mathematical modeling of left ventricular dimensional changes in mice during aging

Area of Science:

• Cardiovascular research
• Biomechanical engineering
• Gerontology

Background:

• Cardiac aging is associated with left ventricular (LV) diastolic dysfunction.
• Increased LV wall stiffness, influenced by extracellular matrix (ECM) composition, contributes to diastolic dysfunction.

Purpose of the Study:

• To develop and validate a mathematical model predicting LV dimension and wall stiffness changes during cardiac aging.
• To investigate the impact of ECM composition on cardiac aging using a computational approach.

Main Methods:

• Developed a mathematical model integrating mechanical laws and experimental data from aging wild-type C57/BL6J mice (7.3 to 34.0 months).
• Model based on thick wall theory and stretch-induced tissue growth, treating the LV as an elastic composite.
• Simulations performed using Matlab, with initial conditions based on young mouse data.

Main Results:

• The mathematical model accurately captured key features of LV remodeling with age.
• Simulated LV dimensions and wall stiffness changes closely approximated experimental results.
• Model demonstrated the temporal progression of LV interior and exterior dimensions consistent with experimental data.

Conclusions:

• A validated mathematical model for cardiac aging has been developed.
• The model effectively applies thick-wall theory and stretch-induced tissue growth to understand LV remodeling.
• This approach provides insights into age-related changes in cardiac mechanics and ECM composition.