Multiscale Computational Analysis of Right Ventricular Mechanoenergetics

Area of Science:

• Cardiovascular Physiology
• Computational Biology
• Biomedical Engineering

Background:

• Right ventricular (RV) failure is a consequence of pressure overload, marked by impaired mechanical and energetic function.
• The impact of cellular and tissue changes on overall RV function during pressure overload remains unclear.

Purpose of the Study:

• To investigate how myofiber mechanics and mitochondrial energetics influence organ-level RV function under pressure overload.
• To utilize a multiscale cardiovascular model to explore these relationships.

Main Methods:

• Developed a multiscale computational model integrating intracellular metabolite concentrations, actin-myosin cross-bridging, and myocardial tissue mechanics.
• Coupled a biventricular heart model with lumped parameter circulations.
• Simulated three distinct pressure overload scenarios and compared model outputs with experimental data.

Main Results:

• The computational model successfully replicated cardiovascular physiology and pathophysiology, from mild RV dysfunction to RV failure.
• Confirmed that the RV maintains cardiac output (CO) when solely subjected to pressure overload.
• Predicted that decreased CO in RV failure necessitates changes in RV active myofiber mechanics or metabolite concentrations.

Conclusions:

• Multiscale modeling provides insights into RV function under pressure overload.
• Myofiber mechanics and mitochondrial energetics are critical determinants of RV performance and failure.
• Specific alterations in these intrinsic RV properties, not just pressure overload, drive reduced cardiac output.