Cardiac mechanoenergetics in silico

Area of Science:

• Cardiovascular Physiology
• Biophysics
• Biochemistry

Background:

• Cardiac muscle function relies on intricate biochemical and mechanical processes.
• Understanding the link between intracellular energy metabolism and mechanical contraction is crucial for cardiac health.
• Existing models often simplify the complex interplay of energy fluxes and mechanical output.

Purpose of the Study:

• To investigate the relationship between intracellular biochemical processes and cardiac muscle mechanical contraction.
• To model energy regulation, biochemical to mechanical energy transformation, and ventricular function.
• To establish correlations between left ventricular function and cellular-level mechanical and energetic parameters.

Main Methods:

• Analysis of intracellular energy fluxes between mitochondria and myofibrils.
• Development and application of a cross-bridge model for energy transformation.
• Correlation analysis between ejection fraction, sarcomere strain, stress, ATP consumption, and oxygen consumption.

Main Results:

• Cardiac metabolic stability is reproducible via a feedback mechanism balancing ATP production and consumption.
• A cross-bridge model successfully replicates the linear relationship between oxygen consumption and stress-strain area.
• Established a correlation between left ventricular ejection fraction and heterogeneity in sarcomere strain, stress, and ATP consumption.
• Theoretically predicted the linear relationship between oxygen consumption and pressure-volume area from oxygen consumption and stress-strain area.

Conclusions:

• Intracellular physiological processes are fundamentally interwoven with cardiac muscle macrovariables.
• Feedback regulation of energy metabolism is key to cardiac metabolic stability.
• The developed cross-bridge model provides a mechanistic link between biochemical energy use and mechanical function in the heart.