Cellular level electromechanical modeling and simulation of heart failure

Area of Science:

• Cardiovascular Physiology
• Computational Biology
• Biophysics

Background:

• Heart failure significantly impairs cardiac mechanical function, posing a major physiological challenge.
• Experimental assessment of these effects at the cellular level is complex.
• Understanding electromechanical coupling is crucial for heart failure research.

Purpose of the Study:

• To develop an electromechanical cardiac cell model integrating heart failure data.
• To investigate cellular mechanical properties in both fast and slow contracting myocytes during heart failure.
• To explore the mechanisms linking electrical and mechanical dysfunction in heart failure.

Main Methods:

• Integration of a modified cellular action potential model with experimental heart failure data.
• Incorporation of a modified Hunter-McCulloch-ter Keurs (HMT) mechanical heart cell model.
• Computational simulation of failing cardiac myocytes to assess electromechanical properties.

Main Results:

• Simulations demonstrated that electrical differences in failing cells slow Ca2+ transient relaxation.
• Reduced Ca2+-TnC concentration differences between fast and slow myocytes in failing hearts were observed.
• A decrease in cellular force and potential increases in transmural action potential duration gradients were predicted.

Conclusions:

• Altered electrical properties in heart failure contribute to mechanical dysfunction and reduced contractility.
• Reduced mechanoelectric feedback (MEF) and increased action potential duration (APD) gradients may promote arrhythmia.
• The model provides insights consistent with experimental findings and supports further research at tissue and organ levels.