Feedback control of calcium driven alternans in cardiac myocytes

Area of Science:

• Cardiology
• Computational Biology
• Biophysics

Background:

• Cardiac alternans, a beat-to-beat alternation in action potential duration (APD), is linked to ventricular fibrillation.
• Previous research shows APD alternans can arise from nonlinear diastolic interval dependence and be controlled by pacing.
• Alternatively, unstable intracellular calcium (Ca) cycling can also drive alternans.

Purpose of the Study:

• To investigate the efficacy of APD feedback control in suppressing cardiac alternans driven by unstable Ca cycling.
• To analyze the influence of Ca-voltage coupling on feedback control effectiveness.
• To evaluate feedback control in coupled cell systems and its impact on spatial alternans patterns.

Main Methods:

• Computational modeling of cardiac myocyte electrophysiology and intracellular Ca dynamics.
• Simulation of APD feedback control strategies under various conditions.
• Analysis of coupled two-cell and multi-cellular systems to study spatial alternans.

Main Results:

• APD feedback control can suppress Ca-driven alternans, though its effectiveness depends on Ca-voltage coupling.
• In coupled systems, APD control can induce spatially out-of-phase alternans.
• The study identifies conditions for the emergence of these out-of-phase patterns and assesses control efficacy.

Conclusions:

• APD feedback control is a potential strategy for managing cardiac alternans, even when Ca cycling is the primary driver.
• Understanding the interplay between Ca dynamics and electrical activity is crucial for optimizing control strategies.
• Feedback control can influence spatial alternans patterns in multi-cellular cardiac tissue.