Synchronization of Triggered Waves in Atrial Tissue.

Area of Science:

• Cardiac Electrophysiology
• Computational Biology
• Cellular Physiology

Background:

• Rapid atrial pacing can induce calcium (Ca) waves at the cell boundary, known as triggered waves.
• These triggered waves originate from L-type Ca channel influx during the action potential.
• The impact of triggered waves on atrial tissue electrophysiology remains largely unknown.

Purpose of the Study:

• To develop a phenomenological model of Ca cycling in atrial myocytes that incorporates triggered wave formation.
• To investigate the conditions under which triggered waves induce abnormal electrical activity in atrial tissue.
• To identify mechanisms responsible for the synchronization of triggered waves in cardiac tissue.

Main Methods:

• Development of a phenomenological computational model of Ca cycling in atrial myocytes.
• Simulation of triggered wave formation and propagation within the model.
• Analysis of triggered wave synchronization mechanisms and their impact on action potential duration (APD) in simulated cardiac tissue.

Main Results:

• Triggered waves must synchronize across large cell populations to cause abnormal electrical activity.
• Two synchronization mechanisms were identified: cycle length variability and a slow feedback mechanism involving APD and triggered wave initiation.
• Cycle length variability amplifies APD through triggered wave synchronization.
• The slow feedback mechanism leads to spatially discordant APD alternans, potentially serving as a substrate for atrial fibrillation.

Conclusions:

• Triggered wave synchronization is a critical factor for their arrhythmogenic potential in atrial tissue.
• APD alternans and spatially discordant patterns arise from specific triggered wave synchronization mechanisms.
• These findings suggest a novel mechanism linking cellular Ca dynamics to the initiation of atrial fibrillation.