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Updated: Jun 1, 2026
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Isolation of Human Atrial Myocytes for Simultaneous Measurements of Ca2+ Transients and Membrane Currents
Published on: July 3, 2013
Repolarization alternans reveals vulnerability to human atrial fibrillation
Sanjiv M Narayan1, Michael R Franz, Paul Clopton
1VAMC/Cardiology, University of California-San Diego, 3350 La Jolla Village Dr., San Diego, CA 92161, USA. snarayan@ucsd.edu
Circulation
|June 8, 2011
Summary
Beat-to-beat oscillations in action potential duration (APD) alternans reveal dynamic substrates for atrial fibrillation (AF). These alternans occur more readily at lower rates in persistent and paroxysmal AF patients compared to controls.
Area of Science:
- Cardiology
- Electrophysiology
- Cardiac Arrhythmias
Background:
- The underlying mechanisms of human atrial fibrillation (AF) remain incompletely understood, with abnormal repolarization, specifically action potential duration (APD), implicated.
- A spectrum of AF vulnerability exists, ranging from individuals without AF to those with paroxysmal and persistent forms.
Purpose of the Study:
- To investigate the hypothesis that beat-to-beat oscillations in APD, known as APD alternans, contribute to AF substrates.
- To determine if APD alternans can explain the varying susceptibility to AF across different patient groups.
Main Methods:
- Recorded left and right atrial APD in 33 subjects (12 persistent AF, 13 paroxysmal AF, 8 controls) during programmed electrical stimulation.
- Pacing was performed at decreasing cycle lengths (600 to 500 ms, then faster until AF initiation) to assess APD restitution and alternans.
- Analyzed the relationship between APD alternans, complex oscillations, and the initiation of AF at different pacing rates.
Main Results:
- APD alternans manifested at significantly faster rates in controls (cycle length 218±33 ms) compared to paroxysmal AF (372±72 ms) and persistent AF (411±94 ms) patients.
- In AF patients, APD alternans occurred at rates as slow as 100-120 bpm and were independent of APD restitution.
- Complex oscillations, preceding AF, also occurred at progressively faster rates in controls versus paroxysmal AF versus persistent AF patients.
Conclusions:
- Atrial APD alternans serve as a dynamic substrate for AF, appearing most readily at lower rates in persistent and paroxysmal AF patients compared to controls.
- APD alternans consistently preceded all observed AF episodes and were absent when AF did not initiate.
- Further research is needed to elucidate the cellular mechanisms driving APD alternans near physiological heart rates.
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