Abstract 18082: Differences in Ca2+ Cycling in Atrial Myocytes Isolated From Ventricular-Tachypaced Hearts vs. Atrial Tachypaced Hearts: Implication That Aberrant Ca2+ Cycling Contributes More AF Initiation Than to AF Maintenance
Background: We have recently paid much attention to Ca2+ waves in canine and human atrial myocytes that occur only upon rapid pacing, which we have termed “triggered Ca2+ waves”. The temporal character of triggered Ca2+ waves suggests that they are likely to affect action potential duration beat-to-beat, and so could prompt dispersion of repolarization predisposing to reentrant arrhythmias. We therefore asked whether Ca2+ waves are prevalent in atrial myocytes isolated from failing hearts (proarrhythmic substrate) and/or hearts in atrial fibrillation (AF).
Methods: Atrial myocytes were isolated from normal hearts (canine & human), failing hearts (4-6 weeks ventricular tachypaced; canine only) and hearts in atrial fibrillation (canine_5 weeks atrial tachypaced canine hearts; human_in AF), and examined (@ 37°C) for the incidences triggered Ca2+ waves and Ca2+ alternans during pacing at 1000-200ms cyclelengths (CLs) using Ca2+ fluorescent confocal microscopy.
Results: Triggered Ca2+ waves were much more prevalent in atrial myocytes from normal and failing hearts than in atrial myocytes from heart in AF (incidence: 67% of normal canine, 59% of normal human, 75% of failing canine, 9% of canine AF, 14% of human AF). However, isoproterenol was effective in abolishing triggered Ca2+ waves in atrial myocytes from normal and AF hearts, but not in atrial myocytes from failing hearts. While there was less aberrant Ca2+ cycling in atrial myocytes from AF hearts, Ca2+ alternans were proportionally more prevalent in these myocytes compared to that in atrial myocytes from failing and normal hearts (incidence: 21% of normal canine, 34% normal human, 15% failing canine, 27% of canine AF, 76% human AF). Most recently we have found that reactive oxygen species inhibitors (mitoTEMPO, apocynin) significantly suppress (↓ ~80%, p<0.05) the incidence of triggered Ca2+ waves in atrial myocytes from failing heart.
Conclusions: Our results suggest that abnormal Ca2+ cycling in the form of triggered Ca2+ waves, which may be manifest consequent to the oxidative stress that occurs upon heart failure, may play a more prominent role in the initiation of AF, while other mechanisms (i.e., alternans) contribute more after the establishment of AF and its maintenance.
- © 2013 by American Heart Association, Inc.