Basic/Translational Science -> Cell Physiology, Pharmacology, and Signaling D-PO02 - Poster Session II (ID 47) Poster

D-PO02-016 - Atrial Myocytes From Patients With Paroxysmal Atrial Fibrillation Are More Susceptible To Action Potential Alternans (ID 161)

Abstract

Background: Alternans within a cardiomyocyte describes a beat to beat switching of electrical parameters between two states and is suggested to contribute to atrial arrhythmogenesis.
Objective: To investigate if atrial myocytes from patients with paroxysmal atrial fibrillation (pAF) are more susceptible to electrical alternans and to elucidate potential underlying mechanisms.
Methods: Action potentials (patch clamp) and [Ca2+]i (Fluo3) were measured in right atrial myocytes isolated from patients with sinus rhythm (Ctl; n=16) and pAF (n=8). Action potential (AP) and calcium transient (CaT) alternans were detected and spectrally analyzed with custom-written software.
Results: AP duration at various pacing frequencies was unchanged between pAF and Ctl patients, indicating an absence of electrical remodeling in pAF. A higher incidence of CaT alternans (46% vs 18%; P=0.08) and AP alternans (82% vs 52%; P<0.05) was observed in pAF myocytes compared to Ctl (Fig. A). In addition, the lowest frequency at which AP alternans was detected was significantly lower in pAF (2.4 ± 0.8 vs 4.6 ± 0.6 Hz; n/N= 9/6 pAF vs 13/12 Ctl; P<0.05). A similar trend was also observed in the threshold frequency for CaT alternans (4.2 ± 0.9 vs 5.3 ± 1.0 Hz; n/N= 6/4 pAF vs 4/4 Ctl; Fig. B). AP restitution was unchanged (Fig. C), implying that CaT alternans is likely the major driving force for AP alternans development (Fig. D).
Conclusion: Here we demonstrate for the first time an enhanced susceptibility to cellular electrical alternans in atrial myocytes from pAF patients. This may disturb excitation-propagation and therefore contribute to the arrhythmogenic substrate in patients presenting with pAF.

Collapse