Abstract 741: Enhanced Early Afterdepolarization Formation Within Superfused Canine Pulmonary Vein Sleeves Following Prolonged Rapid Ventricular Pacing
Early afterdepolarizations (EADs) have been demonstrated to initiate triggered arrhythmia within pulmonary veins (PVs). Microelectrode recordings were utilized during tachycardia-pause pacing, norepinephrine (NE) administration, and acetylcholine (Ach) administration to assess EAD and triggered arrhythmia formation within superfused PVs from normal (N=13) and ventricular-paced (35 days, 180 bpm)(N=11) dog hearts. Ventricular pacing produced elevation of left atrial pressure (25 ± 4 vs. 10 ± 4 mmHg, p < 0.05). When compared to PV cells from normal hearts (N=13), PV cells from paced hearts were depolarized (−69 ± 1 vs. −72 ± 1 mV, p=0.007), reduced in amplitude (78 ± 1 vs. 90 ± 1 mV, p=0.01), and shortened at 50% and 90% of repolarization (46 ± 2 and 115 ± 2 vs. 56 ± 2 and 139 ± 3 msec, p=0.005 and p=0.0001, respectively). Tachycardia-pause pacing induced larger EAD formation in paced vs. normal hearts (Δ 84 ± 10 vs. 55 ± 8 msec, p=0.02; take-off potential = −52 ± 3 vs. −60 ± 4 mV, p<0.01). The first-order decay for enhanced EAD formation following tachycardia-pause pacing (restitution) was slower for paced vs. normal hearts (T1/2 = 0.38 ± 0.02 vs. 1.38 ± 0.11 sec; p=0.02), suggesting a delayed recovery of an enhanced calcium transient and/or an increased Na-Ca exchange current. The T1/2 was reduced by 10−8M NE in normal hearts (0.32 ± 0.02 sec, p< 0.05) and in paced hearts (0.87 ± 0.13 sec), but remained prolonged for paced hearts vs. normal hearts (p<0.01). Increasing Ca+2 o (1.35 to 5.4 mM) enhanced EAD formation, but slowed EAD restitution only in the paced (T1/2 = 1.69 ± 0.8 sec, p < 0.05), not in normal hearts (T1/2 = 0.38 ± 0.06 sec). Ach (10−8, 10−7 M) produced equivalent action potential shortening in each group. Tachycardia-pause pacing induced short-bursts of triggered firing (1–3 beats) and ryanodine (10 μM) completely suppressed EAD formation/triggering in both groups. The present studies demonstrate shortened action potential durations and enhanced EAD formation in canine PV sleeves following prolonged ventricular pacing. EAD formation and triggered arrhythmias are further accentuated by hypercalcemia. An altered calcium transient produced by prolonged elevations in left atrial pressure facilitates EAD formation and may enhance triggered firing from the PVs.