Heart Failure Enhanced Pulmonary Vein Arrhythmogenesis and Dysregulated Sodium and Calcium Homeostasis with Increased Calcium Sparks

HF Enhanced PV Arrhythmogenesis. Introduction: Late sodium currents and intracellular Ca2+ (Ca-i(2+)) dynamics play an important role in arrhythmogenesis of pulmonary vein (PV) and heart failure (HF). It is not clear whether HF enhances PV arrhythmogenesis through modulation of Ca2+ homeostasis and increased late sodium currents. The aim of this study was to investigate the sodium and calcium homeostasis in PV cardiomyocytes with HF. Methods and Results: Whole-cell patch clamp was used to investigate the action potentials and ionic currents in isolated rabbit single PV cardiomyocytes with and without rapid pacing induced HF. The Ca-i(2+) dynamics were evaluated through fluorescence and confocal microscopy. As compared to control PV cardiomyocytes (n = 18), HF PV cardiomyocytes (n = 13) had a higher incidence of delayed afterdepolarization (45% vs 13%, P < 0.05) and faster spontaneous activity (3.0 +/- 0.2 vs 2.1 +/- 0.2 Hz, P < 0.05). HF PV cardiomyocytes had increased late Na+ currents, Na+/Ca2+ exchanger currents, and transient inward currents, but had decreased Na+ currents or L-type calcium currents. HF PV cardiomyocytes with pacemaker activity had larger Ca-i(2+) transients (R410/485, 0.18 +/- 0.04 vs 0.11 +/- 0.02, P < 0.05), and sarcoplasmic reticulum Ca2+ stores. Moreover, HF PV cardiomyocytes with pacemaker activity (n = 18) had higher incidence (95% vs 70%, P < 0.05), frequency (7.8 +/- 3.1 vs 2.3 +/- 1.2 spark/mm/s, P < 0.05), amplitude (F/F-0, 3.2 +/- 0.8 vs 1.9 +/- 0.5, P < 0.05), and longer decay time (65 +/- 3 vs 48 +/- 4 ms, P < 0.05) of Ca2+ sparks than control PV cardiomyocytes with pacemaker activity (n = 18). Conclusions: Dysregulated sodium and calcium homeostasis, and enhanced calcium sparks promote arrhythmogenesis of PV cardiomyocytes in HF, which may play an important role in the development of atrial fibrillation. (J Cardiovasc Electrophysiol, Vol. 22, pp. 1378-1386, December 2011)