Heart Failure Differentially Modulates Natural (Sinoatrial Node) and Ectopic (Pulmonary Veins) Pacemakers: Mechanism and Therapeutic Implication for Atrial Fibrillation

Figures

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  Figure 1. Effects of stretch on the electrical activity and the action potential (AP) configuration of the pulmonary veins (PVs). (A) Stretch force dependently increased the firing rate of the spontaneous activity of the PVs. (B) Superimposed tracings of PVs in which stretch force dependently decreased the amplitude and duration of the AP and induced delayed afterdepolarization (asterisk). (C) Stretch induced early afterdepolarization and burst firings in PVs. Arrow indicates electrical stimuli (2 Hz). “Modified with permission from Chang, S.L., et al. [58]”.

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  Figure 2. Sinoatrial node (SAN)-pulmonary vein (PV) electrical interaction. The schematic drawings show the simultaneous recordings (arrows) at the SAN and PVs in intact (Panel A) and disconnected (Panel B) SAN-PV preparations before and after the treatment of Anemonia sulcata toxin (ATX)-II. Burst firings (right middle panel) and early afterdepolarizations (EADs, right bottom panel) were induced in isolated PV preparation after being separated and superfused with ATX-II. The asterisks indicate burst firings and the arrowhead indicates EAD. “Modified with permission from Chen, Y.C., et al. [26]”.

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  Figure 3. Intracellular Ca2+ transient (Ca2+i) and the calcium stores from the control and heart failure (HF) pulmonary vein (PV) cardiomyocytes. HF PV cardiomyocytes with (panel A) or without (panel B) pacemaker activity have a larger Ca2+i and calcium stores measured from caffeine (20 mM)-induced Ca2+i than control PV cardiomyocytes with or without pacemaker activity, respectively. “Modified with permission from Chang, S.L., et al. [91]”.

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  Figure 4. Effects of heart failure (HF) on sinoatrial node (SAN) electrical activity and pulmonary vein (PV) arrhythmogenesis. There is SAN to PV electric conduction in the control SAN-PV preparation (top left panel). SAN automaticity exit blocks (asterisks, bottom left panel) and SAN-PV conduction blocks (arrows, top right panel) with absence of PV electrical activity were found in HF SAN-PV preparations. Bottom right panel shows delayed afterdepolarizations (DADs; arrows) in a HF SAN-PV preparation. In top left panel, dashed lines indicate the peaks of SAN electrical activity. “Modified with permission from Chan, C.S., et al. [90]”.

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  Figure 5. Effects of ivabradine on the electrical activity of control and heart failure (HF) sinoatrial node (SAN)-pulmonary vein (PV) preparations and PV arrhythmogenesis. (A) SAN automaticity exit blocks (asterisks) (top left panel) and SAN-PV conduction blocks (arrows) (bottom left panel) in HF SAN-PV preparations after ivabradine administration. Bottom right panel shows delayed afterdepolarizations (arrows) in HF SAN-PV preparations after ivabradine administration. (B) Left panel shows that isoproterenol (1 µM) accelerated electrical activity in SAN-PV preparation without change of the direction of SAN-PV electrical conduction. Right panel shows that the direction of electrical conduction between the SAN and PV reversed in HF SAN-PV preparation in the presence of isoproterenol (1 µM) with ivabradine (10 µM). Dashed lines indicate the peaks of SAN electrical activity. “Modified with permission from Chan, C.S., et al. [90]”