Electrolyte disturbances differentially regulate sinoatrial node and pulmonary vein electrical activity: A contribution to hypokalemia- or hyponatremia-induced atrial fibrillation
Introduction
Atrial fibrillation (AF) is the most common sustained arrhythmia and is associated with higher risk of stroke, heart failure, cardiac mortality, and overall mortality.1, 2 Clinical studies have shown that lower serum concentrations of potassium ([K+] <3.5 mM) are associated with a higher risk of AF.3 Diuretic therapy is the most common cause of K+ deficiency,4 which also commonly occurs during hemodialysis treatment sessions.5, 6 Low [K+] levels cause cellular hyperpolarity, which may increase cardiac arrhythmogenesis.7 Hypokalemia-induced hyperexcitability is clinically manifested by an increase in supraventricular and ventricular ectopy.8 Similarly, hyponatremia (serum sodium ([Na+]) level <135 mM)9 is common in renal disease or heart failure10, 11 and can predispose patients to the development of AF.12, 13 Patients with AF have been found to have significantly lower serum [Na+] than patients without AF, and acute reductions in serum [Na+] may cause paroxysmal AF episodes.14 Hyponatremia due to water retention increases atrial stretch, which can increase vulnerability to atrial arrhythmia.15, 16 However, the mechanisms by which hyponatremia and hypokalemia increase AF have yet to be elucidated.
Pulmonary veins (PVs) play a critical role in the pathophysiology of AF. Previous studies have shown that PVs behave high arrhythmogenicity due to enhanced triggered and spontaneous activities.17 Hypokalemia increases the occurrence of supraventricular ectopic beats, which suggests that hypokalemia may modulate PV arrhythmogenesis to facilitate the occurrence of paroxysmal AF.18 Moreover, hypokalemia has been shown to regulate sinoatrial node (SAN) electrical activity with a decrease in automaticity.19 Sick sinus syndrome plays a critical role in the genesis of AF,20, 21 and SAN dysfunction can enhance PV arrhythmogenesis, which may contribute to the high incidence of AF in sick sinus syndrome.22 Therefore, hypokalemia or hyponatremia may change SAN and PV electrical activity and facilitate the genesis of AF. In this study, we investigated the effects of lower [K+] or [Na+] on the electrophysiologic characteristics of SANs and PVs, and evaluated the potential underlying mechanisms.
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Animal and tissue preparation
This study was approved by the local ethics review board of our hospital (IACUC-102-003) and conformed to the Institutional Guidelines for the Care and Use of Laboratory Animals and the Guide for the Care and Use of Laboratory Animals published by the United States National Institutes of Health (NIH Publication No. 85-23, revised 1996). As described previously, 10 male New Zealand white rabbits (weight 2–3 kg) were euthanized by intravenous injection of sodium pentobarbital (100 mg/kg).23 The
Effects of low [K+] on SAN and PV electrical activity and diastolic tension
Compared to baseline ([K+] of 4 mM), a low [K+] (3.5, 3, 2.5, and 2 mM) decreased PV beating rates but increased diastolic tension in 9 PVs (Figure 1). A low [K+] of 2.5 mM significantly increased the occurrence of DAD and burst firing (0% vs 55%, P <.05) with a rate up to 6.5 Hz (4.0 ± 0.6 Hz at 2.5 mM, and 4.8 ± 0.7 Hz at 2 mM), but it insignificantly induced the occurrence of EAD (0% vs 22%, P >.05) in 9 PVs (Figure 2A). In addition, burst firings (n = 5) were followed by a pause or
Discussion
Electrolytes play a pivotal role in the genesis of APs, and disturbances in ion homeostasis are common with cardiac arrhythmia. Electrical activity of the heart is composed of transmembrane ionic movement, and electrolytes disturbance can contribute to an increased susceptibility to AF. In this study, we found that a low [K+] decreased the beating rate and induced triggered activity in the PVs and SANs. Previous study has also shown that hypokalemia significantly slows SAN upstroke and reduces
Conclusion
Hypokalemia and hyponatremia differentially modulate SAN and PV electrical properties. The slowing of SAN beating rate and the increase in PV burst firings with low [K+] or low [Na+] contribute to the high occurrence of AF during hypokalemia or hyponatremia.
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Cited by (0)
Drs. Lu and Cheng contributed equally to this manuscript. This study was supported by Grants NSC101-2314-B-040-017-MY2, NSC102-2314-B-016-029-MY2, NSC102-2325-B-010-005, NSC102-2628-B-038-002-MY3, and 103-2314-B-281-005-MY2 from the National Science Council of Taiwan; Grants CGH-MR-A10219, CGH-MR-A10221, CGH-MR-A10222, and CGH-MR-103-05 from Cathay General Hospital; and Grants 103swf05 and 103-wf-eva-02 from Wan Fang Hospital, Taipei Medical University.