Heart Failure Differentially Modulates the Effects of Ivabradine on the Electrical Activity of the Sinoatrial Node and Pulmonary Veins

Heart failure (HF) frequently coexists with atrial fibrillation (AF) and dysfunction of the sinoatrial node (SAN), the natural pacemaker. HF is associated with chronic adrenergic stimulation, neurohormonal activation, abnormal intracellular calcium handling, elevated cardiac filling pressure and atrial stretch, and fibrosis. Pulmonary veins (PVs), which are the points of onset of ectopic electrical activity, are the most crucial AF triggers. A crosstalk between the SAN and PVs determines PV arrhythmogenesis. HF has different effects on SAN and PV electrophysiological characteristics, which critically modulate the development of AF and sick sinus syndrome. This review provides updates to improve our current understanding of the effects of HF in the electrical activity of the SAN and PVs as well as therapeutic implications for AF.

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Intracellular Na+ Modulates Pacemaking Activity in Murine Sinoatrial Node Myocytes: An In Silico Analysis

International Journal of Molecular Sciences ◽

10.3390/ijms22115645 ◽

2021 ◽

Vol 22 (11) ◽

pp. 5645

Author(s):

Stefano Morotti ◽

Haibo Ni ◽

Colin H. Peters ◽

Christian Rickert ◽

Ameneh Asgari-Targhi ◽

...

Keyword(s):

Heart Failure ◽

Membrane Potential ◽

In Silico ◽

Sinoatrial Node ◽

In Silico Analysis ◽

Ankyrin B ◽

Deficient Mice ◽

Silico Analysis ◽

Bursting Activity

Background: The mechanisms underlying dysfunction in the sinoatrial node (SAN), the heart’s primary pacemaker, are incompletely understood. Electrical and Ca2+-handling remodeling have been implicated in SAN dysfunction associated with heart failure, aging, and diabetes. Cardiomyocyte [Na+]i is also elevated in these diseases, where it contributes to arrhythmogenesis. Here, we sought to investigate the largely unexplored role of Na+ homeostasis in SAN pacemaking and test whether [Na+]i dysregulation may contribute to SAN dysfunction. Methods: We developed a dataset-specific computational model of the murine SAN myocyte and simulated alterations in the major processes of Na+ entry (Na+/Ca2+ exchanger, NCX) and removal (Na+/K+ ATPase, NKA). Results: We found that changes in intracellular Na+ homeostatic processes dynamically regulate SAN electrophysiology. Mild reductions in NKA and NCX function increase myocyte firing rate, whereas a stronger reduction causes bursting activity and loss of automaticity. These pathologic phenotypes mimic those observed experimentally in NCX- and ankyrin-B-deficient mice due to altered feedback between the Ca2+ and membrane potential clocks underlying SAN firing. Conclusions: Our study generates new testable predictions and insight linking Na+ homeostasis to Ca2+ handling and membrane potential dynamics in SAN myocytes that may advance our understanding of SAN (dys)function.

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Method for recording electrical activity of the sinoatrial node and automatic atrial foci during cardiac catheterization in human subjects

The American Journal of Cardiology ◽

10.1016/0002-9149(80)90121-6 ◽

1980 ◽

Vol 45 (4) ◽

pp. 775-781 ◽

Cited By ~ 68

Author(s):

Robert J. Hariman ◽

Ehud Krongrad ◽

Robert A. Boxer ◽

Melvin B. Weiss ◽

Carl N. Steeg ◽

...

Keyword(s):

Electrical Activity ◽

Cardiac Catheterization ◽

Sinoatrial Node ◽

Human Subjects

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Catecholaminergic automatic activity in the rat pulmonary vein: electrophysiological differences between cardiac muscle in the left atrium and pulmonary vein

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.00256.2009 ◽

2009 ◽

Vol 297 (1) ◽

pp. H102-H108 ◽

Cited By ~ 29

Author(s):

Nicolas Doisne ◽

Véronique Maupoil ◽

Pierre Cosnay ◽

Ian Findlay

Keyword(s):

Membrane Potential ◽

Electrical Activity ◽

Cardiac Muscle ◽

Left Atrium ◽

Pulmonary Vein ◽

Pulmonary Veins ◽

Muscle Membrane ◽

Resting Membrane Potential ◽

Ectopic Activity ◽

Automatic Activity

Ectopic activity in cardiac muscle within pulmonary veins (PVs) is associated with the onset and the maintenance of atrial fibrillation in humans. The mechanism underlying this ectopic activity is unknown. Here we investigate automatic activity generated by catecholaminergic stimulation in the rat PV. Intracellular microelectrodes were used to record electrical activity in isolated strips of rat PV and left atrium (LA). The resting cardiac muscle membrane potential was lower in PV [−70 ± 1 (SE) mV, n = 8] than in LA (−85 ± 1 mV, n = 8). No spontaneous activity was recorded in PV or LA under basal conditions. Norepinephrine (10−5 M) induced first a hyperpolarization (−8 ± 1 mV in PV, −3 ± 1 mV in LA, n = 8 for both) then a slowly developing depolarization (+21 ± 2 mV after 15 min in PV, +1 ± 2 mV in LA) of the resting membrane potential. Automatic activity occurred only in PV; it was triggered at approximately −50 mV, and it occurred as repetitive bursts of slow action potentials. The diastolic membrane potential increased during a burst and slowly depolarized between bursts. Automatic activity in the PV was blocked by either atenolol or prazosine, and it could be generated with a mixture of cirazoline and isoprenaline. In both tissues, cirazoline (10−6 M) induced a depolarization (+37 ± 2 mV in PV, n = 5; +5 ± 1 mV in LA, n = 5), and isoprenaline (10−7 M) evoked a hyperpolarization (−11 ± 3 mV in PV, n = 7; −3 ± 1 mV in LA, n = 6). The differences in membrane potential and reaction to adrenergic stimulation lead to automatic electrical activity occurring specifically in cardiac muscle in the PV.

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Anatomy and physiology of the sinus node

ESC CardioMed ◽

10.1093/med/9780198784906.003.0446 ◽

2018 ◽

pp. 1940-1943

Author(s):

Antonio Zaza

Keyword(s):

Electrical Activity ◽

Temporal Variability ◽

Sinoatrial Node ◽

Sinus Node ◽

Membrane Current ◽

Membrane Channels ◽

Autonomic Balance ◽

Electrical Excitation ◽

Anatomy And Physiology ◽

Mammalian Heart

The sinoatrial node (SAN) is the dominant pacemaker structure in the mammalian heart. It is endowed with robust intrinsic automaticity, providing periodic electrical excitation with a cycle widely modulated by autonomic influences. A number of membrane channels and transporters contribute to the net membrane current supporting SAN electrical activity, whose periodicity is determined by the interplay of two oscillators termed ‘membrane’ and ‘calcium’ clock respectively. This chapter describes the structure of the SAN, the peculiarities of its electrical cycle, the nature and modulation of the underlying clocks, and SAN interaction with atrial muscle. Moreover, the features and determinants of the temporal variability of the pacemaker cycle, clinically used to assess autonomic balance, are briefly discussed.

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Tangential Triangular Resection An Option to Treat the Giant Left Atrium

Innovations Technology and Techniques in Cardiothoracic and Vascular Surgery ◽

10.1097/imi.0b013e3181d8c55c ◽

2010 ◽

Vol 5 (2) ◽

pp. 125-127

Author(s):

Pablo M. A. Pomerantzeff ◽

Carlos M. A. Brandão ◽

Marco A. V. Guedes ◽

Noedir A. G. Stolf

Keyword(s):

Heart Failure ◽

Magnetic Resonance ◽

Left Atrium ◽

Pulmonary Veins ◽

Posterior Wall ◽

Magnetic Resonance Study ◽

Tricuspid Insufficiency ◽

Size Evolution ◽

Giant Left Atrium ◽

Left Atrium Size

A 21-year-old woman presented with congestive heart failure caused by congenital mitral and tricuspid insufficiency, associated with great left atrium enlargement. Transthoracic echo-cardiogram revealed heart dextroversion associated with mitral and tricuspid severe insufficiency and left atrium enlargement (14 cm), confirmed by magnetic resonance study. The left atrium was reduced by a tangential triangular resection of the posterior wall, between the pulmonary veins, suturing the edges of the left atrium with bovine pericardium strip reinforcement. Mitral and tricuspid valves were repaired. The postoperative course was uneventful, and the patient was discharged in the 15th postoperative day. A control magnetic resonance study revealed a 50% reduction in left atrium size. Evolution of left atrium resection is excellent, with low recurrence of arrhythmias, embolism, or heart failure.

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