Atrioventricular nodal reverse facilitation in connexin40-deficient mice

Zhu, Wei; Saba, Samir; Link, Mark S.; Bak, Eugene; Homoud, Munther K.; Estes, N.A. Mark; Paul, David L.; Wang, Paul J.

doi:10.1016/j.hrthm.2005.07.022

Cited by 9 publications

(9 citation statements)

References 28 publications

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“…Similarly, the ability to alter mice genetically has provided an important tool to better understand mechanisms of pathological process. In the last 8 years, techniques to record intracardiac electrical activity, as well as the ability to deliver impulses to right atrium and ventricle of mice using programmed stimulation, have been developed [46,73,75]. To perform the electrophysiological studies, a 2Fr octopolar ring electrode catheter with 0.5mm electrode width and 0.5mm interelectrode distance is introduced into the right atrium and ventricle of the mouse via the right external jugular vein.…”

Section: Remodelling At the San And Avnmentioning

confidence: 99%

Hyperhomocysteinemia and Sudden Cardiac Death: Potential Arrhythmogenic Mechanisms

Maldonado¹,

Soni²,

Todnem³

et al. 2010

CVP

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Elevated levels of serum homocysteine (Hcy) resulting in hyperhomocysteinemia (HHcy) have been implicated in cardiac pathological conditions including: coronary heart disease (CHD), acute myocardial infarction, arrhythmogenesis and sudden cardiac death (SCD). The mechanisms by which HHcy leads to arrhythmogenesis and SCD are unknown. Novel findings indicate that Hcy is an agonist of the N-methyl-D-aspartate receptor (NMDA-R), known to be present in cardiac tissue, and when activated, increases intracellular calcium leading to increased cell excitability. Also, HHcy induces oxidative stress in cardiac cells and activates matrix metalloproteinases (MMPs) that degrade cell membranes and proteins. Here we review the literature relevant to HHcy-induced oxidative stress leading to cardiac tissue remodelling that may adversely affect cell-to-cell impulse conduction, in particular on the heart's specialized conduction system, and may provide substrate for arrhythmogenesis and SCD. Efficacy of B vitamin supplementation in patient populations with HHcy and CHD is also reviewed.

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Section: Remodelling At the San And Avnmentioning

confidence: 99%

Hyperhomocysteinemia and Sudden Cardiac Death: Potential Arrhythmogenic Mechanisms

Maldonado¹,

Soni²,

Todnem³

et al. 2010

CVP

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“…Obviously, Cx expression patterns will influence propagation between Purkinje and ventricular cells. In fact, recent studies suggest that Cx40 deficiency in mice is accompanied by right Bundle branch block presumably due to loss of Cx40 in Purkinje cells [9,10]. …”

Section: Connexin 4×mentioning

confidence: 99%

The Purkinje cell; 2008 style

Dun

Boyden

2008

Journal of Molecular and Cellular Cardiology

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Cardiac Purkinje fibers, due to their unique anatomical location, cell structure and electrophysiologic characteristics, play an important role in cardiac conduction and arrhythmogenesis. Purkinje cell action potentials are longer than their ventricular counterpart, and display two levels of resting potential. Purkinje cells provide for rapid propagation of the cardiac impulse to ventricular cells and have pacemaker and triggered activity, which differs from ventricular cells. Additionally, a unique intracellular Ca 2+ release coordination has been revealed recently for the normal Purkinje cell. However, since the isolation of single Purkinje cells is difficult, particularly in small animals, research using Purkinje cells has been restricted. This review concentrates on comparison of Purkinje and ventricular cells in the morphology of the action potential, ionic channel function and molecular determinants by summarizing our present day knowledge of Purkinje cells.

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“…An increasing body of evidence suggests that inflammation can induce autonomic remodeling, resulting in the electrical remodeling for the initiation and maintenance of AF (32). Nerve sprouting and sympathetic hyperinnervation as an autonomic remodeling process, characterized by increased GAP-43-positive staining nerves in the atrium, have been demonstrated previously in animal models of AF, which is induced by either rapid pacing (6,27) or occurs after MI (18,31).…”

Section: Discussionmentioning

confidence: 82%

“…The methodology of the study has been described previously in detail (32). The baseline six-lead surface ECG was obtained by subcutaneous placement of 24-gauge needles in each limb and was monitored continuously during the procedure.…”

Section: Methodsmentioning

confidence: 99%

Simvastatin attenuates sympathetic hyperinnervation to prevent atrial fibrillation during the postmyocardial infarction remodeling process

Zhu

et al. 2012

Journal of Applied Physiology

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Simvastatin attenuates sympathetic hyperinnervation to prevent atrial fibrillation during the postmyocardial infarction remodeling process. J Appl Physiol 113: 1937-1944, 2012. First published September 13, 2012 doi:10.1152/japplphysiol.00451.2012.-Statin, as a 3-hydroxy-3-methyl-glutaryl-CoA reductase inhibitor, has been shown to prevent atrial fibrillation (AF) due to its anti-inflammatory and antioxidant effects. However, it is still not known whether statin can improve autonomic remodeling to prevent AF. In the present study, using an in vivo rat myocardial infarction (MI) model, we aimed to test whether simvastatin can attenuate nerve sprouting and sympathetic hyperinnervation to prevent AF during the post-MI remodeling process. Our data demonstrate that simvastatin, delivered 3 days after MI for 4 wk, can result in significant decreases in plasma levels of both TNF-␣ (239 Ϯ 23 pg/ml) and IL-1␤ (123 Ϯ 11 pg/ml) compared with MI rats without therapy (TNF-␣, 728 Ϯ 57 pg/ml; IL-1␤, 213 Ϯ 21 pg/ml; P Ͻ 0.05), which, however, were still higher than sham-operated rats (TNF-␣, 194 Ϯ 20 pg/ml; IL-1␤, 75 Ϯ 8 pg/ml; P Ͻ 0.05). The similar pattern of changes in inflammation responses was also observed in TNF-␣ and IL-1␤ protein expression in the left atrium free wall. The suppressed inflammation responses were associated with reduced superoxide and malondialdehyde generation in the atrium. These changes account for decreases in neural growth factor expression at levels of both mRNA (1.2 Ϯ 0.09 AU vs. MI group, 1.78 Ϯ 0.16 AU) and protein (1.57 Ϯ 0.17 AU vs. MI group, 2.24 Ϯ 0.19 AU; P Ͻ 0.05), thus resulting in reduced nerve sprouting and sympathetic hyperinnervation. Accordingly, the rate adaptation of the atrial effective refractory period also recovered, leading to the decreased inducibility of AF. These data suggest that simvastatin administration after MI can prevent AF through reduced sympathetic hyperinnervation. atrial fibrillation; autonomic remodeling; inflammation; statin ATRIAL FIBRILLATION (AF) IS a common cardiac arrhythmia in clinical practice, which is associated with a higher mortality as well as an increased morbidity due to a significantly higher incidence of stroke, congestive heart failure, and tachycardiainduced cardiomyopathy, leading to an impaired quality of life (4). In the patients with myocardial infarction (MI), a cardiacremodeling process often results in a high incidence of AF (3).A growing body of evidence shows that inflammation and/or oxidative stress play an important role in the pathological process of AF (20); however, the underlying mechanism via which inflammation causes AF is still not well known. Interestingly, in a tachycardiac pacing-induced AF animal model, there shows a significant increase in nerve sprouting and sympathetic hyperinnervation, characterized by a higher density of GAP-43-and tyrosine hydroxylase (TH)-positive staining nerves in the atrium (6, 27). Furthermore, nerve sprouting and sympathetic hyperinnervation are also observed in MI animal models where GAP-43...

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Atrioventricular nodal reverse facilitation in connexin40-deficient mice

Cited by 9 publications

References 28 publications

Hyperhomocysteinemia and Sudden Cardiac Death: Potential Arrhythmogenic Mechanisms

Hyperhomocysteinemia and Sudden Cardiac Death: Potential Arrhythmogenic Mechanisms

The Purkinje cell; 2008 style

Simvastatin attenuates sympathetic hyperinnervation to prevent atrial fibrillation during the postmyocardial infarction remodeling process

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