scholarly journals Transcriptomic profiling of atrial fibrillation canine models at disease onset

2021 ◽  
Author(s):  
Francis Leblanc ◽  
Faezeh Vahdati Hassani ◽  
Laura Liesinger ◽  
Xiaoyan Qi ◽  
Patrice Naud ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Striated Muscle ◽  
Early Stage ◽  
Disease Onset ◽  
Atrioventricular Node ◽  
Ventricular Rate ◽  
Ribonucleic Acids ◽  
Electrophysiological Properties ◽  
Molecular Events ◽  
Canine Models

ABSTRACTAtrial fibrillation (AF), the most common arrhythmia with an overall prevalence of 0.51%, is associated with increased morbidity and mortality, as well as important healthcare costs. AF develops over many years and is often associated with substantial changes in the structural and electrophysiological properties of the atria. Because AF may lack subclinical symptoms at onset, it has been difficult to study the molecular and cellular events associated with earlier stages of this pathology in humans. Here, we characterized comprehensively the transcriptomic changes that occur in the atria of two robust canine AF models, electrically maintained AF without and with a controlled ventricular rate achieved by radiofrequency-ablation of the atrioventricular node/ventricular pacing, after one week of maintenance. Our RNA-sequencing experiments identified thousands of genes that are differentially expressed, including a majority that have never before been implicated in AF. Gene set enrichment analyses identified known (e.g. extracellular matrix structure organization) but also many novel pathways (e.g. muscle structure development, striated muscle cell differentiation) that may play a role in tissue remodeling and/or cellular trans-differentiation. Of interest, we found dysregulation of a cluster of non-coding ribonucleic acids (RNAs), including many microRNAs but also the MEG3 long non-coding RNA orthologue, located in the syntenic region of the imprinted human DLK1-DIO3 locus. Our results capture molecular events that occur at an early stage of disease development using well-characterized animal models, and may therefore inform future studies that aim to further dissect the causes of AF and factors involved in its progression in humans.

scholarly journals Transcriptomic Profiling of Canine Atrial Fibrillation Models after One Weekof Sustained Arrhythmia

2021 ◽  
Author(s):  
Francis J.A. Leblanc ◽  
Faezeh Vahdati Hassani ◽  
Laura Liesinger ◽  
Xiaoyan Qi ◽  
Patrice Naud ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Striated Muscle ◽  
Early Stage ◽  
Atrioventricular Node ◽  
Differentially Expressed ◽  
Ventricular Rate ◽  
Glutamate Signaling ◽  
Molecular Events ◽  
Non Coding Rna ◽  
Long Non Coding Rna

Background - Atrial fibrillation (AF), the most common sustained arrhythmia, is associated with increased morbidity, mortality, and health-care costs. AF develops over many years and is often related to substantial atrial structural and electrophysiological remodeling. AF may lack symptoms at onset and atrial biopsy samples are generally obtained in subjects with advanced disease, so it is difficult to study earlier-stage pathophysiology in humans. Methods - Here, we characterized comprehensively the transcriptomic (miRNAseq and mRNAseq) changes in the left atria of two robust canine AF-models after one week of electrically-maintained AF, without or with ventricular rate-control via atrioventricular node-ablation/ventricular pacing. Results - Our RNA-sequencing experiments identified thousands of genes that are differentially expressed, including a majority that have never before been implicated in AF. Gene-set enrichment analyses highlighted known (e.g. extracellular matrix structure organization) but also many novel pathways (e.g. muscle structure development, striated muscle cell differentiation) that may play a role in tissue remodeling and/or cellular trans-differentiation. Of interest, we found dysregulation of a cluster of non-coding RNAs, including many microRNAs but also the MEG3 long non-coding RNA orthologue, located in the syntenic region of the imprinted human DLK1-DIO3 locus. Interestingly (in the light of other recent observations), our analysis identified gene-targets of differentially expressed microRNAs at the DLK1-DIO3 locus implicating glutamate signaling in AF pathophysiology. Conclusions - Our results capture molecular events that occur at an early stage of disease development using well-characterized animal models, and may therefore inform future studies that aim to further dissect the causes of AF in humans.

Augmented Ventricular Rate Following Verapamil Treatment for Atrial Fibrillation with Wolff-Parkinson-White Syndrome

PEDIATRICS ◽  
1983 ◽  
Vol 72 (2) ◽  
pp. 245-246
Author(s):  
Thomas W. Rowland
Keyword(s):  
Atrial Fibrillation ◽  
Supraventricular Tachycardia ◽  
Refractory Period ◽  
Atrioventricular Node ◽  
Ventricular Rate ◽  
Paroxysmal Supraventricular Tachycardia ◽  
First Line ◽  
Ventricular Preexcitation ◽  
Line Drug ◽  
Wolff Parkinson White Syndrome

Verapamil has gained increasing acceptance as a first-line drug in the treatment of paroxysmal supraventricular tachycardia in both adults1 and children.2-4 Conversion to sinus rhythm in more than 90% of cases has been reported, an effect related to the drug's prolongation of refractory period and conduction through the atrioventricular node. The electrophysiologic effects of verapamil on accessory atrioventricular conduction pathways are more variable, and in some patients the drug will cause a decrease in refractory period.5-7 In individuals with reentrant paroxysmal supraventricular tachycardia this action is inconsequential, but in those with ventricular preexcitation accompanied by atrial fibrillation or flutter the effect may be catastrophic.

If inhibition in the atrioventricular node by ivabradine causes rate-dependent slowing of conduction and reduces ventricular rate during atrial fibrillation

Heart Rhythm ◽  
2014 ◽  
Vol 11 (12) ◽  
pp. 2288-2296 ◽  
Author(s):  
Richard L. Verrier ◽  
Rodolfo Bonatti ◽  
Ana F.G. Silva ◽  
Julio A.P. Batatinha ◽  
Bruce D. Nearing ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Atrioventricular Node ◽  
Ventricular Rate ◽  
Rate Dependent

Optimal ventricular rate slowing during atrial fibrillation by feedback AV nodal-selective vagal stimulation

2002 ◽  
Vol 282 (3) ◽  
pp. H1102-H1110 ◽  
Author(s):  
Youhua Zhang ◽  
Kent A. Mowrey ◽  
Shaowei Zhuang ◽  
Don W. Wallick ◽  
Zoran B. Popović ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Vagal Stimulation ◽  
Atrioventricular Node ◽  
Nerve Fibers ◽  
Ventricular Rate ◽  
Parasympathetic Nerve ◽  
Beneficial Effects ◽  
Sinus Cycle Length ◽  
Precise Relationship ◽  
Feedback Algorithm

Although the beneficial effects of ventricular rate (VR) slowing during atrial fibrillation (AF) are axiomatic, the precise relationship between VR and hemodynamics has not been determined. We hypothesized that selective atrioventricular node (AVN) vagal stimulation (AVN-VS) by varying the nerve stimulation intensity could achieve precise graded slowing and permit evaluation of an optimal VR during AF. The aims of the present study were the following: 1) to develop a method for computerized vagally controlled VR slowing during AF, 2) to determine the hemodynamic changes at each level of VR slowing, and 3) to establish the optimal anterograde VR during AF. AVN-VS was delivered to the epicardial fat pad that projects parasympathetic nerve fibers to the AVN in 14 dogs. Four target average VR levels, corresponding to 75%, 100%, 125%, and 150% of the sinus cycle length (SCL), were achieved by computer feedback algorithm. VR slowing resulted in improved hemodynamics and polynomial fit analysis found an optimum for the cardiac output at VR slowing of 87% SCL. We conclude that this novel method can be used to maintain slow anterograde conduction with best hemodynamics during AF.

Serum Digoxin Concentrations in Atrial Fibrillation: A Review

1982 ◽  
Vol 16 (7-8) ◽  
pp. 543-546 ◽  
Author(s):  
Joy E. Masuhara ◽  
Richard L. Lalonde
Keyword(s):  
Atrial Fibrillation ◽  
Atrioventricular Node ◽  
Signs And Symptoms ◽  
Ventricular Rate ◽  
Poor Correlation ◽  
Serum Digoxin ◽  
Great Relevance ◽  
The Many ◽  
Therapeutic Decision Making ◽  
Relationship Of

Studies evaluating the relationship of serum digoxin concentrations (SDCs) with pharmacodynamic effects in atrial fibrillation have important limitations. In general, a poor correlation is found between SDC and ventricular rate, but this is understandable, considering the many other factors that affect conduction through the atrioventricular node. The ventricular rate, although a clinically important and easily monitored parameter, may not always be a good measure of digoxin effect. In certain patients, signs and symptoms of toxicity may develop before the desired decrease in heart rate. The SDC may provide, in many cases, information that cannot be obtained solely from the clinical response, but is of great relevance to therapeutic decision making.

Selective AV nodal vagal stimulation improves hemodynamics during acute atrial fibrillation in dogs

2001 ◽  
Vol 281 (4) ◽  
pp. H1490-H1497 ◽  
Author(s):  
Don W. Wallick ◽  
Youhua Zhang ◽  
Tomotsugu Tabata ◽  
Shaowei Zhuang ◽  
Kent A. Mowrey ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Nerve Stimulation ◽  
Atrioventricular Node ◽  
Vital Role ◽  
Vagal Nerve ◽  
Vagal Nerve Stimulation ◽  
Ventricular Rate ◽  
Significant Deterioration ◽  
Vagal Nerves

Although the atrioventricular node (AVN) plays a vital role in blocking many of the atrial impulses from reaching the ventricles during atrial fibrillation (AF), a rapid irregular ventricular rate nevertheless persists. The goals of the present study were to explore the feasibility of novel epicardial selective vagal nerve stimulation for slowing of the ventricular rate during AF and to characterize the hemodynamic benefits in vivo. Electrophysiological-echocardiographic experiments were performed on 11 anesthetized open-chest dogs. Hemodynamic measurements were performed during three distinct periods: 1) sinus rate, 2) AF, and 3) AF with vagal nerve stimulation. AF was associated with significant deterioration of all measured parameters ( P < 0.025). The vagal nerve stimulation produced slowing of the ventricular rate, significant reversal of the pressure and contractile indexes ( P < 0.025), and a sharp reduction in one-half of the abortive ventricular contractions. The present study provides comprehensive evidence that slowing of the ventricular rate during AF by selective ganglionic stimulation of the vagal nerves that innervate the AVN successfully improved the hemodynamic responses.

Inhibition of If in the atrioventricular node as a mechanism for dronedarone’s reduction in ventricular rate during atrial fibrillation

Heart Rhythm ◽  
2013 ◽  
Vol 10 (11) ◽  
pp. 1692-1697 ◽  
Author(s):  
Richard L. Verrier ◽  
Marcel F. Sobrado ◽  
Vitor P.F. Pagotto ◽  
Alexandre F. Kanas ◽  
Ananda D. Machado ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Atrioventricular Node ◽  
Ventricular Rate

Autonomic modulation of ventricular rate in atrial fibrillation

1997 ◽  
Vol 272 (4) ◽  
pp. H1643-H1649 ◽  
Author(s):  
H. Nagayoshi ◽  
T. Janota ◽  
K. Hnatkova ◽  
A. J. Camm ◽  
M. Malik
Keyword(s):  
Atrial Fibrillation ◽  
Valsalva Maneuver ◽  
Atrioventricular Node ◽  
Persistent Atrial Fibrillation ◽  
Ventricular Rate ◽  
Autonomic Modulation ◽  
Moving Window ◽  
Postural Change ◽  
Respiration Rhythm ◽  
Ventricular Response

This study investigated the changes in R-R interval in 23 patients (11 men and 12 women; mean age 61 yr) with persistent atrial fibrillation in response to several provocative maneuvers including active postural change, Valsalva maneuver, handgrip, and rhythm-controlled respiration. Averaged R-R intervals were shortened immediately after postural change (from 797 +/- 35 ms supine to 677 +/- 27 ms standing; P < 0.01) and recovered to the 90% level within 100 s. During Valsalva strain and handgrip, mean R-R intervals were significantly shortened (from 737 +/- 37 ms sitting to 697 +/- 38 ms in Valsalva and from 773 +/- 68 ms sitting to 701 +/- 58 ms in handgrip; both P < 0.01). During rhythm-controlled respiration, only two cases (10.5%) showed power peaks in spectrograms of moving-window-averaged R-R intervals at the frequency corresponding to respiration rhythm. The ventricular response to atrial fibrillation is influenced by an increase in sympathetic tone and a decrease in parasympathetic tone but is not necessarily influenced by the increase in parasympathetic dominance. These results suggest that even in atrial fibrillation patients, the autonomic nervous system modulates the ventricular rate via the atrioventricular node and atrial tissue.

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