Development of a Substrate of Atrial Fibrillation During Chronic Atrioventricular Block in the Goat

Neuberger, Hans‐Ruprecht; Schotten, Ulrich; Verheule, Sander; Eijsbouts, Sabine; Blaauw, Yuri; Hunnik, Arne van; Allessie, Maurits A.

doi:10.1161/01.cir.0000151517.43137.97

Cited by 99 publications

(82 citation statements)

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“…21 The relevance of these findings to postoperative and permanent AF in humans was assessed in samples of the RA appendage from 130 patients undergoing cardiac surgery (26 with permanent AF, 32 who developed AF postoperatively, and 72 in normal SR before and after surgery), as were the effects of ex vivo atorvastatin on NADPH oxidase-derived atrial ROS production, biopterin levels, and NOS activity.…”

Section: Clinical Perspective On P 1117mentioning

confidence: 99%

Atrial Sources of Reactive Oxygen Species Vary With the Duration and Substrate of Atrial Fibrillation

et al. 2011

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Background-An altered nitric oxide-redox balance has been implicated in the pathogenesis of atrial fibrillation (AF).Statins inhibit NOX2-NADPH oxidases and prevent postoperative AF but are less effective in AF secondary prevention; the mechanisms underlying these findings are poorly understood. Methods and Results-By using goat models of pacing-induced AF or of atrial structural remodeling secondary to atrioventricular block and right atrial samples from 130 patients undergoing cardiac surgery, we found that the mechanisms responsible for the NO-redox imbalance differ between atria and with the duration and substrate of AF. Rac1 and NADPH oxidase activity and the protein level of NOX2 and p22phox were significantly increased in the left atrium of goats after 2 weeks of AF and in patients who developed postoperative AF in the absence of differences in leukocytes infiltration. Conversely, in the presence of longstanding AF or atrioventricular block, uncoupled nitric oxide synthase activity (secondary to reduced BH 4 content and/or increased arginase activity) and mitochondrial oxidases accounted for the biatrial increase in reactive oxygen species. Atorvastatin caused a mevalonate-reversible inhibition of Rac1 and NOX2-NADPH oxidase activity in right atrial samples from patients who developed postoperative AF, but it did not affect reactive oxygen species, nitric oxide synthase uncoupling, or BH 4 in patients with permanent AF. Key Words: atrial fibrillation Ⅲ free radicals Ⅲ nitric oxide synthase Ⅲ oxidative stress Ⅲ statins A trial fibrillation (AF), the most common sustained cardiac arrhythmia, is associated with significantly increased morbidity and mortality. 1 A striking feature of AF is its ability to sustain itself by inducing a number of electric and structural changes in the atrial myocardium, which in turn promote AF maintenance and increase vulnerability to relapse. 2 Although the process of AF-induced atrial remodeling and its role in begetting AF have been described in great detail in animal models of atrial tachyarrhythmia and in human AF, 2 the underlying mechanisms that result in these electric and structural changes remain unclear. Emerging data indicate that an altered nitric oxide (NO)-redox balance in the atrial myocardium may be implicated in the pathogenesis of AF and AF-induced atrial remodeling. In particular, in human and experimental atrial tachyarrhythmia, increased atrial production of reactive oxygen species (ROS) and reduced NO bioavailability are associated with atrial remodeling and increased vulnerability to AF, 3-7 both of which can be prevented by agents that decrease myocardial oxidative stress and inflammation. [7][8][9] In humans, NOX2-containing NADPH oxidases are the main source of ROS production in both right atrial (RA) homogenates and isolated myocytes, 6 and RA NADPH-stimulated superoxide production is independently associated with an increased risk of developing AF after cardiac surgery. 10 Statins prevent AF-induced early electric remodeling in dogs 9 and reduce the...

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Section: Clinical Perspective On P 1117mentioning

confidence: 99%

Atrial Sources of Reactive Oxygen Species Vary With the Duration and Substrate of Atrial Fibrillation

et al. 2011

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“…Chronic AVB and the resulting slow idioventricular rhythm in a goat can lead to progressive atrial dilatation. 29) Atrial dilatation is a predictor of recurrence of AF after catheter ablation. [23][24][25] However, because the slow idioventricular rhythm is prevented effectively by PM therapy in these patients, the effect of AVB on recurrence of AF need further studies.…”

Section: Discussionmentioning

confidence: 99%

Efficacy of Catheter Ablation for Atrial Fibrillation in Patients With a Permanent Pacemaker for Atrioventricular Block

Dong

Wang

et al. 2014

Int. Heart J.

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SummaryCatheter ablation has been established to be an effective therapy for drug-refractory paroxysmal AF and is recommended as the treatment of choice for many patients, including those with a permanent pacemaker (PM). However, the clinical efficacy of catheter ablation of paroxysmal AF in patients with a permanent PM for atrioventricular block (AVB) is not clear. Twenty-nine patients with a permanent PM for AVB (AVB + PM group), and 145 age-and gender-matched control patients (on a 1:5 basis) without AVB and without a permanent PM (no-AVB + no-PM group), were included in this study. Atrial fibrillation (AF) recurrence was defined as the occurrence of confirmed atrial tachyarrhythmia lasting more than 30 seconds beyond 3 months after catheter ablation in the absence of any antiarrhythmic treatment. During a mean follow-up period of 14.2 ± 8.6 months (range, 3-30 months), 54 patients (31.0%) developed recurrence of AF. The recurrence rate was higher in the AVB + PM group than in the no-AVB + no-PM group (48.3% versus 27.6%, P = 0.005). Cox regression analysis with adjustment for age, valvular heart disease, AVB and a PM together, left atrial (LA) diameter and PV isolation identified LA diameter (hazard ratio 1.054, 95% confidence interval 1.001-1.110, P = 0.047) and AVB and a PM together (hazard ratio 2.095, 95% confidence interval 1.109-3.960, P = 0.023) as two independent predictors of recurrence of AF. Patients with a permanent PM for AVB were at an increased risk of recurrence of AF after catheter ablation. (Int Heart J 2014; 55: 489-493) Key words: Recurrence A trial fibrillation (AF) is a common cardiac arrhythmia in the general population 1) and is associated with increased cardiovascular morbidity and mortality.2,3) A recent study showed that AF is the most frequent tachyarrhythmia in patients with a permanent pacemaker (PM), occurring in up to 37% of patients implanted due to atrioventricular block (AVB).4) Catheter ablation has been established to be an effective therapy for drug-refractory paroxysmal AF and is recommended as the treatment of choice for many patients, including those with a permanent PM. However, there is still a risk of recurrence after ablation. Our previous study evaluated the clinical efficacy of catheter ablation of paroxysmal AF in patients with a permanent PM for sick sinus syndrome (SSS) and showed that SSS and the use of a pacemaker together was an independent predictor of recurrence of AF. 5) SSS is primarily a disease of the elderly and is presumed to be due to senescence of the sinus node and atrial muscle. 6) Thus, SSS likely reflects an underlying atrial disease, which may be associated with an increased rate of recurrence of AF. In AVB patients with a permanent PM, although AVB may contribute little to the development of AF recurrence, the cumulative percentages of ventricular pacing may be higher in AVB patients than in SSS patients. Whether these patients also have an increased risk of recurrence of AF after catheter ablation is not clear. This retrospective study ...

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“…40) Membrane currents activated by hypotonicity 41) or stretch 42) have been reported to be present on the cell membrane in the pulmonary vein cardiomyocytes, and to play important roles in their automaticity. In chronic atrioventricular block goat and dog models, 43,44) atrial dilatation induced by chronic volume overload was shown to produce a substrate of atrial fibrillation. In the chronic atrioventricular block dog, the action potential of the pulmonary vein myocardium became significantly shorter while that of the left atria did not.…”

Section: Effect Of Pathophysiological Status and Humoral Factorsmentioning

confidence: 99%

Electrophysiological and Pharmacological Properties of the Pulmonary Vein Myocardium

Namekata

Tsuneoka

Tanaka

2013

Biological & Pharmaceutical Bulletin

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The pulmonary vein contains a myocardial layer extending from the left atrium, which is receiving attention as the source of ectopic electrical activity underlying atrial fibrillation. Electrophysiological and pharmacological analysis of the pulmonary vein myocardium performed in various experimental animal species have revealed characteristics such as presence of intracellular Ca 2+ oscillations and low repolarizing potency. The automaticity of the pulmonary vein myocardium is affected by various neurotransmitters, hormones and pharmacological agents. Clarification of the mechanisms and regulation of pulmonary vein automaticity would lead to the development of novel therapeutic strategies and pharmacological agents for atrial fibrillation.

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Development of a Substrate of Atrial Fibrillation During Chronic Atrioventricular Block in the Goat

Cited by 99 publications

References 44 publications

Atrial Sources of Reactive Oxygen Species Vary With the Duration and Substrate of Atrial Fibrillation

Atrial Sources of Reactive Oxygen Species Vary With the Duration and Substrate of Atrial Fibrillation

Efficacy of Catheter Ablation for Atrial Fibrillation in Patients With a Permanent Pacemaker for Atrioventricular Block

Electrophysiological and Pharmacological Properties of the Pulmonary Vein Myocardium

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