Right Atrial Mechanisms of Atrial Fibrillation in a Rat Model of Right Heart Disease

Hiram, Roddy; Naud, Patrice; Xiong, Feng; Al-U’datt, Doa’a G.F.; Algalarrondo, Vincent; Sirois, Martin G.; Tanguay, Jean‐François; Tardif, Jean‐Claude; Nattel, Stanley

doi:10.1016/j.jacc.2019.06.066

Cited by 81 publications

(101 citation statements)

References 31 publications

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“…In terms of electrical remodeling, we observed that SP rats exhibited abnormal prolongations in APD. APD prolongation was also observed in patients with lone paroxysmal AF, in the atrial tissue of patients predisposed to AF, and in various patient and animal studies of AF with underlying structural changes in the atria (28)(29).…”

Section: Discussionmentioning

confidence: 97%

TRPV4 blockade suppresses atrial fibrillation in sterile pericarditis rats

Liao¹,

Wu²,

Cheng³

et al. 2020

JCI Insight

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Atrial fibrillation (AF) commonly occurs after surgery and is associated with atrial remodeling. TRPV4 is functionally expressed in the heart, and its activation affects cardiac structure and functions. We hypothesized that TRPV4 blockade alleviates atrial remodeling and reduces AF induction in sterile pericarditis (SP) rats. TRPV4 antagonist GSK2193874 or vehicle was orally administered 1 d before pericardiotomy. AF susceptibility and atrial function were assessed using in vivo electrophysiology, ex vivo optical mapping, patch-clamp, and molecular biology on day 3 after surgery. TRPV4 expression increased in the atria of SP rats and patients with AF. GSK2193874 significantly reduced AF vulnerability in vivo and the frequency of atrial ectopy and AF with a reentrant pattern ex vivo. Mechanistically, GSK2193874 reversed the abnormal action potential duration (APD) prolongation in atrial myocytes through the regulation of voltage-gated K + currents (IK), reduced the activation of atrial fibroblasts by inhibiting P38, AKT, and STAT3 pathways, and alleviated the infiltration of immune cells. Our results reveal that TRPV4 blockade prevents abnormal changes in atrial myocyte electrophysiology and ameliorated atrial fibrosis and inflammation in SP rats, and, therefore, might be a promising strategy to treat AF, particularly post-operative AF.

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Section: Discussionmentioning

confidence: 97%

TRPV4 blockade suppresses atrial fibrillation in sterile pericarditis rats

Liao¹,

Wu²,

Cheng³

et al. 2020

JCI Insight

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“…Atrial brillation (AF) was induced with essentially the same protocol as described previously in detail [14]. In brief, rats were anesthetized with 1% sodium pentobarbital (30 mg/kg) through peritoneal injection.…”

Section: Methodsmentioning

confidence: 99%

Age-Related Changes in the Gut Microbiota Promote Atrial Fibrillation

Zhang¹,

Zhang²,

Luo³

et al. 2020

Preprint

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Background: Aging is the most significant contributor to the increasing prevalence of atrial fibrillation (AF). The gut microbiota dysbiosis is involved in age-associated diseases. However, whether age-associated gut microbial dysbiosis contributes to AF is still unknown. The aim of this study was to evaluate the effect of gut microbiota on the susceptibility of aging-induced AF and to elucidate the underlying mechanisms. Results: The gut microbiota profiling of fecal samples in aged (22-24 months old) and young (2-3 months old) rats was performed by 16S ribosomal RNA gene analysis. A rat model of fecal microbiota transplantation (FMT) was established for analyzing the possible role of age-associated gut microbial dysbiosis in AF. Here, we found that aging process led to marked shift of the microbiota spectrum. The microbiota in young rats following FMT resembled that of aged microbiota and transmitted the increased AF susceptibility by elevation of circulating lipopolysaccharide (LPS). The mechanism for LPS-driven atrial pro-arrhythmic action was dependent on the activation of atrial nucleotide binding and oligomerization domain-like receptor family pyrin domain-containing (NLRP3)-inflammasome. Inhibition of inflammasome by MCC950 resulted in lower atrial fibrosis and AF susceptibility. In addition, atrial fibrosis, plasma LPS concentration, plasma glucose to oral glucose tolerance test (OGTT), intestinal permeability, and gut pathology were significantly increased in elderly human subjects. Finally, altering the microbiota in aged recipient to resemble that of young restored the intestinal barrier dysfunction and LPS and impaired glucose tolerance, and the worse outcomes of aged dysbiosis on atrial fibrosis and AF susceptibility were abrogated. Conclusions: These data suggest that age-associated microbial dysbiosis induces circulating LPS and impairs glucose tolerance, and thereby promotes AF susceptibility through enhanced activity of atrial NLRP3-inflammasome.

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“…However, if the structural remodeling characterized by fibrosis and fatty infiltration are different between patients with RAF and those with left atrial fibrillation (LAF) remains unclear (Lendeckel and Wolke, 2018). Hiram et al (2019) showed the right atrial re-entrant activity involving right atrial fibrosis and conduction abnormalities produced a substrate for AF maintenance in a rat model. They provides the clues for the mechanism of AF in pulmonary hypertension or chronic obstructive pulmonary disease could be right atrial enlargement with substantial increase in atrial mass (Medi et al, 2011(Medi et al, , 2012.…”

Section: Right Atrial Fibrillation (Raf) and Right Atrialmentioning

confidence: 99%

“…So the right atrium should be an important part of the heart in atrial fibrillation process, and ablation only on the pulmonary vein would be non-responsive in the patients that excitation wavefronts and focal activity were on the right side from the beginning (Medi et al, 2011(Medi et al, , 2012Burnett and Kocheril, 2014;Hayashi et al, 2015;Hasebe et al, 2016Hasebe et al, , 2018Uemura, 2016;Gaeta et al, 2017;Wen et al, 2017;Vitarelli et al, 2018;Aksu et al, 2019;Hiram et al, 2019). However, few studies have assessed AF associated with LVRAS and dilated left and right atrium, the mechanism of RAF is still remaining unclear.…”

Section: Right Atrial Fibrillation (Raf) and Right Atrialmentioning

confidence: 99%

Higher Incidence of Atrial Fibrillation in Left Ventricular-to-Right Atrial Shunt Patients

et al. 2020

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Background: The possible association between atrial fibrillation (AF) and left ventricular-to-right atrial shunt (LVRAS) has never been reported yet. The present study investigated the incidence of AF in LVRAS.Methods: This was a retrospective study of consecutive patients undergoing echocardiography at a single tertiary center. Clinical data, laboratory results and echocardiography parameters such as right atrial area (RAA), right ventricular end diastolic diameter (RVDD) and left atrial diameter (LAD) were compared between LVRAS group and non-LVRAS patients, and between AF and non-AF patients. Propensity score matching was performed to decrease the effect of confounders. Logistic regression analysis and mediation analysis were used to estimate the relationship between LVRAS and AF.Results: A total of 3,436 patients were included, and the incidence of LVRAS was 1.16% (n = 40). The LVRAS group had significantly larger RAA, RVDD and LAD compared with non-LVRAS group. Those who suffered from AF showed larger RAA, RVDD and LAD compared with those who maintained sinus rhythm. Multivariable logistic regression showed that gender (OR: 0.608), age (OR: 1.048), LAD (OR: 1.111), mean pulmonary artery blood pressure (mPAP, OR: 1.023), TR (OR: 2.309) and LVRAS (OR: 12.217) were significant factors for AF. RAA could partially mediate the relationship between LVRAS and AF according to the result of mediation analysis.Conclusions: Our study suggested that LVRAS, TR, LAD, mPAP, age and male were risk factors for AF. RA enlargement might underlie mechanism in the higher incidence of AF in LVRAS patients. These findings should be confirmed in larger prospective studies.

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Right Atrial Mechanisms of Atrial Fibrillation in a Rat Model of Right Heart Disease

Cited by 81 publications

References 31 publications

TRPV4 blockade suppresses atrial fibrillation in sterile pericarditis rats

TRPV4 blockade suppresses atrial fibrillation in sterile pericarditis rats

Age-Related Changes in the Gut Microbiota Promote Atrial Fibrillation

Higher Incidence of Atrial Fibrillation in Left Ventricular-to-Right Atrial Shunt Patients

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