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Atrial Fibrillation (AF) is a common cardiac arrhythmia, often treated with Catheter Ablation (ABLA), involving cauterization of the left atrium (LA) to isolate arrhythmogenic areas. While studies suggest a lower prevalence in women, females with AF face a higher risk of severe complications. ABLA is associated with atrial inflammation, causing AF recurrence in about 10% of patients within 30 days and over 50% after 12 months. Patients experiencing AF recurrence post-ABLA show elevated levels of inflammatory markers. Colchicine is renowned for its anti-inflammatory and cardioprotective properties. Various clinical trials have yielded inconclusive results, with some indicating that Colchicine starting after the ABLA does not decrease AF recurrence. Exploring the sex-dependent response to preemptive Colchicine intervention before ABLA for treating potential ABLA-induced AF occurrence or recurrence. Male and female Wistar rats (225–275 g) were randomized into 4 groups: Sham or ABLA, treated or not with colchicine (1 mg/kg/day; intraperitoneally) starting 2 h before surgery. Sham animals underwent the surgery without ABLA. On days 1 (D1) and D3 post-ABLA, in vivo electrophysiological studies and echocardiography were performed. On D3, ex-vivo optical mapping was performed on Langendorff-perfused hearts, and atrial fibrosis, gene and protein expression were analyzed by Masson's trichrome staining, qPCR, and immunoblotting respectively. ABLA animals were significantly more susceptible to atrial arrhythmias compared to Sham. LA from ABLA rats have shown significantly slowed conduction velocity, increased fibrosis areas and inflammatory markers compared to Sham. Colchicine significantly reduced the incidence of AF post-ABLA, restored the normal P-wave duration, normalized LA conduction, LA fibrosis, and LA inflammation. Preliminary data revealed that female rats were less vulnerable to post-ABLA AF incidence than male. An effect accentuated by Colchicine treatment. Colchicine treatment starting before ABLA may reduce LA inflammation and AF incidence. A better understanding of male-female differences in the response to colchicine intervention could offer original insights into the management of post-ABLA AF incidence. [ABSTRACT FROM AUTHOR]

Atrial fibrillation (AF) is the most common form of cardiac arrhythmia. AF is associated with increased incidence of morbidity and mortality. AF risk factors include hypertension, obesity or right heart disease (RHD). Studies suggest a lower prevalence of AF in adult women compared to men, however, above 50 years old, females with AF have a greater vulnerability to severe complications such as stroke and sudden death. Inflammation has been described among contributors of AF. Our group recently described that inflammation-resolution may prevent AF in RHD, but the mechanism remains unclear. Interleukin-(IL)-37, an inhibitor of the IL1 family was shown to efficiently prevent IL18-induced inflammation. To target the IL1β-IL18 inflammatory axis in vivo and ex vivo the prevent atrial inflammation and AF vulnerability in RHD. IL37 prevents RHD-induced atrial inflammation and AF susceptibility. Pulmonary artery banding (PAB) was performed to induce right-sided cardiac hypertrophy and dilation in male and female Wistar rats (225–275 g). Sham animals did not receive the ligation. Animals were randomized into four groups: Sham and PAB treated or not with IL37 (100 ng/mL/kg). Cardiac echography and physiological studies were performed in vivo before sacrifices at day (D)0, D7, D14 and D21. Right atrial (RA) optical mapping was performed on Langendorff-perfused hearts to analyze the atrial conduction. Histology, western blot, and qPCR were performed to study the expression of proteins and genes involved in atrial inflammation, fibrosis, and electrical remodeling. Twenty-one days after surgery, PAB rats developed severe right-sided hypertrophy and dilation compared to Sham. PAB rats were more vulnerable to AF than Sham. Consistent with clinical evidence, female rats might be more resistant to AF than males. AF was associated with increased RA levels of inflammatory biomarkers including IL1β and IL6. IL37 treatment was associated with decreased atrial expression of inflammatory markers. IL37 is a potential new strategy promoting decreased atrial inflammation and AF prevention in RHD. [ABSTRACT FROM AUTHOR]

Atrial fibrillation (AF) is the most frequent arrhythmia observed in clinical practice. It affects approximately 1% of the population and has age, hypertension, obesity or myocardial infarction as risk factors. AF can lead to serious complications such as stroke and heart failure. AF therefore constitutes a major public health problem. Recently, a sarcomere-protein mutation was identified in the gene encoding an atrial-selective myosin light chain protein 4 (MYL-4) involved in cardiac contractility, causing a genetically inherited form of AF. Different signaling pathways have been implicated in causing these rhythm disorders, such as inflammation and atrial fibrosis. Conventional anti-inflammatory drugs are ineffective against AF. Bioactive endogenous autacoids, termed specialized pro-resolution mediators, including resolvin-D1 (RvD1), have been described to promote resolution of inflammation and potentially reduce the onset of AF. Elucidating how Resolvin D1 affects disturbed electrophysiological functions linked to the Myl-4 mutation. We developed a colony of male and female Sprague-Dawley Knock-In rats, mutated in the Myl-4 gene. A dose of 2 μg/kg/d of RvD1 (or equivalent dose of vehicle) was administered to wild-type (WT) and MYL-4 rats for 21 days. AF-susceptibility was assessed with in vivo electrophysiological study and conduction by optical mapping. The structure of the atria was studied by echocardiography, histology, and electron microscopy. The expression levels of proteins (by Western blot) and genes (by qPCR) involved in inflammation and cell apoptosis were assessed in the right and left atria of MYL-4 rats versus WT. RvD1 reduced AF inducibility in rats carrying the mutation compared to vehicle, while suppressing atrial inflammation (IL-1β), apoptosis-markers (Bax/Bcl2), and atrial structural remodeling (dilatation, hypertrophy). This project highlights the potential therapeutic effects of RvD1 treatment to prevent AF in atrial cardiomyopathies. [ABSTRACT FROM AUTHOR]

Ageing is designated among the main risk factors of atrial fibrillation (AF), the most common cardiac arrhythmia. It is estimated that 70% of AF patients are aged 65 and over. A particular Wistar-derived rat model of successful aging, the LOU/c/jall (LOU) rats, can live more than 35 months, equivalent to 100 years in humans, while the maximal lifespan of Wistar rats is around 22 months. Previous studies have shown that elderly Wistar rats are more vulnerable to AF than young congeners. In another hand, LOU rats have shown exceptional resistance to age-related diseases including neurodegenerative disorders, obesity, and hypertension. Very few data are available about the susceptibility of LOU rats to AF. Understand whether LOU rats' healthy aging is associated with resistance to AF. Male and female rats will be divided into five groups: LOU and Wistar rats of 5 months (young), 20 months (old), and 32 months (very old: LOU rats only). AF vulnerability and cardiac structure/function were evaluated in vivo by transesophageal electrophysiological study and echocardiography. Atrial conduction velocity was analyzed by ex vivo optical mapping. Immunohistochemistry, immunoblot analysis, and qPCR were used to investigate the levels of biomarkers involved in atrial inflammation and fibrosis. We observed increased atrial fibrosis in old Wistar rats compared to their younger counterparts. Old Wistar rats demonstrated a significantly higher incidence of AF compared to other groups. Echocardiography highlighted a more pronounced age-related atrial remodelling in 20-month-old Wistar rats compared to the other groups. Very old LOU rats exhibited normalized atrial fibrous content, maintained cardiac functions, and similar resistance to AF than young rats. Although these results were obtained from male animals, ongoing analyses are currently performed in females to determine whether differences related to biological sex are elucidated. Very old male LOU rats show significant resistance to AF compared to old Wistar rats. Our study suggests that LOU rats may carry innate cardioprotective properties probably limiting atrial fibrosis and inflammation to promote resistance to age-associated cardiac arrhythmias. [ABSTRACT FROM AUTHOR]