Abstract 15286: Prolonged Exposure to Pesticides and the Risk of Atrial Fibrillation: The Particular Case of Chlordecone

Abstract

Introduction: Atrial fibrillation (AF) is the most common form of cardiac arrhythmia. Chlordecone (CLD) is a pesticide known for its carcinogenic effects. Data suggest that CLD may disrupt the activity of myocardial Na + /K + -ATPase, deregulate mitochondrial Mg2+/ATPase in cardiomyocytes (CM), and inhibit CM Ca 2+ /ATPase. Little is known about the link between CLD and AF. Hypothesises: 1. Prolonged exposure to CLD induces arrhythmogenic cardiac remodeling in rats. 2.Cycle of CLD-withdrawal is accompanied by reduction of CLD-induced AF vulnerability. Methods: Male Wistar rats (250g) were exposed to CLD (0.1 μg/L or 1 μg/L) diluted in their daily water for 28 days. Control rats (CTRL) received water without CLD. Starting on day 29, all animals were exposed to CLD-free water. Electrophysiological study (EPS), echocardiography, and cardiac optical mapping (OM) were performed at days 28 and 56 to study cardiac function and atrial conduction. Expression levels of genes and proteins involved in inflammation, fibrosis and senescence were quantified by histology, immunoblot and qPCR. Results: At D28, all CLD-rats developed AF while CTRL rats did not. Compared to CTRL, weight up-take and water consumption were lower in animals exposed to CLD, although their food consumption was higher. Echocardiography revealed that CLD animals showed increased left ventricular contractility and atrial filling compared to CTRL. Acute CLD contamination caused a decrease in atrial conduction velocity and atrial action potential durations determined by cardiac OM ex-vivo . A 28-days CLD-withdrawal cycle was accompanied by weight normalization, and attenuation of AF inducibility, without improving atrial fibrosis and AF duration. CLD also decreased right and left atrial p21 mRNA expression, an effect not reversed by CLD weaning. Conclusion: CLD exposure is associated with increased AF vulnerability. CLD-weaning decreased (without abolishing), cardiac fibrosis and AF susceptibility.