Faculty of Pharmacy, University of Montpellier, Montpellier, France; Université des Antilles, Guadeloupe, Pointe-à-Pitre, France; Montreal Heart Institute, Faculty of Medicine, University of Montreal, Montreal, Canada.
Department of Pharmacology and Therapeutics, McGill University, Canada.
J Hazard Mater. 2024 Oct 5;478:135533. doi: 10.1016/j.jhazmat.2024.135533. Epub 2024 Aug 14.
Chlordecone (CLD) is a carcinogenic organochlorine pesticide. CLD was shown to disturb the activity of cardiac Na-K-ATPase and Ca-Mg-ATPase. Conditions affecting these transmembrane pumps are often associated with cardiac arrhythmias (CA). However, little is known about the role of CLD on atrial fibrillation (AF) incidence, the most common type of CA.
Adult male Wistar rats (250 g-275 g) ingested daily-doses of CLD (0 μg/L, 0.1 μg/L, or 1 μg/L) diluted in their quotidian water for 4 weeks. From day (D)29 to D56, all rats received CLD-free water. Vulnerability to AF and cardiac function were evaluated at D28 and D56 by electrophysiological study, echocardiography, and optical-mapping. Levels of genes and proteins related to inflammation, fibrosis, and senescence were quantified by qPCR and immunoassays.
Twenty-eight days of CLD exposure were associated with significantly increased AF vulnerability compared to CLD-free rats. Contamination with 1 μg/L CLD significantly reduced atrial conduction velocity (ERP, APD). CLD-weaning normalized food consumption and weight intake. However, after the CLD-withdrawal period of 28 days, AF inducibility, atrial inflammation (IL6, IL1β), and atrial fibrosis (Masson's trichrome staining) remained significantly higher in rats exposed to 1 μg/L CLD compared to 0 μg/L.
Prolonged CLD ingestion provokes atrial conduction slowing and increased risk of AF. Although CLD-weaning, some persistent damages occurred in the atrium like atrial fibrosis and atrial senescence signals, which are accompanied by atrial inflammation and arrhythmogenicity.
氯丹（CLD）是一种致癌有机氯农药。CLD 被证明会干扰心肌 Na-K-ATP 酶和 Ca-Mg-ATP 酶的活性。影响这些跨膜泵的条件通常与心律失常（CA）有关。然而，关于 CLD 对心房颤动（AF）发病率的作用知之甚少，AF 是最常见的 CA 类型之一。
1）每日摄入 CLD 会引起致心律失常性心脏重构。2）CLD 戒断期可降低 CLD 诱导的 AF 易感性。
成年雄性 Wistar 大鼠（250-275g）每日口服 CLD（0μg/L、0.1μg/L 或 1μg/L），溶于日常饮用水中，连续 4 周。从第 29 天到第 56 天，所有大鼠均饮用不含 CLD 的水。在第 28 天和第 56 天，通过电生理研究、超声心动图和光学映射评估 AF 易感性和心功能。通过 qPCR 和免疫测定定量测定与炎症、纤维化和衰老相关的基因和蛋白水平。
与不含 CLD 的大鼠相比，暴露于 CLD 28 天与 AF 易感性显著增加相关。用 1μg/L CLD 污染显著降低心房传导速度（ERP、APD）。CLD 戒断后可恢复正常的饮食和体重摄入。然而，在 CLD 戒断 28 天后，与 0μg/L CLD 相比，暴露于 1μg/L CLD 的大鼠的 AF 易感性、心房炎症（IL6、IL1β）和心房纤维化（Masson 三色染色）仍然显著升高。
长期摄入 CLD 会导致心房传导速度减慢，AF 风险增加。尽管 CLD 戒断，但心房仍会发生一些持续的损伤，如心房纤维化和心房衰老信号，同时伴有心房炎症和致心律失常性。
