Pollutants, including Organophosphorus and Organochloride Pesticides, May Increase the Risk of Cardiac Remodeling and Atrial Fibrillation: A Narrative Review

Abstract

Atrial fibrillation (AF) is the most common type of cardiac rhythm disorder. Recent clinical and experimental studies reveal that environmental pollutants, including organophosphorus-organochloride pesticides and air pollution, may contribute to the development of cardiac arrhythmias including AF. Here, we discussed the unifying cascade of events that may explain the role of pollutant exposure in the development of AF. Following ingestion and inhalation of pollution-promoting toxic compounds, damage-associated molecular pattern (DAMP) stimuli activate the inflammatory response and oxidative stress that may negatively affect the respiratory, cognitive, digestive, and cardiac systems. Although the detailed mechanisms underlying the association between pollutant exposure and the incidence of AF are not completely elucidated, some clinical reports and fundamental research data support the idea that pollutant poisoning can provoke perturbed ion channel function, myocardial electrical abnormalities, decreased action potential duration, slowed conduction, contractile dysfunction, cardiac fibrosis, and arrhythmias including AF.

Keywords: atrial fibrillation; cardiotoxicity; environmental pollution; pesticide.

Figure 1

Main sources of air pollutants. In general, air pollution is generated by either natural or anthropogenic emissions or a mix of both.

Figure 2

A list of primary and secondary pollutants. In general, air pollution is generated by either natural or anthropogenic emissions or a mix of both. CH₄: Methane; CO: Carbon Monoxide; NH₃: Ammoniac; NO₂: NMVOC: Non-Methane Volatile Organic Compounds; Nitrogen Dioxide; NOx: Nitrogen Oxides; O₃: Ozone; SO₂: Sulfur Dioxide; VOC: Volatile Organic Compounds.

Figure 3

Categories of Pesticides. Pesticides, including insecticides and herbicides, can be classified as natural and synthetic. Natural pesticides can be sub-categorized according to their origin as mineral oils or plant-based pesticides. Synthetic pesticides include organic and inorganic pesticides.

Figure 4

A list of the most popular Organochlorides and Organophosphorus. Organochlorides, including DDT, DDE, PCBs, and organophosphorus, including organophosphonates such as glyphosate, are among the most commonly used and commercialized pesticides worldwide. BHC: benzene hexachloride; DDT: dichlorodiphenyltrichloroethane; DDE: dichloro diphenyl dichloroethane; PCB: polychlorinated biphenyls.

Figure 5

Reported effects of chlordecone on the heart. Chlordecone poisoning has been associated with dysfunction of the myocardium, cardiomyocyte mitochondrial, and calcium-dependent contractility. ATPase: Adenosine Triphosphatase; Ca²⁺: Calcium; Cl: Chlordecone; Mg²⁺: Magnesium; Na⁺: Sodium; O: oxygen.

Figure 6

Possible mechanisms associating pesticide exposure to the development of atrial fibrillation. Ca²⁺: calcium; Cx43: connexin 43; I_Kur: ultra-rapid delayed rectifier outward potassium current; I_Na: inward sodium current; RyR2: ryanodine receptor; SERCA: sarco/endoplasmic reticulum Ca²⁺-ATPase.

Figure 7

A potential implication of the inflammatory response to pesticide poisoning, leading to atrial fibrillation. Pesticide poisoning provokes tissular injury following primary contact with skin, eyes, or digestive system. The toxic interaction leads to local injury and reaction provoking tissular damage signals impaired by DAMPs and PAMPs, which lead to the activation and the excretion of inflammatory signals that can affect other systems, via the blood circulation. Reported affected systems include, among others, the brain, the liver, the kidney, and the heart. Circulating pesticide metabolites and inflammatory signals may promote the amplification of cardiac inflammatory status, which, if unresolved can lead to chronic inflammation and cardiac fibrosis. Fibrosis is associated with abnormal conduction and atrial refractoriness, which contributes to increasing the risk of cardiac arrhythmias and atrial fibrillation. DAMPs: damage-associated molecular patterns; GSDMD: gasdermin-D; IL: interleukin; NFkB: nuclear factor kappa B; NLRP3: NACHT, LRR, and PYD domains-containing protein-3; Nt: N-terminal; P38 MAPK: p38 mitogen-activated protein kinases are a class of mitogen-activated protein kinase; PAMPs: pathogen-associated molecular patterns; PMN: polymorphonuclear neutrophils; TGF-b: transforming growth factor beta; TNF-a: tumor necrosis factor-alpha.

Figure 8

A proposed algorithm for AF-patient management following pollutant poisoning. AF: atrial fibrillation; NT-proBNP: N-terminal pro-brain natriuretic peptide; IL: interleukin; WHO: World Health Organization.