Global Air Pollutant Phenanthrene and Arrhythmic Outcomes in a Mouse Model

Overview

Journal Environ Health Perspect

Date 2023 Nov 1

PMID 37909723

Authors

Sana Yaar

Tatiana S Filatova

Ellie England

Shiva N Kompella

Jules C Hancox

David A Bechtold

Luigi Venetucci

Denis V Abramochkin

Holly A Shiels

Affiliations

Soon will be listed here.

Abstract

Background: The three-ringed polycyclic aromatic hydrocarbon (PAH) phenanthrene (Phe) has been implicated in the cardiotoxicity of petroleum-based pollution in aquatic systems, where it disrupts the contractile and electrical function of the fish heart. Phe is also found adsorbed to particulate matter and in the gas phase of air pollution, but to date, no studies have investigated the impact of Phe on mammalian cardiac function.

Objectives: Our objectives were to determine the arrhythmogenic potential of acute Phe exposure on mammalian cardiac function and define the underlying mechanisms to provide insight into the toxicity risk to humans.

Methods: Langendorff-perfused mouse hearts were used to test the arrhythmogenic potential of Phe on myocardial function, and voltage- and current-clamp recordings were used to define underlying cellular mechanisms in isolated cardiomyocytes.

Results: Mouse hearts exposed to Phe for 15-min exhibited a significantly slower heart rate (, hearts), a prolonged PR interval (, hearts), and a slower conduction velocity (, hearts). Whole-cell recordings from isolated cardiomyocytes revealed action potential (AP) duration prolongation (at 80% repolarization; , cells) and inhibition of key murine repolarizing currents-transient outward potassium current () and ultrarapid potassium current ()-following Phe exposure. A significant reduction in AP upstroke velocity (, cells) and inhibition of the fast sodium current (; , cells) and calcium current (; ) were also observed, explaining the slowed conduction velocity in intact hearts. Finally, acute exposure to Phe significantly increased susceptibility to arrhythmias (, hearts).

Discussion: To the best of our knowledge, this is the first evidence of direct inhibitory effects of Phe on mammalian cardiac electrical activity at both the whole-heart and cell levels. This electrical dysfunction manifested as an increase in arrhythmia susceptibility due to impairment of both conduction and repolarization. Similar effects in humans could have serious health consequences, warranting greater regulatory attention and toxicological investigation into this ubiquitous PAH pollutant generated from fossil-fuel combustion. https://doi.org/10.1289/EHP12775.

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