title: ST depression, arrhythmia, vagal dominance, and reduced cardiac micro-RNA in particulate-exposed rats.
abstract: Recently, investigators demonstrated associations between fine particulate matter (PM)-associated metals and adverse health effects. Residual oil fly ash (ROFA), a waste product of fossil fuel combustion from boilers, is rich in the transition metals Fe, Ni, and V, and when released as a fugitive particle, is an important contributor to ambient fine particulate air pollution. We hypothesized that a single-inhalation exposure to transition metal-rich PM will cause concentration-dependent cardiovascular toxicity in spontaneously hypertensive (SH) rats. Rats implanted with telemeters to monitor heart rate and electrocardiogram were exposed once by nose-only inhalation for 4 hours to 3.5 mg/m(3), 1.0 mg/m(3), or 0.45 mg/m(3) of a synthetic PM (dried salt solution), similar in composition to a well-studied ROFA sample consisting of Fe, Ni, and V. Exposure to the highest concentration of PM decreased T-wave amplitude and area, caused ST depression, reduced heart rate (HR), and increased nonconducted P-wave arrhythmias. These changes were accompanied by increased pulmonary inflammation, lung resistance, and vagal tone, as indicated by changes in markers of HR variability (increased root of the mean of squared differences of adjacent RR intervals [RMSSD], low frequency [LF], high frequency [HF], and decreased LF/HF), and attenuated myocardial micro-RNA (RNA segments that suppress translation by targeting messenger RNA) expression. The low and intermediate concentrations of PM had less effect on the inflammatory, HR variability, and micro-RNA endpoints, but still caused significant reductions in HR. In addition, the intermediate concentration caused ST depression and increased QRS area, whereas the low concentration increased the T-wave parameters. Thus, PM-induced cardiac dysfunction is mediated by multiple mechanisms that may be dependent on PM concentration and myocardial vulnerability (this abstract does not reflect the policy of the United States Environmental Protection Agency).
authors.affiliation: Environmental Public Health Division, United States Environmental Protection Agency, Research Triangle Park, NC 27711, USA. farraj.aimen@epa.gov
authors.forename: Aimen K
authors.initials: AK
authors.lastname: Farraj
authors.forename: Mehdi S
authors.initials: MS
authors.lastname: Hazari
authors.forename: Najwa
authors.initials: N
authors.lastname: Haykal-Coates
authors.forename: Christina
authors.initials: C
authors.lastname: Lamb
authors.forename: Darrell W
authors.initials: DW
authors.lastname: Winsett
authors.forename: Yue
authors.initials: Y
authors.lastname: Ge
authors.forename: Allen D
authors.initials: AD
authors.lastname: Ledbetter
authors.forename: Alex P
authors.initials: AP
authors.lastname: Carll
authors.forename: Maribel
authors.initials: M
authors.lastname: Bruno
authors.forename: Andy
authors.initials: A
authors.lastname: Ghio
authors.forename: Daniel L
authors.initials: DL
authors.lastname: Costa
mesh_terms: D000403:Airway Resistance / Q000187:drug effects; D000818:Animals; D001145:Arrhythmias, Cardiac / Q000209:etiology* / Q000235:genetics / Q000503:physiopathology; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000166:cytology; D002244:Carbon / Q000008:administration & dosage / Q000633:toxicity; D002319:Cardiovascular System / Q000187:drug effects* / Q000503:physiopathology*; D060729:Coal Ash; D018031:Connexin 43 / Q000378:metabolism; D004562:Electrocardiography; D006339:Heart Rate / Q000187:drug effects; D006352:Heart Ventricles / Q000187:drug effects / Q000378:metabolism; D018836:Inflammation Mediators / Q000097:blood; D008297:Male; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D052638:Particulate Matter / Q000008:administration & dosage / Q000633:toxicity*; D024661:Potassium Channels, Inwardly Rectifying / Q000378:metabolism; D051381:Rats; D011918:Rats, Inbred SHR; D013686:Telemetry; D028561:Transition Elements / Q000008:administration & dosage / Q000633:toxicity; D014630:Vagus Nerve / Q000187:drug effects* / Q000503:physiopathology*
chemical_list: D060729:Coal Ash; D018031:Connexin 43; D018836:Inflammation Mediators; C489461:Kir2.1 channel; D035683:MicroRNAs; D052638:Particulate Matter; D024661:Potassium Channels, Inwardly Rectifying; D028561:Transition Elements; D002244:Carbon