title: Diesel Exhaust Worsens Cardiac Conduction Instability in Dobutamine-Challenged Wistar-Kyoto and Spontaneously Hypertensive Rats.
abstract: Short-term exposure to air pollution, particularly from vehicular sources, increases the risk of acute clinical cardiovascular events. However, cardiotoxicity is not always clearly discernible under ambient conditions; therefore, more subtle measures of cardiac dysfunction are necessary to elucidate the latent effects of exposure. Determine the effect of whole diesel exhaust (DE) exposure on reserve of refractoriness (RoR), an intrinsic electrophysiological measure of the heart's minimum level of refractoriness relative to development of electrical conduction instability, in rats undergoing exercise-like stress. Wistar-Kyoto (WKY) and spontaneously hypertensive (SH) rats implanted with radiotelemeters to continuously collect electrocardiogram (ECG) and heart rate were exposed to 150 µg/m3of DE and challenged with dobutamine 24 h later to mimic exercise-induced increases of the heart rate. The Chernyak-Starobin-Cohen (CSC) model was then applied to the ECG-derived QT and RR intervals collected during progressive increases in heart rate to calculate RoR for each rat. Filtered air-exposed WKY and SH rats did not have any decrease in RoR, which indicates increased risk of cardiac conduction instability; however, DE caused a significant decrease in both strains. Yet, the decrease in RoR in SH rats was eight times steeper when compared to WKY rats indicating greater cardiac conduction instability in the hypertensive strain. These data indicate that after exposure to DE, risk of cardiac instability increases during increasing stress, particularly in the presence of underlying cardiovascular disease. Furthermore, the CSC model, which was previously shown to reveal cardiac risk in humans, can be applied to rodent toxicology studies.
authors.affiliation: Environmental Public Health Division, National Health and Environmental Effects Research Laboratory, U.S. Environmental Protection Agency, 109 Alexander Drive, B105, Research Triangle Park, NC, 27711, USA. hazari.mehdi@epa.gov.
authors.forename: Mehdi S
authors.initials: MS
authors.lastname: Hazari
authors.affiliation: Department of Nanoscience, Joint School of Nanoscience and Nanoengineering, University of North Carolina at Greensboro, Greensboro, NC, 27401, USA.
authors.forename: Jarrett L
authors.initials: JL
authors.lastname: Lancaster
authors.affiliation: Department of Nanoscience, Joint School of Nanoscience and Nanoengineering, University of North Carolina at Greensboro, Greensboro, NC, 27401, USA.
authors.forename: Joseph M
authors.initials: JM
authors.lastname: Starobin
authors.affiliation: Environmental Public Health Division, National Health and Environmental Effects Research Laboratory, U.S. Environmental Protection Agency, 109 Alexander Drive, B105, Research Triangle Park, NC, 27711, USA.
authors.forename: Aimen K
authors.initials: AK
authors.lastname: Farraj
authors.affiliation: Environmental Public Health Division, National Health and Environmental Effects Research Laboratory, U.S. Environmental Protection Agency, 109 Alexander Drive, B105, Research Triangle Park, NC, 27711, USA.
authors.forename: Wayne E
authors.initials: WE
authors.lastname: Cascio
mesh_terms: D000200:Action Potentials; D058665:Adrenergic beta-1 Receptor Agonists; D000818:Animals; D001145:Arrhythmias, Cardiac / Q000139:chemically induced* / Q000503:physiopathology; D001794:Blood Pressure; D004195:Disease Models, Animal; D004280:Dobutamine; D004305:Dose-Response Relationship, Drug; D004562:Electrocardiography; D006329:Heart Conduction System / Q000187:drug effects* / Q000503:physiopathology; D006339:Heart Rate / Q000187:drug effects*; D006973:Hypertension / Q000150:complications* / Q000503:physiopathology; D019570:Inhalation Exposure / Q000009:adverse effects; D008297:Male; D008955:Models, Cardiovascular; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D018570:Risk Assessment; D012307:Risk Factors; D001335:Vehicle Emissions / Q000633:toxicity*
chemical_list: D058665:Adrenergic beta-1 Receptor Agonists; D001335:Vehicle Emissions; D004280:Dobutamine
keywords: Arrhythmia; Conduction instability; Diesel exhaust; Dobutamine; Reserve of refractoriness