title: TRPA1 mediates changes in heart rate variability and cardiac mechanical function in mice exposed to acrolein.
abstract: Short-term exposure to ambient air pollution is linked with adverse cardiovascular effects. While previous research focused primarily on particulate matter-induced responses, gaseous air pollutants also contribute to cause short-term cardiovascular effects. Mechanisms underlying such effects have not been adequately described, however the immediate nature of the response suggests involvement of irritant neural activation and downstream autonomic dysfunction. Thus, this study examines the role of TRPA1, an irritant sensory receptor found in the airways, in the cardiac response of mice to acrolein and ozone. Conscious unrestrained wild-type C57BL/6 (WT) and TRPA1 knockout (KO) mice implanted with radiotelemeters were exposed once to 3ppm acrolein, 0.3ppm ozone, or filtered air. Heart rate (HR) and electrocardiogram (ECG) were recorded continuously before, during and after exposure. Analysis of ECG morphology, incidence of arrhythmia and heart rate variability (HRV) were performed. Cardiac mechanical function was assessed using a Langendorff perfusion preparation 24h post-exposure. Acrolein exposure increased HRV independent of HR, as well as incidence of arrhythmia. Acrolein also increased left ventricular developed pressure in WT mice at 24h post-exposure. Ozone did not produce any changes in cardiac function. Neither gas produced ECG effects, changes in HRV, arrhythmogenesis, or mechanical function in KO mice. These data demonstrate that a single exposure to acrolein causes cardiac dysfunction through TRPA1 activation and autonomic imbalance characterized by a shift toward parasympathetic modulation. Furthermore, it is clear from the lack of ozone effects that although gaseous irritants are capable of eliciting immediate cardiac changes, gas concentration and properties play important roles.
authors.affiliation: Curriculum in Toxicology, School of Medicine, University of North Carolina, Chapel Hill, NC 27599, United States.
authors.forename: Nicole
authors.initials: N
authors.lastname: Kurhanewicz
authors.affiliation: Department of Environmental Sciences and Engineering, Gillings School of Global Public Health, University of North Carolina, Chapel Hill, NC 27599, United States.
authors.forename: Rachel
authors.initials: R
authors.lastname: McIntosh-Kastrinsky
authors.affiliation: Environmental Public Health Division, National Health and Environmental Effects Research Laboratory, US Environmental Protection Agency, Research Triangle Park, NC 27711, United States.
authors.forename: Haiyan
authors.initials: H
authors.lastname: Tong
authors.affiliation: Environmental Public Health Division, National Health and Environmental Effects Research Laboratory, US Environmental Protection Agency, Research Triangle Park, NC 27711, United States.
authors.forename: Allen
authors.initials: A
authors.lastname: Ledbetter
authors.affiliation: Environmental Public Health Division, National Health and Environmental Effects Research Laboratory, US Environmental Protection Agency, Research Triangle Park, NC 27711, United States.
authors.forename: Leon
authors.initials: L
authors.lastname: Walsh
authors.affiliation: Environmental Public Health Division, National Health and Environmental Effects Research Laboratory, US Environmental Protection Agency, Research Triangle Park, NC 27711, United States.
authors.forename: Aimen
authors.initials: A
authors.lastname: Farraj
authors.affiliation: Environmental Public Health Division, National Health and Environmental Effects Research Laboratory, US Environmental Protection Agency, Research Triangle Park, NC 27711, United States. Electronic address: hazari.mehdi@epa.gov.
authors.forename: Mehdi
authors.initials: M
authors.lastname: Hazari
mesh_terms: D000171:Acrolein / Q000008:administration & dosage / Q000633:toxicity*; D000818:Animals; D001145:Arrhythmias, Cardiac / Q000139:chemically induced* / Q000378:metabolism* / Q000503:physiopathology; D004562:Electrocardiography / Q000379:methods; D005260:Female; D006339:Heart Rate / Q000187:drug effects* / Q000502:physiology*; D019570:Inhalation Exposure / Q000009:adverse effects; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009924:Organ Culture Techniques; D000074025:TRPA1 Cation Channel; D013686:Telemetry / Q000379:methods; D050051:Transient Receptor Potential Channels / Q000502:physiology*
chemical_list: D000074025:TRPA1 Cation Channel; D050051:Transient Receptor Potential Channels; C475685:Trpa1 protein, mouse; D000171:Acrolein
keywords: Acrolein; Air pollution; Arrhythmia; Cardiac; Heart rate variability; TRPA1