title: Overt and latent cardiac effects of ozone inhalation in rats: evidence for autonomic modulation and increased myocardial vulnerability.
abstract: BACKGROUND
  Ozone (O₃) is a well-documented respiratory oxidant, but increasing epidemiological evidence points to extrapulmonary effects, including positive associations between ambient O₃ concentrations and cardiovascular morbidity and mortality.
  
  
  OBJECTIVE
  With preliminary reports linking O₃ exposure with changes in heart rate (HR), we investigated the hypothesis that a single inhalation exposure to O₃ will cause concentration-dependent autonomic modulation of cardiac function in rats.
  
  
  METHODS
  Rats implanted with telemeters to monitor HR and cardiac electrophysiology [electrocardiography (ECG)] were exposed once by whole-body inhalation for 4 hr to 0.2 or 0.8 ppm O₃ or filtered air. A separate cohort was tested for vulnerability to aconitine-induced arrhythmia 24 hr after exposure.
  
  
  RESULTS
  Exposure to 0.8 ppm O₃ caused bradycardia, PR prolongation, ST depression, and substantial increases in atrial premature beats, sinoatrial block, and atrioventricular block, accompanied by concurrent increases in several HR variability parameters that were suggestive of increased parasympathetic tone. Low-O₃ exposure failed to elicit any overt changes in autonomic tone, heart rhythm, or ECG. However, both 0.2 and 0.8 ppm O₃ increased sensitivity to aconitine-induced arrhythmia formation, suggesting a latent O₃-induced alteration in myocardial excitability.
  
  
  CONCLUSIONS
  O₃ exposure causes several alterations in cardiac electrophysiology that are likely mediated by modulation of autonomic input to the heart. Moreover, exposure to low O₃ concentrations may cause subclinical effects that manifest only when triggered by a stressor, suggesting that the adverse health effects of ambient levels of air pollutants may be insidious and potentially underestimated.
authors.affiliation: Environmental Public Health Division, National Health and Environmental Effects Research Laboratory, U.S. Environmental Protection Agency, Research Triangle Park, North Carolina 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: Darrell W
authors.initials: DW
authors.lastname: Winsett
authors.forename: Anthony
authors.initials: A
authors.lastname: Kulukulualani
authors.forename: Alex P
authors.initials: AP
authors.lastname: Carll
authors.forename: Najwa
authors.initials: N
authors.lastname: Haykal-Coates
authors.forename: Christina M
authors.initials: CM
authors.lastname: Lamb
authors.forename: Edwin
authors.initials: E
authors.lastname: Lappi
authors.forename: Dock
authors.initials: D
authors.lastname: Terrell
authors.forename: Wayne E
authors.initials: WE
authors.lastname: Cascio
authors.forename: Daniel L
authors.initials: DL
authors.lastname: Costa
mesh_terms: D000157:Aconitine / Q000633:toxicity; D000818:Animals; D001145:Arrhythmias, Cardiac / Q000139:chemically induced / Q000503:physiopathology*; D001337:Autonomic Agents / Q000633:toxicity; D015331:Cohort Studies; D004305:Dose-Response Relationship, Drug; D004562:Electrocardiography; D006321:Heart / Q000187:drug effects* / Q000503:physiopathology; D006339:Heart Rate; D019570:Inhalation Exposure; D008297:Male; D010083:Oxidants, Photochemical / Q000633:toxicity*; D010126:Ozone / Q000633:toxicity*; D051381:Rats; D011918:Rats, Inbred SHR; D013686:Telemetry
chemical_list: D001337:Autonomic Agents; D010083:Oxidants, Photochemical; D010126:Ozone; D000157:Aconitine