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Aimen K. Farraj,¹ Najwa Haykal-Coates,¹ Darrell W. Winsett,¹ Mehdi S. Hazari,¹ Alex P. Carll,² William H. Rowan III,³ Allen D. Ledbetter,¹ Wayne E. Cascio,⁴ and Daniel L. Costa⁵

¹Experimental Toxicology Division, National Health and Environmental Effects Research Laboratory, U.S. Environmental Protection Agency, Research Triangle Park, North Carolina, USA; ²Environmental Sciences and Engineering, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA; ³ITT Corporation, Advanced Engineering and Sciences, Alexandria, Virginia, USA; ⁴Brody School of Medicine, East Carolina University, Greenville, North Carolina, USA; ⁵Office of Research and Development, U.S. Environmental Protection Agency, Research Triangle Park, North Carolina, USA

Abstract
Background: Exposure to combustion-derived fine particulate matter (PM) is associated with increased cardiovascular morbidity and mortality especially in individuals with cardiovascular disease, including hypertension. PM inhalation causes several adverse changes in cardiac function that are reflected in the electrocardiogram (ECG) , including altered cardiac rhythm, myocardial ischemia, and reduced heart rate variability (HRV) . The sensitivity and reliability of ECG-derived parameters as indicators of the cardiovascular toxicity of PM in rats are unclear.

Objective: We hypothesized that spontaneously hypertensive (SH) rats are more susceptible to the development of PM-induced arrhythmia, altered ECG morphology, and reduced HRV than are Wistar Kyoto (WKY) rats, a related strain with normal blood pressure.

Methods: We exposed rats once by nose-only inhalation for 4 hr to residual oil fly ash (ROFA) , an emission source particle rich in transition metals, or to air and then sacrificed them 1 or 48 hr later.

Results: ROFA-exposed SH rats developed nonconducted P-wave arrhythmias but no changes in ECG morphology or HRV. We found no ECG effects in ROFA-exposed WKY rats. ROFA-exposed SH rats also had greater pulmonary injury, neutrophil infiltration, and serum C-reactive protein than did ROFA-exposed WKY rats.

Conclusions: These results suggest that cardiac arrhythmias may be an early sensitive indicator of the propensity for PM inhalation to modify cardiovascular function.

Key words: arrhythmia, electrocardiogram, heart rate variability, hypertension, inhalation, nonconducted P-waves, particulate matter, rats, residual oil fly ash. Environ Health Perspect 117:709–715 (2009) . doi:10.1289/ehp.0800129 available via http://dx.doi.org/ [Online 31 December 2008]

Address correspondence to A.K. Farraj, U.S. Environmental Protection Agency, Experimental Toxicology Division, Mail Code B143-01, Research Triangle Park, NC 27711 USA. Telephone: (919) 541-5027. Fax: (919) 541-0034. E-mail: farraj.aimen@epa.gov

We thank A. Nyska of Tel Aviv University for histopathologic analysis of rat hearts, J. Richards for analysis of lavage fluid, and C. Gordon, J. Dye, G. Hatch, and M. Selgrade of the U.S. EPA for their review of the manuscript.

A.P.C. was supported by a U.S. EPA/University of North Carolina–Chapel Hill award (EPA CT82947101) .

The manuscript has been reviewed and approved for release by the National Health and Environmental Effects Research Laboratory, U.S. EPA. Approval does not signify that the contents necessarily reflect the views and policies of the U.S. EPA, nor does mention of trade names or commercial products constitute endorsement or recommendation for use.

W.H.R. is employed by the ITT Corporation, a for-profit company. The other authors declare they have no competing financial interests.

Received 27 August 2008 ; accepted 31 December 2008.