Cardiovascular Toxicology

, Volume 17, Issue 2, pp 120–129 | Cite as

Diesel Exhaust Worsens Cardiac Conduction Instability in Dobutamine-Challenged Wistar–Kyoto and Spontaneously Hypertensive Rats

  • Mehdi S. Hazari
  • Jarrett L. Lancaster
  • Joseph M. Starobin
  • Aimen K. Farraj
  • Wayne E. Cascio


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/m3 of 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.


Diesel exhaust Arrhythmia Conduction instability Reserve of refractoriness Dobutamine 



Action potential duration


Diesel exhaust


Diastolic interval




Effective refractory period


Heart rate


Reserve of refractoriness


Spontaneously hypertensive





We would like to thank Drs. Janice Dye, Leslie Thompson, Ian Gilmour, Wayne Cascio and Ronald Hines for their insightful review of the manuscript.

Compliance with Ethical Standards

Conflict of interest

The authors do not have any actual or potential competing financial interests.


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Copyright information

© Springer Science+Business Media New York (outside the USA) 2016

Authors and Affiliations

  • Mehdi S. Hazari
    • 1
  • Jarrett L. Lancaster
    • 2
  • Joseph M. Starobin
    • 2
  • Aimen K. Farraj
    • 1
  • Wayne E. Cascio
    • 1
  1. 1.Environmental Public Health Division, National Health and Environmental Effects Research LaboratoryU.S. Environmental Protection AgencyResearch Triangle ParkUSA
  2. 2.Department of Nanoscience, Joint School of Nanoscience and NanoengineeringUniversity of North Carolina at GreensboroGreensboroUSA

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