Diesel Exhaust Worsens Cardiac Conduction Instability in Dobutamine-Challenged Wistar–Kyoto and Spontaneously Hypertensive Rats
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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.
KeywordsDiesel exhaust Arrhythmia Conduction instability Reserve of refractoriness Dobutamine
Action potential duration
Effective refractory period
Reserve of refractoriness
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.
- 4.Barath, S., Mills, N. L., Adelroth, E., Olin, A. C., & Blomberg, A. (2013). Diesel exhaust but not ozone increases fraction of exhaled nitric oxide in a randomized controlled experimental exposure study of healthy human subjects. Environmental Health, 12, 36.CrossRefPubMedPubMedCentralGoogle Scholar
- 9.Idriss, S. F., Neu, W. K., Varadarajan, V., Antonijevic, T., Gilani, S. S., & Starobin, J. M. (2012). Feasibility of non-invasive determination of the stability of propagation reserve in patients. Computing in Cardiology, 39, 353–356.Google Scholar
- 11.Hazari, M. S., Callaway, J., Winsett, D. W., Lamb, C., Haykal-Coates, N., Krantz, Q. T., et al. (2012). Dobutamine “stress” test and latent cardiac susceptibility to inhaled diesel exhaust in normal and hypertensive rats. Environmental Health Perspectives, 120(8), 1088–1093.CrossRefPubMedPubMedCentralGoogle Scholar
- 21.Ravingerova, T., Bernatova, I., Matejikova, J., Ledvenyiova, V., Nemcekova, M., Pechanova, O., et al. (2011). Impaired cardiac ischemic tolerance in spontaneously hypertensive rats is attenuated by adaptation to chronic and acute stress. Experimental & Clinical Cardiology, 16(3), 23–29.Google Scholar
- 23.Tong, H., Rappold, A. G., Caughey, M., Hinderliter, A. L., Graff, D. W., Bernsten, J. H., et al. (2014). Cardiovascular effects caused by increasing concentrations of diesel exhaust in middle-aged healthy GSTM1 null human volunteers. Inhalation Toxicology, 26(6), 319–326.CrossRefPubMedGoogle Scholar
- 25.Wolk, R., Cobbe, S. M., Hicks, M. N., & Kane, K. A. (1999). Functional, structural, and dynamic basis of electrical heterogeneity in health and diseased cardiac muscle: Implications for arrhythmogenesis and anti-arrhythmic drug therapy. Pharmacology & Therapeutics, 84, 207–231.CrossRefGoogle Scholar
- 26.Zhang, Y., Xiao, J., Wang, H., Luo, X., Wang, J., Villeneuve, L. R., et al. (2006). Restoring depressed HERG K + channel function as a mechanism for insulin treatment of abnormal QT prolongation and associated arrhythmias in diabetic rabbits. American Journal of Physiology Heart and Circulatory Physiology, 291, H1446–H1455.CrossRefPubMedGoogle Scholar