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
Article

Abstract

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.

Keywords

Diesel exhaust Arrhythmia Conduction instability Reserve of refractoriness Dobutamine 

Abbreviations

APD

Action potential duration

DE

Diesel exhaust

DI

Diastolic interval

ECG

Electrocardiogram

ERP

Effective refractory period

HR

Heart rate

RoR

Reserve of refractoriness

SH

Spontaneously hypertensive

WKY

Wistar–Kyoto

Notes

Acknowledgments

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.

References

  1. 1.
    Allen, J., Trenga, C. A., Peretz, A., Sullivan, J. H., Carlsten, C. C., & Kaufman, J. D. (2009). Effect of diesel exhaust inhalation on antioxidant and oxidative stress responses in adults with metabolic syndrome. Inhalation Toxicology, 21(13), 1061–1067.CrossRefPubMedPubMedCentralGoogle Scholar
  2. 2.
    Antzelevitch, C., Sicouri, S., Litovsky, S. H., Lukas, A., Krishnan, S. C., Didiego, J. M., et al. (1991). Heterogeneity within the ventricular wall: Electrophysiology and pharmacology of epicardial, endocardial and M-cells. Circulation Research, 69, 1427–1449.CrossRefPubMedGoogle Scholar
  3. 3.
    Balakumar, P., Singh, H., Singh, M., & Anand-Srivastava, M. B. (2009). The impairment of preconditioning-mediated cardioprotection in pathological conditions. Pharmacological Research, 60, 18–23.CrossRefPubMedGoogle Scholar
  4. 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
  5. 5.
    Brook, R. D. (2008). Cardiovascular effects of air pollution. Clinical Science, 115, 175–187.CrossRefPubMedGoogle Scholar
  6. 6.
    Chernyak, Y. B., Starobin, J. M., & Cohen, R. J. (1998). Class of exactly solvable models of excitable media. Physical Review Letters, 80, 5675–5678.CrossRefGoogle Scholar
  7. 7.
    Fitzhugh, R. (1961). Impulses and physiological states in theoretical models of nerve membrane. Biophysical Journal, 1(6), 445–466.CrossRefPubMedPubMedCentralGoogle Scholar
  8. 8.
    Hool, L. C., & Corry, B. (2007). Redox control of calcium channels: From mechanisms to therapeutic opportunities. Antioxidants & Redox Signaling, 9(4), 409–435.CrossRefGoogle Scholar
  9. 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
  10. 10.
    Goldberg, M. S., Burnett, R. T., Stieb, D. M., Brophy, J. M., Daskalopoulou, S. S., Valois, M. F., et al. (2013). Associations between ambient air pollution and daily mortality among elderly persons in Montreal, Quebec. Science Total Environmental, 463–464, 931–942.CrossRefGoogle Scholar
  11. 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
  12. 12.
    Hoek, G., Krishnan, R. M., Beelen, R., Peters, A., Ostro, B., Brunekreef, B., & Kaufman, J. D. (2013). Long-term air pollution exposure and cardio-respiratory mortality: A review. Environmental Health, 12(1), 43–52.CrossRefPubMedPubMedCentralGoogle Scholar
  13. 13.
    Kolbe, K., Schönherr, R., Gessner, G., Sahoo, N., Hoshi, T., & Heinemann, S. H. (2010). Cysteine 723 in the C-linker segment confers oxidative inhibition of hERG1 potassium channels. Journal of Physiology, 588, 2999–3009.CrossRefPubMedPubMedCentralGoogle Scholar
  14. 14.
    Langrish, J. P., Watts, S. J., Hunter, A. J., Shah, A. S., Bosson, J. A., Unosson, J., et al. (2014). Controlled exposures to air pollution and risk of cardiac arrhythmia. Environmental Health Perspectives, 122(7), 747–753.PubMedPubMedCentralGoogle Scholar
  15. 15.
    Lauer, M. S., Pothier, C. E., Chernyak, Y. B., Brunken, R., Lieber, M., Apperson-Hanson, C., et al. (2006). Exercise-induced QT/RR-interval hysteresis as a predictor of myocardial ischemia. Journal of Electrocardiology, 39(3), 315–323.CrossRefPubMedGoogle Scholar
  16. 16.
    Madden, M. C., Stevens, T., Case, M., Schmitt, M., Diaz-Sanchez, D., Bassett, M., et al. (2014). Diesel exhaust modulates ozone-induced lung function decrements in healthy human volunteers. Particle and Fibre Toxicology, 11(1), 37.CrossRefPubMedPubMedCentralGoogle Scholar
  17. 17.
    Miller, M. R., Shaw, C. A., & Langrish, J. P. (2012). From particles to patients: Oxidative stress and the cardiovascular effects of air pollution. Future Cardiology, 8(4), 577–602.CrossRefPubMedGoogle Scholar
  18. 18.
    Mills, N. L., Tornqvist, H., Gonzalez, M. C., Vink, E., Robinson, S. D., Soderberg, S., et al. (2007). Ischemic and thrombotic effects of dilute diesel-exhaust inhalation in men with coronary heart disease. New England Journal of Medicine, 357(111), 1075–1082.CrossRefPubMedGoogle Scholar
  19. 19.
    Pechánová, O., Zicha, J., Paulis, L., et al. (2007). The effect of N-acetylcysteine and melatonin in adult spontaneously hypertensive rats with established hypertension. European Journal of Pharmacology, 561, 129–136.CrossRefPubMedGoogle Scholar
  20. 20.
    Ravingerová, T., Slezák, J., Tribulová, J., Džurba, A., Uhrík, B., & Ziegelhoffer, A. (1999). Reactive oxygen species contribute to high incidence of reperfusion-induced arrhythmias in isolated rat heart. Life Sciences, 18(19), 1927–1931.CrossRefGoogle Scholar
  21. 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
  22. 22.
    Rhoden, C. R., Wellenius, G. A., Ghelfi, E., Lawrence, J., & Gonzalez-Flecha, B. (2005). PM-induced cardiac oxidative stress and dysfunction are mediated by autonomic stimulation. Biochimica et Biophysica Acta, 1725, 305–313.CrossRefPubMedGoogle Scholar
  23. 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
  24. 24.
    Vassallo, J. A., Cassidy, D. M., Kindwall, K. E., Marchlinski, F. E., & Josephson, M. E. (1988). Nonuniform recovery of excitability in the left ventricle. Circulation, 78, 1365–1371.CrossRefPubMedGoogle Scholar
  25. 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. 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

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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