Cardiovascular Toxicology

, Volume 18, Issue 6, pp 507–519 | Cite as

The Acute Effects of Age and Particulate Matter Exposure on Heart Rate and Heart Rate Variability in Mice

  • Blake A. BennettEmail author
  • Ernst W. Spannhake
  • Ana M. Rule
  • Patrick N. Breysse
  • Clarke G. Tankersley


Exposure to ambient particulate matter (PM) is associated with increased cardiac morbidity and mortality with the elderly considered to be the most susceptible. The purpose of this study was to determine if exposure to PM would cause a greater impact on heart regulation in older DBA/2 (D2) male mice as determined by changes in heart rate (HR) and heart rate variability (HRV). D2 mice at the ages of 4, 12, and 19 months were instilled with 100 µg of PM or saline by aspiration. Before and after the aspiration, 3-min echocardiogram (ECG) samples for HR and HRV were recorded at 15-min intervals for 3 h along with corresponding measurements of homeostasis, such as temperature, metabolism, and ventilation. PM exposure resulted in an increase in HRV, declines in HR, and altered measures of homeostasis for a subset of the 12-mo mice. The PM aspiration did not affect cardiac or homeostasis parameters in the 4- or 19-mo mice. Our results suggest that a select group of middle-age mice are more susceptible to alterations in their heart rhythm after PM exposure and highlight that there are acute age-related differences in heart rhythm following PM exposure.


Aging Susceptible populations Particulate matter Heart rate variability Cardiac Mouse 



We thank R. Shinohara of University of Pennsylvania, Department of Biostatistics and Epidemiology for statistical support. From Johns Hopkins University, Bloomberg School of Public Health, Department of Environmental Health Science, we would like to thank R. Rabold for his assistance with the telemetry surgeries, H. Lee for helping with the experiments, and J. Mihalic for measuring the particulate matter composition.


The study was funded by the National Institutes of Health, National Heart, Lung, and Blood Institute (T32 HL007534); National Institutes of Health, National Institute on Aging (R01 AG021057); and the Environmental Protection Agency (RD-83241701).

Compliance with Ethical Standards

Conflict of interest

All authors declare that they have no conflict of interest.


  1. 1.
    Peng, R. D., Chang, H. H., Bell, M. L., McDermott, A., Zeger, S. L., Samet, J. M., & Dominici, F. (2008). Coarse particulate matter air pollution and hospital admissions for cardiovascular and respiratory diseases among Medicare patients. JAMA, 299, 2172–2179.CrossRefPubMedPubMedCentralGoogle Scholar
  2. 2.
    Zanobetti, A., & Schwartz, J. (2009). The effect of fine and coarse particulate air pollution on mortality: A national analysis. Environmental Health Perspectives, 117, 898–903.CrossRefPubMedPubMedCentralGoogle Scholar
  3. 3.
    Dominici, F., Peng, R. D., Bell, M. L., Pham, L., McDermott, A., Zeger, S. L., & Samet, J. M. (2006). Fine particulate air pollution and hospital admission for cardiovascular and respiratory diseases. JAMA, 295, 1127–1134.CrossRefPubMedPubMedCentralGoogle Scholar
  4. 4.
    Brook, R. D., Rajagopalan, S., Pope, C. A., Brook, J. R., Bhatnagar, A., Diez-Roux, A. V., Holguin, F., Hong, Y., Luepker, R. V., Mittleman, M. A., Peters, A., Siscovick, D., Smith, S. C., Whitsel, L., & Kaufman, J. D. (2010). Particulate matter air pollution and cardiovascular disease: An update to the scientific statement from the American Heart Association. Circulation, 121, 2331–2378.CrossRefPubMedGoogle Scholar
  5. 5.
    Task Force. (1996). Heart rate variability: Standards of measurement, physiological interpretation and clinical use. Task Force of the European Society of Cardiology and the North American Society of Pacing and Electrophysiology. Circulation, 93, 1043–1065.CrossRefGoogle Scholar
  6. 6.
    Bilchick, K. C., Fetics, B., Djoukeng, R., Fisher, S. G., Fletcher, R. D., Singh, S. N., Nevo, E., & Berger, R. D. (2002). Prognostic value of heart rate variability in chronic congestive heart failure (Veterans Affairs’ Survival Trial of Antiarrhythmic Therapy in Congestive Heart Failure). American Journal of Cardiology, 90, 24–28.CrossRefPubMedGoogle Scholar
  7. 7.
    Tsuji, H., Venditti, F. J., Manders, E. S., Evans, J. C., Larson, M. G., Feldman, C. L., & Levy, D. (1994). Reduced heart rate variability and mortality risk in an elderly cohort. The Framingham Heart Study. Circulation, 90, 878–883.CrossRefPubMedGoogle Scholar
  8. 8.
    Zeka, A., Zanobetti, A., & Schwartz, J. (2006). Individual-level modifiers of the effects of particulate matter on daily mortality. American Journal of Epidemiology, 163, 849–859.CrossRefPubMedGoogle Scholar
  9. 9.
    Adar, S. D., Gold, D. R., Coull, B. A., Schwartz, J., Stone, P. H., & Suh, H. (2007). Focused exposures to airborne traffic particles and heart rate variability in the elderly. Epidemiology, 18, 95–103.CrossRefPubMedGoogle Scholar
  10. 10.
    Pope, C. A., Hansen, M. L., Long, R. W., Nielsen, K. R., Eatough, N. L., Wilson, W. E., & Eatough, D. J. (2004). Ambient particulate air pollution, heart rate variability, and blood markers of inflammation in a panel of elderly subjects. Environmental Health Perspectives, 112, 339–345.CrossRefPubMedPubMedCentralGoogle Scholar
  11. 11.
    Sullivan, J. H., Schreuder, A. B., Trenga, C. A., Liu, S. L., Larson, T. V., Koenig, J. Q., & Kaufman, J. D. (2005). Association between short term exposure to fine particulate matter and heart rate variability in older subjects with and without heart disease. Thorax, 60, 462–466.CrossRefPubMedPubMedCentralGoogle Scholar
  12. 12.
    Hamade, A. K., & Tankersley, C. G. (2009). Interstrain variation in cardiac and respiratory adaptation to repeated ozone and particulate matter exposures. American Journal of Physiology-Regulatory, Integrative and Comparative Physiology, 296, R1202–R1215.CrossRefPubMedPubMedCentralGoogle Scholar
  13. 13.
    Ramos-Bonilla, J. P., Breysse, P. N., Dominici, F., Geyh, A., & Tankersley, C. G. (2010). Ambient air pollution alters heart rate regulation in aged mice. Inhalation Toxicology, 22, 330–339.CrossRefPubMedGoogle Scholar
  14. 14.
    Tankersley, C. G., Campen, M., Bierman, A., Flanders, S. E., Broman, K. W., & Rabold, R. (2004). Particle effects on heart-rate regulation in senescent mice. Inhalation Toxicology, 16, 381–390.CrossRefPubMedGoogle Scholar
  15. 15.
    Calvi, C. L., Podowski, M., D’Alessio, F. R., Metzger, S. L., Misono, K., Poonyagariyagorn, H., Lopez-Mercado, A., Ku, T., Lauer, T., Cheadle, C., Talbot, C. C., Jie, C., McGrath-Morrow, S., King, L. S., Walston, J., & Neptune, E. R. (2011). Critical transition in tissue homeostasis accompanies murine lung senescence. PLoS ONE, 6, e20712.CrossRefPubMedPubMedCentralGoogle Scholar
  16. 16.
    Flurkey, K., Currer, J. M., & Harrison, D. E. (2007). Mouse Models in Aging Research. In J. G. Fox, M. T. Davisson, F. W. Quimby, S. W. Barthold, C. E. Newcomer & A. L. Smith (Eds.), The mouse in biomedical (pp. 637–672). Burlington, MA: Research American College of Laboratory Animal Medicine.CrossRefGoogle Scholar
  17. 17.
    Tankersley, C. G., Irizarry, R., Flanders, S. E., Rabold, R., & Frank, R. (2003). Unstable heart rate and temperature regulation predict mortality in AKR/J mice. American Journal of Physiology-Regulatory, Integrative and Comparative Physiology, 284, R742-750.CrossRefGoogle Scholar
  18. 18.
    Rule, A. M., Geyh, A. S., Ramos-Bonilla, J. P., Mihalic, J. N., Margulies, J. D., Polyak, L. M., Kesavan, J., & Breysse, P. N. (2010). Design and characterization of a sequential cyclone system for the collection of bulk particulate matter. Journal of Environmental Monitoring, 12, 1807–1814.CrossRefPubMedGoogle Scholar
  19. 19.
    Han, I., Mihalic, J. N., Ramos-Bonilla, J. P., Rule, A. M., Polyak, L. M., Peng, R. D., Geyh, A. S., & Breysse, P. N. (2012). Assessment of heterogeneity of metal composition of fine particulate matter collected from eight US counties using principal component analysis. Journal of the Air & Waste Management Association, 62, 773–782.CrossRefGoogle Scholar
  20. 20.
    Sokal, R. S., Rohlf, F. J. (1995). Biometry. New York: W. H. Freeman and Company.Google Scholar
  21. 21.
    Ramsay, J. O., & Silverman, B. W. (2005). Functional data analysis. New York: Springer.CrossRefGoogle Scholar
  22. 22.
    Campen, M. J., Nolan, J. P., Schladweiler, M. C., Kodavanti, U. P., Costa, D. L., & Watkinson, W. P. (2002). Cardiac and thermoregulatory effects of instilled particulate matter-associated transition metals in healthy and cardiopulmonary-compromised rats. Journal of Toxicology and Environmental Health, Part A, 65, 1615–1631.CrossRefGoogle Scholar
  23. 23.
    Farraj, A. K., Hazari, M. S., Haykal-Coates, N., Lamb, C., Winsett, D. W., Ge, Y., Ledbetter, A. D., Carll, A. P., Bruno, M., Ghio, A., & Costa, D. L. (2011). ST depression, arrhythmia, vagal dominance, and reduced cardiac micro-RNA in particulate-exposed rats. American Journal of Respiratory Cell and Molecular Biology, 44, 185–196.CrossRefPubMedGoogle Scholar
  24. 24.
    Coleridge, H. M., & Coleridge, J. C. (1994). Pulmonary reflexes: Neural mechanisms of pulmonary defense. Annual Review of Physiology, 56, 69–91.CrossRefPubMedGoogle Scholar
  25. 25.
    Widdicombe, J., & Lee, L. Y. (2001). Airway reflexes, autonomic function, and cardiovascular responses. Environmental Health Perspectives, 109(Suppl 4), 579–584.CrossRefPubMedPubMedCentralGoogle Scholar
  26. 26.
    Perez, C. M., Hazari, M. S., & Farraj, A. K. (2015). Role of autonomic reflex arcs in cardiovascular responses to air pollution exposure. Cardiovascular Toxicology, 15(1), 69–78.CrossRefPubMedPubMedCentralGoogle Scholar
  27. 27.
    Campen, M. J., Nolan, J. P., Schladweiler, M. C., Kodavanti, U. P., Evansky, P. A., Costa, D. L., & Watkinson, W. P. (2001). Cardiovascular and thermoregulatory effects of inhaled PM-associated transition metals: A potential interaction between nickel and vanadium sulfate. Toxicological Sciences, 64, 243–252.CrossRefPubMedGoogle Scholar
  28. 28.
    Watkinson, W. P., Campen, M. J., Lyon, J. Y., Highfill, J. W., Wiester, M. J., & Costa, D. L. (1997). Impact of the hypothermic response in inhalation toxicology studies. Annals of the New York Academy of Sciences, 813, 849–863.CrossRefPubMedGoogle Scholar
  29. 29.
    Gordon, C. J., Spencer, P. J., Hotchkiss, J., Miller, D. B., Hinderliter, P. M., & Pauluhn, J. (2008). Thermoregulation and its influence on toxicity assessment. Toxicology, 244, 87–97.CrossRefPubMedGoogle Scholar
  30. 30.
    Sacks, J. D., Stanek, L. W., Luben, T. J., Johns, D. O., Buckley, B. J., Brown, J. S., & Ross, M. (2011). Particulate matter-induced health effects: Who is susceptible? Environmental Health Perspectives, 119, 446–454.CrossRefPubMedGoogle Scholar
  31. 31.
    Bandinelli, S., Corsi, A. M., Milaneschi, Y., & Vazzana, R. (2010). Frailty and the homeostatic network. Acta Bio Medica Atenei Parmensis, 81(Suppl 1), 15–18.PubMedGoogle Scholar
  32. 32.
    Kyriazis, M. (2003). Practical applications of chaos theory to the modulation of human ageing: Nature prefers chaos to regularity. Biogerontology, 4, 75–90.CrossRefPubMedGoogle Scholar
  33. 33.
    Rey-Robert, B., Temprado, J. J., & Berton, E. (2011). Aging and changes in complexity in the neurobehavioral system. Medicina (Kaunas), 47, 1–10.CrossRefGoogle Scholar
  34. 34.
    Lipsitz, L. A. (2004). Physiological complexity, aging, and the path to frailty. Science of Aging Knowledge Environment, 2004, pe16.CrossRefPubMedGoogle Scholar
  35. 35.
    Pikkujamsa, S. M., Makikallio, T. H., Sourander, L. B., Raiha, I. J., Puukka, P., Skytta, J., Peng, C. K., Goldberger, A. L., & Huikuri, H. V. (1999). Cardiac interbeat interval dynamics from childhood to senescence: Comparison of conventional and new measures based on fractals and chaos theory. Circulation, 100, 393–399.CrossRefPubMedGoogle Scholar
  36. 36.
    Xiao, R. P., Tomhave, E. D., Wang, D. J., Ji, X., Boluyt, M. O., Cheng, H., Lakatta, E. G., & Koch, W. J. (1998). Age-associated reductions in cardiac beta1- and beta2-adrenergic responses without changes in inhibitory G proteins or receptor kinases. Journal of Clinical Investigation, 101, 1273–1282.CrossRefPubMedPubMedCentralGoogle Scholar
  37. 37.
    Wang, T., Lang, G. D., Moreno-Vinasco, L., Huang, Y., Goonewardena, S. N., Peng, Y. J., Svensson, E. C., Natarajan, V., Lang, R. M., Linares, J. D., Breysse, P. N., Geyh, A. S., Samet, J. M., Lussier, Y. A., Dudley, S., Prabhakar, N. R., & Garcia, J. G. (2012). Particulate matter induces cardiac arrhythmias via dysregulation of carotid body sensitivity and cardiac sodium channels. American Journal of Respiratory Cell and Molecular Biology, 46(4), 524–531.CrossRefPubMedPubMedCentralGoogle Scholar
  38. 38.
    Wagner, J. G., Allen, K., Yang, H., Nan, B., Morishita, M., Mukherjee, B., Dvonch, J. T., Spino, C., Fink, G. D., Rajagopalan, S., Sun, Q., Brook, R. D., & Harkema, J. R. (2014). Cardiovascular depression in rats exposed to inhaled particulate matter and ozone: Effects of diet-induced metabolic syndrome. Environmental Health Perspectives, 122(1), 27–33.CrossRefPubMedGoogle Scholar
  39. 39.
    Hazari, M. S., Haykal-Coates, N., Winsett, D. W., Costa, D. L., & Farraj, A. K. (2009). A single exposure to particulate or gaseous air pollution increases the risk of aconitine-induced cardiac arrhythmia in hypertensive rats. Toxicological Sciences, 112, 532–542.CrossRefPubMedGoogle Scholar
  40. 40.
    Anselme, F., Loriot, S., Henry, J. P., Dionnet, F., Napoleoni, J. G., Thuillez, C., & Morin, J. P. (2007). Inhalation of diluted diesel engine emission impacts heart rate variability and arrhythmia occurrence in a rat model of chronic ischemic heart failure. Archives of Toxicology, 81(4), 299–307.CrossRefPubMedGoogle Scholar
  41. 41.
    Farraj, A. K., Haykal-Coates, N., Winsett, D. W., Gilmour, M. I., King, C., Krantz, Q. T., Richards, J., & Hazari, M. S. (2015). Comparative electrocardiographic, autonomic and systemic inflammatory responses to soy biodiesel and petroleum diesel emissions in rats. Inhalation Toxicology, 27(11), 564–575.CrossRefPubMedGoogle Scholar
  42. 42.
    Carll, A. P., Crespo, S. M., Filho, M. S., Zati, D. H., Coull, B. A., Diaz, E. A., Raimundo, R. D., Jaeger, T. N. G., Ricci-Vitor, A. L., Papapostolou, V., Lawrence, J. E., Garner, D. M., Perry, B. S., Harkema, J. R., & Godleski, J. J. (2017). Inhaled ambient-level traffic-derived particulates decrease cardiac vagal influence and baroreflexes and increase arrhythmia in a rat model of metabolic syndrome. Particle and Fibre Toxicology, 14, 16.CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Oregon Health & Science University-Portland State University School of Public HealthPortlandUSA
  2. 2.Department of Environmental Health and Engineering, Bloomberg School of Public HealthJohns Hopkins UniversityBaltimoreUSA

Personalised recommendations