Cardiovascular Toxicology

, Volume 17, Issue 2, pp 97–108 | Cite as

Acrolein Inhalation Alters Myocardial Synchrony and Performance at and Below Exposure Concentrations that Cause Ventilatory Responses

  • Leslie C. Thompson
  • Allen D. Ledbetter
  • Najwa Haykal-Coates
  • Wayne E. Cascio
  • Mehdi S. Hazari
  • Aimen K. Farraj
Article

Abstract

Acrolein is an irritating aldehyde generated during combustion of organic compounds. Altered autonomic activity has been documented following acrolein inhalation, possibly impacting myocardial synchrony and function. Given the ubiquitous nature of acrolein in the environment, we sought to better define the immediate and delayed functional cardiac effects of acrolein inhalation in vivo. We hypothesized that acrolein inhalation would increase markers of cardiac mechanical dysfunction, i.e., myocardial dyssynchrony and performance index in mice. Male C57Bl/6J mice were exposed to filtered air (FA) or acrolein (0.3 or 3.0 ppm) for 3 h in whole-body plethysmography chambers (n = 6). Echocardiographic analyses were performed 1 day before exposure and at 1 and 24 h post-exposure. Speckle tracking echocardiography revealed that circumferential strain delay (i.e., dyssynchrony) was increased at 1 and 24 h following exposure to 3.0 ppm, but not 0.3 ppm, when compared to pre-exposure and/or FA exposure. Pulsed wave Doppler of transmitral blood flow revealed that acrolein exposure at 0.3 ppm, but not 3.0 ppm, increased the Tei index of myocardial performance (i.e., decreased global heart performance) at 1 and 24 h post-exposure compared to pre-exposure and/or FA exposure. We conclude that short-term inhalation of acrolein can acutely modify cardiac function in vivo and that echocardiographic evaluation of myocardial synchrony and performance following exposure to other inhaled pollutants could provide broader insight into the health effects of air pollution.

Keywords

Acrolein Echocardiography Myocardial strain Myocardial dyssynchrony Tei index 

Notes

Acknowledgments

We would like to acknowledge John Havel for his outstanding effort generating the illustrations in Figs. 1 and 2. Judy Richards at USEPA conducted the Konelab assays on the BAL fluid samples. Finally, we would like to thank Dr. Ian Gilmour, Dr. Jan Dye, and Dr. Chris Gordon of the USEPA for their thorough review of this manuscript before submission.

Supplementary material

12012_2016_9360_MOESM1_ESM.docx (742 kb)
Supplementary material 1 (DOCX 741 kb)

References

  1. 1.
    Brook, R. D., Rajagopalan, S., Pope, C. A, 3rd, Brook, J. R., Bhatnagar, A., Diez-Roux, A. V., et al. (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
  2. 2.
    Moghe, A., Ghare, S., Lamoreau, B., Mohammad, M., Barve, S., McClain, C., & Joshi-Barve, S. (2015). Molecular mechanisms of acrolein toxicity: Relevance to human disease. Toxicological Sciences, 143, 242–255.CrossRefPubMedPubMedCentralGoogle Scholar
  3. 3.
    EPA. (2003). Toxicological review of acrolein (CAS No. 107-02-8). Washington, DC: US Environmental Protection Agency.Google Scholar
  4. 4.
    ATSDR. (2007). Toxicological profile for acrolein. U.S: Department of Health and Human Services, Public Health Service, Atlanta, GA.Google Scholar
  5. 5.
    Haussmann, H. J. (2012). Use of hazard indices for a theoretical evaluation of cigarette smoke composition. Chemical Research in Toxicology, 25, 794–810.CrossRefPubMedGoogle Scholar
  6. 6.
    DeJarnett, N., Conklin, D. J., Riggs, D. W., Myers, J. A., O’Toole, T. E., Hamzeh, I., et al. (2014). Acrolein exposure is associated with increased cardiovascular disease risk. Journal of the American Heart Association, 3, e000934. doi: 10.1161/JAHA.114.000934.CrossRefPubMedPubMedCentralGoogle Scholar
  7. 7.
    Perez, C. M., Ledbetter, A. D., Hazari, M. S., Haykal-Coates, N., Carll, A. P., Winsett, D. W., et al. (2013). Hypoxia stress test reveals exaggerated cardiovascular effects in hypertensive rats after exposure to the air pollutant acrolein. Toxicological Sciences, 132, 467–477.CrossRefPubMedPubMedCentralGoogle Scholar
  8. 8.
    Hazari, M. S., Griggs, J., Winsett, D. W., Haykal-Coates, N., Ledbetter, A., Costa, D. L., & Farraj, A. K. (2014). A single exposure to acrolein desensitizes baroreflex responsiveness and increases cardiac arrhythmias in normotensive and hypertensive rats. Cardiovascular Toxicology, 14, 52–63.CrossRefPubMedGoogle Scholar
  9. 9.
    Luo, J., Hill, B. G., Gu, Y., Cai, J., Srivastava, S., Bhatnagar, A., & Prabhu, S. D. (2007). Mechanisms of acrolein-induced myocardial dysfunction: Implications for environmental and endogenous aldehyde exposure. American Journal of Physiology Heart and Circulatory Physiology, 293, H3673–H3684.CrossRefPubMedGoogle Scholar
  10. 10.
    Wang, L., Sun, Y., Asahi, M., & Otsu, K. (2011). Acrolein, an environmental toxin, induces cardiomyocyte apoptosis via elevated intracellular calcium and free radicals. Cell Biochemistry and Biophysics, 61, 131–136.CrossRefPubMedGoogle Scholar
  11. 11.
    Wu, Z., He, E. Y., Scott, G. I., & Ren, J. (2015). Alpha, beta-unsaturated aldehyde pollutant acrolein suppresses cardiomyocyte contractile function: Role of TRPV1 and oxidative stress. Environmental Toxicology, 30, 638–647.CrossRefPubMedGoogle Scholar
  12. 12.
    Stypmann, J., Engelen, M. A., Troatz, C., Rothenburger, M., Eckardt, L., & Tiemann, K. (2009). Echocardiographic assessment of global left ventricular function in mice. Laboratory Animals, 43, 127–137.CrossRefPubMedGoogle Scholar
  13. 13.
    Dandel, M., Lehmkuhl, H., Knosalla, C., Suramelashvili, N., & Hetzer, R. (2009). Strain and strain rate imaging by echocardiography—Basic concepts and clinical applicability. Current Cardiology Reviews, 5, 133–148.CrossRefPubMedPubMedCentralGoogle Scholar
  14. 14.
    Thavendiranathan, P., Poulin, F., Lim, K. D., Plana, J. C., Woo, A., & Marwick, T. H. (2014). Use of myocardial strain imaging by echocardiography for the early detection of cardiotoxicity in patients during and after cancer chemotherapy: A systematic review. Journal of the American College of Cardiology, 63, 2751–2768.CrossRefPubMedGoogle Scholar
  15. 15.
    Tei, C., Ling, L. H., Hodge, D. O., Bailey, K. R., Oh, J. K., Rodeheffer, R. J., et al. (1995). New index of combined systolic and diastolic myocardial performance: A simple and reproducible measure of cardiac function—a study in normals and dilated cardiomyopathy. Journal of Cardiology, 26, 357–366.PubMedGoogle Scholar
  16. 16.
    Caro, A. C., Hankenson, F. C., & Marx, J. O. (2013). Comparison of thermoregulatory devices used during anesthesia of C57BL/6 mice and correlations between body temperature and physiologic parameters. Journal of the American Association for Laboratory Animal Science, 52, 577–583.PubMedPubMedCentralGoogle Scholar
  17. 17.
    Jaskot, R. H., Charlet, E. G., Grose, E. C., Grady, M. A., & Roycroft, J. H. (1983). An automated analysis of glutathione peroxidase, S-transferase, and reductase activity in animal tissue. Journal of Analytical Toxicology, 7, 86–88.CrossRefPubMedGoogle Scholar
  18. 18.
    Perez, C. M., Hazari, M. S., Ledbetter, A. D., Haykal-Coates, N., Carll, A. P., Cascio, W. E., et al. (2015). Acrolein inhalation alters arterial blood gases and triggers carotid body-mediated cardiovascular responses in hypertensive rats. Inhalation Toxicology, 27, 54–63.CrossRefPubMedPubMedCentralGoogle Scholar
  19. 19.
    Shen, M. J., & Zipes, D. P. (2014). Role of the autonomic nervous system in modulating cardiac arrhythmias. Circulation Research, 114, 1004–1021.CrossRefPubMedGoogle Scholar
  20. 20.
    Paton, J. F., Boscan, P., Pickering, A. E., & Nalivaiko, E. (2005). The yin and yang of cardiac autonomic control: Vago-sympathetic interactions revisited. Brain Research. Brain Research Reviews, 49, 555–565.CrossRefPubMedGoogle Scholar
  21. 21.
    Gimelli, A., Liga, R., Genovesi, D., Giorgetti, A., Kusch, A., & Marzullo, P. (2014). Association between left ventricular regional sympathetic denervation and mechanical dyssynchrony in phase analysis: A cardiac CZT study. European Journal of Nuclear Medicine and Molecular Imaging, 41, 946–955.CrossRefPubMedGoogle Scholar
  22. 22.
    Schlack, W., Schafer, S., & Thamer, V. (1994). Left stellate ganglion block impairs left ventricular function. Anesthesia and Analgesia, 79, 1082–1088.CrossRefPubMedGoogle Scholar
  23. 23.
    Schlack, W., & Thamer, V. (1996). Unilateral changes of sympathetic tone to the heart impair left ventricular function. Acta Anaesthesiologica Scandinavica, 40, 262–271.CrossRefPubMedGoogle Scholar
  24. 24.
    Sequeira, I. M., Haberberger, R. V., & Kummer, W. (2005). Atrial and ventricular rat coronary arteries are differently supplied by noradrenergic, cholinergic and nitrergic, but not sensory nerve fibres. Annals of Anatomy, 187, 345–355.CrossRefPubMedGoogle Scholar
  25. 25.
    Reant, P., Labrousse, L., Lafitte, S., Bordachar, P., Pillois, X., Tariosse, L., et al. (2008). Experimental validation of circumferential, longitudinal, and radial 2-dimensional strain during dobutamine stress echocardiography in ischemic conditions. Journal of the American College of Cardiology, 51, 149–157.CrossRefPubMedGoogle Scholar
  26. 26.
    Winter, R., Jussila, R., Nowak, J., & Brodin, L. A. (2007). Speckle tracking echocardiography is a sensitive tool for the detection of myocardial ischemia: A pilot study from the catheterization laboratory during percutaneous coronary intervention. Journal of the American Society of Echocardiography, 20, 974–981.CrossRefPubMedGoogle Scholar
  27. 27.
    Marwick, T. H. (2006). Measurement of strain and strain rate by echocardiography: Ready for prime time? Journal of the American College of Cardiology, 47, 1313–1327.CrossRefPubMedGoogle Scholar
  28. 28.
    Lee, A. P., Zhang, Q., Yip, G., Fang, F., Liang, Y. J., Xie, J. M., et al. (2011). LV mechanical dyssynchrony in heart failure with preserved ejection fraction complicating acute coronary syndrome. JACC Cardiovascular Imaging, 4, 348–357.CrossRefPubMedGoogle Scholar
  29. 29.
    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, 69–78.CrossRefPubMedPubMedCentralGoogle Scholar
  30. 30.
    Ghilarducci, D. P., & Tjeerdema, R. S. (1995). Fate and effects of acrolein. Reviews of Environmental Contamination and Toxicology, 144, 95–146.PubMedGoogle Scholar
  31. 31.
    Moretto, N., Volpi, G., Pastore, F., & Facchinetti, F. (2012). Acrolein effects in pulmonary cells: Relevance to chronic obstructive pulmonary disease. Annals of the New York Academy of Sciences, 1259, 39–46.CrossRefPubMedGoogle Scholar
  32. 32.
    Pagel, P. S., Nijhawan, N., & Warltier, D. C. (1993). Quantitation of volatile anesthetic-induced depression of myocardial contractility using a single beat index derived from maximal ventricular power. Journal of Cardiothoracic and Vascular Anesthesia, 7, 688–695.CrossRefPubMedGoogle Scholar
  33. 33.
    Hatakeyama, N., Ito, Y., & Momose, Y. (1993). Effects of sevoflurane, isoflurane, and halothane on mechanical and electrophysiologic properties of canine myocardium. Anesthesia and Analgesia, 76, 1327–1332.CrossRefPubMedGoogle Scholar
  34. 34.
    Palmisano, B. W., Mehner, R. W., Stowe, D. F., Bosnjak, Z. J., & Kampine, J. P. (1994). Direct myocardial effects of halothane and isoflurane. Comparison between adult and infant rabbits. Anesthesiology, 81, 718–729.CrossRefPubMedGoogle Scholar
  35. 35.
    Lairez, O., Lonjaret, L., Ruiz, S., Marchal, P., Franchitto, N., Calise, D., et al. (2013). Anesthetic regimen for cardiac function evaluation by echocardiography in mice: Comparison between ketamine, etomidate and isoflurane versus conscious state. Laboratory Animals, 47, 284–290.CrossRefPubMedGoogle Scholar
  36. 36.
    Lynch, P. J., & Jaffe, C. C. (2006). Heart normal short axis section. New Haven, CT: Creative Commons.Google Scholar
  37. 37.
    Lynch, P. J., & Jaffe, C. C. (2006). Heart apical 4c anatomy. New Haven, CT: Creative Commons.Google Scholar

Copyright information

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

Authors and Affiliations

  • Leslie C. Thompson
    • 1
  • Allen D. Ledbetter
    • 1
  • Najwa Haykal-Coates
    • 1
  • Wayne E. Cascio
    • 1
  • Mehdi S. Hazari
    • 1
  • Aimen K. Farraj
    • 1
  1. 1.Environmental Public Health DivisionUnited States Environmental Protection Agency (USEPA)Research Triangle ParkUSA

Personalised recommendations