Skip to main content
SpringerLink
Log in

Direct and acute cardiotoxicity of ultrafine particles in young adult and old rat hearts

  • ORIGINAL CONTRIBUTION
  • Published:
Basic Research in Cardiology Aims and scope Submit manuscript

Abstract

Background

Air pollution is associated with significant increases in cardiac morbidity and mortality in the general population. The elderly cohort within the general population is considered at high risk for cardiac diseases. However the degree to which air pollutants affect cardiac responses in old hearts vs. their young adult counterparts has not been systematically addressed.

Objectives

We sought to investigate the response of young adult vs. old rat hearts to the direct exposure of ultrafine particles (UFP); i.e. when the UFP are directly instilled into the cardiac vasculature, and their effects are not dependent upon UFP inhalation.

Methods

The study was performed in isolated Langendorff-perfused rat hearts obtained from young adult (4 months old) and aged (26 months old) Fisher 344/Brown Norway rats. Two treatment groups (control and UFP-treated) were studied, and two ages (young adult and old) were studied within each group. Control hearts were perfused with buffer only, UFP-treated hearts were perfused with buffer containing ultrafine particles isolated from industrial diesel reference particulate matter. Systolic and end-diastolic pressures, positive and negative dP/dt, and coronary flow were measured.

Results

Young adult and old hearts demonstrated equal functional deterioration in response to direct infusion of UFP. Developed pressure in young adult UFP-treated hearts fell from 101±4 to 68±8 mmHg (a decrease by 33%, p<0.05). In the old UFP-treated hearts developed pressure fell by 35% (from 101±7 to 67±9mmHg, p<0.05). Positive dP/dt was equally affected in the young adult and old UFP-treated hearts and was decreased by 28% in both groups.

Conclusion

Ultrafine particles when instilled directly into the cardiac vasculature were equally cardiotoxic in young adult and old rat hearts.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

Abbreviations

IDRM:

industrial diesel reference particulate matter

NIST:

National Institute of Standards and Technology

UFP:

ultrafine particles

YC:

young adult control hearts

OC:

old control hearts

YUFP:

young adult hearts treated with ultrafine particles

OUFP:

old hearts treated with ultrafine particles

ROS:

reactive oxygen species

NO:

nitric oxide

References

  1. Anderson HR, Atkinson RW, Bremner SA, Marston L (2003) Particulate air pollution and hospital admissions for cardiorespiratory diseases: are the elderly at greater risk? Eur Resp J 21 (Suppl. 40):39s–46s

    Article  CAS  Google Scholar 

  2. Azhar G, Ahang X, Wang S, Zgong Y, Quick CM, Wei JY (2007) Maintaining serum response factor activity in the older heart equal to that of the young adult is associated with better cardiac response to isoproterenol stress. Basic Res Cardiol 102:233–244

    Article  PubMed  CAS  Google Scholar 

  3. Becker S, Dailey LA, Soukup JM, Grambow SC, Devlin RB, Huang YC (2005) Seasonal variations in air pollution particle-induced inflammatory mediator release and oxidative stress. Environ Health Perspect 113:1032–1038

    PubMed  CAS  Google Scholar 

  4. Besse S, Robert V, Assayag P, Delcayre C, Swynghedauw B (1994) Nonsynchronous changes in myocardial collagen mRNA and protein during aging: effect of DOCA-salt hypertension. Am J Physiol 267:H2237–H2244

    PubMed  CAS  Google Scholar 

  5. Bhatangar A (2006) Environmental cardiology. Studying mechanistic links between pollution and heart disease. Circ Res 99:692–705

    Article  CAS  Google Scholar 

  6. Bolyut MO, Younes A, Caffrey JL, O’Neil L, Barron BA, Crow MT, Lakatta EG (1993) Age-associated increase in rat cardiac opioid production. Am J Physiol 265:H212–H218

    Google Scholar 

  7. Brook RD, Brook JR, Urch B,Vincent R, Rajagopalan S, Silverman F (2002) Inhalation of fine particulate air pollution and ozone causes acute arterial vasoconstriction in healthy adults. Circulation 105:1534–1536

    Article  PubMed  CAS  Google Scholar 

  8. Brook RD, Franklin B, Cascio W, Hong Y, Howard G, Lipsett M, Luepker R, Mittleman M, Samet J, Smith SC, Tager I (2004) Air pollution and cardiovascular disease. A statement for healthcare professionals from the expert panel on population and prevention science of the American Heart Association. Circulation 109:2655–2671

    Article  PubMed  Google Scholar 

  9. Cozzi E, Hazarika S, Stallings HW 3rd, Cascio WE, Devlin RB, Lust RM, Wingard CJ, Van Scott MR (2006) Ultrafine particulate matter exposure augments ischemia-reperfusion injury in mice. Am J Physiol 292:H894–H903

    Google Scholar 

  10. Creason J, Neas L,Walsh D, Williams R, Sheldon L, Liao D, Shy C (2001) Particulate matter and heart rate variability among elderly retirees: the Baltimore 1998 PM study. J Expo Anal Environ Epidemiol 11:116–122

    Article  PubMed  CAS  Google Scholar 

  11. Delfino RJ, Sioutas C, Malik S (2005) Potential role of ultrafine particles in associations between airborn particle mass and cardiovascular health. Environ Health Prospect 113:934–946

    Article  Google Scholar 

  12. Devlin RB, Ghio AJ, Kehrl H, Sanders G, Cascio W (2003) Elderly humans exposed to concentrated air pollution particles have decreased heart rate variability. Eur Respir J 40 (Suppl):76s–80s

    Article  CAS  Google Scholar 

  13. Dominici F, Peng RD, Bell ML, Pham L, McDermott A, Zeger SL, Samet JM (2006) Fine particulate air pollution and hospital admission for cardiovascular and respiratory disease. JAMA 295:1127–1134

    Article  PubMed  CAS  Google Scholar 

  14. Donaldson K, Stone V, Seaton A, MacNee W (2001) Ambient particle inhalation and the cardiovascular system: potential mechanisms. Environ Health Prospect 109:523–527

    Article  CAS  Google Scholar 

  15. Fairley D (1990) The relationship of daily mortality to suspended particulates in Santa Clara County, 1980–1986. Environ Health Prospect 89:159–168

    Article  CAS  Google Scholar 

  16. Furuyama A, Hirano S, Koike E, Kobayashi T (2006) Induction of oxidative stress and inhibition of plasminogen activator inhibitor-1 production in endothelial cells following exposure to organic extracts of diesel exhaust particles and urban fine particles. Arch Toxicol 80:154–162

    Article  PubMed  CAS  Google Scholar 

  17. Gonzalez-Flecha B (2004) Oxidant mechanisms in response to ambient air particles. Mol Aspects Med 25:169–182

    Article  PubMed  CAS  Google Scholar 

  18. Gurgueira SA, Lawrence J, Coull B, Murthy GGK, Gonzalez-Flecha B (2002) Rapid increases in the steady-state concentration of reactive oxygen species in the lungs and heart after particulate air pollution inhalation. Environ Health Perspect 110:749–755

    Article  PubMed  CAS  Google Scholar 

  19. Heymes C, Silvestre JS, Llorens-Cortes C, Chevalier B, Marotte F Levy BI, Swynghedauw B, Samuel JL (1998) Cardiac senescence is associated with enhanced expression of angiotensin II receptor subtypes. Endocrinol 139:2579–2587

    Article  CAS  Google Scholar 

  20. Hoffmann B, Moebus S, Mohlenkamp S, Stang A, Lehmann N, Dragano N, Schmermund A, Memmesheimer M, Mann K, Erbel R, Jockel KH, for the Heinz Nixdorf Recall Study Investigative Group (2007) Residential exposure to traffic is associated with coronary atherosclerosis. Circulation 116:489–496

    Article  PubMed  CAS  Google Scholar 

  21. Holmen BA, Ayala A (2002) Ultrafine PM emissions from natural gas, oxidation-catalyst diesel, and particle-trap diesel heavy-duty transit buses. Environ Sci Technol 36:5041–5050

    Article  PubMed  CAS  Google Scholar 

  22. Honma Y, Tani M, Takayama M, Yamamura K, Hasegawa H (2002) Aging abolishes the cardioprotective effect of combination heat shock and hypoxic preconditioning in reperfused rat hearts. Basic Res Cardiol 97:489–495

    Article  PubMed  CAS  Google Scholar 

  23. Ibald-Mulli A, Stieber J, Wichmann HE, Koenig W, Peters A (2001) Effects of air pollution on blood pressure: a population-based approach. Am J Public Health 91:571–577

    Article  PubMed  CAS  Google Scholar 

  24. Jalaludin B, Morgan G, Lincoln D, Sheppeard V, Simpson R, Corbett S (2006) Associations between ambient air pollution and daily emergency department attendances for cardiovascular disease in the elderly (65 + years), Sydney, Australia. J Exp Sci Environ Epidemiol 16:225–237

    Article  CAS  Google Scholar 

  25. Kajstura J, Cheng W, Sarangarajan R, Li P, Li B, Nitahara JA, Chapnick S, Reiss K, Olivetti G, Anversa P (1996) Necrotic and apoptotic myocyte cell death in the aging heart of Fisher 344 rats. Am J Physiol 271:H1215–H1228

    PubMed  CAS  Google Scholar 

  26. Katsouyanni K, Toulomi G, Samoli E, Gryparis A, Le Tertre A, Monopolis Y, Rossi G, Zmirou D, Ballester F, Boumghar A, Anderson HR,Wojtyniak B, Paldy A, Braunstein R, Pekkanen J, Schindler C, Schwartz J (2001) Confounding and effect modification in the short-term effects of ambient particles on total mortality: results from 29 European cities within the APHEA2 project. Epidemiology 12:521–531

    Article  PubMed  CAS  Google Scholar 

  27. Kim UK, Kim HS, Oh BH, Lee MM, Kim SH, Chae JJ, Choi HS, Choe SC, Lee CC, Park YB (2000) Analysis of mitochondrial DNA deletions in four chambers of failing human heart: hemodynamic stress, age, and disease are important factors. Basic Res Cardiol 95:163–171

    Article  PubMed  CAS  Google Scholar 

  28. Künzli N, Kaiser R, Medina S, Studnicka M, Chanel O, Filliger P, Herry M, Horak F, Puybonnieux-Texier V, Quenel P, Schneider J, Seethaler R,Vergnaud J-C, Sommer H (2002) Public-health impact of outdoor and traffic-related air pollution: a European assessment. Lancet 356:795–801

    Article  Google Scholar 

  29. Lakatta EG (1993) Deficient neuroendocrine regulation of the cardiovascular system with advancing age in healthy humans. Circulation 87:631–636

    PubMed  CAS  Google Scholar 

  30. Lakatta EG (2000) Research agenda for cardiovascular aging: humans to molecules. Am J Geriatr Cardiol 9:251–262

    Article  PubMed  Google Scholar 

  31. Lee JT, Cho YS, Hong YC, Ha EH, Park H (2003) Air pollution and hospital admissions for ischemic heart diseases among individuals 64+ years of age residing in Seoul, Korea. Arch Environ Health 58:617–623

    Article  PubMed  CAS  Google Scholar 

  32. Liao D, Creason J, Shy C, Williams R, Watts R, Zweidinger R (1999) Daily variation of particulate air pollution and poor cardiac autonomic control in the elderly. Environ Health Perspect 107:521–525

    Article  PubMed  CAS  Google Scholar 

  33. MacNee W, Donaldson K (2003) Mechanism of lung injury caused by PM10 and ultrafine particles with special reference to COPD. Eur Resp J 40 (Suppl):47s–51s

    Article  CAS  Google Scholar 

  34. Magari SR, Schwartz J, Williams PL, Hauser R, Smith TJ, Christiani DC (2002) The association between personal measurements of environmental exposure to particulates and heart rate variability. Epidemiology 13:305–310

    Article  PubMed  Google Scholar 

  35. National Air Quality and Emissions Trend Report (2003) www.epa.gov/airtrends/reports.html

  36. Nemmar A, Van Billoen H, Hoylaerts MF, Hoet PHM, Verbruggen A, Nemery B (2001) Passage of intratracheally instilled ultrafine particles from the lung into the systemic circulation in hamster. Am J Respir Crit Care Med 164:1665–1668

    PubMed  CAS  Google Scholar 

  37. Nemmar A, Hoet PH, Vanquickenborne B, Dinsdale D, Thomeer M, Hoylaerts MF, Vanbilloen H, Mortelmans L, Nemery B (2002) Passage of inhaled particles into the blood circulation in humans. Circulation 105:411–414

    Article  PubMed  CAS  Google Scholar 

  38. O’Neil MS, Veves A, Zanobetti A, Sarnat J, Gold DR, Economides PA Horton ES, Schwartz J (2005) Diabetes enhances vulnerability to particulate air pollution-associated impairments in vascular reactivity and endothelial function. Circulation 111:2913–2920

    Article  Google Scholar 

  39. Peters A, Liu E, Verrier RL, Schwartz J, Gold DR, Mittleman M, Baliff J, Oh A, Allen G, Monahan K, Dockery DW (2000) Air pollution and incidence of cardiac arrhythmia. Epidemiology 11:11–17

    Article  PubMed  CAS  Google Scholar 

  40. Pollack JA, Skvorak JP, Nazian SJ, Landon CS, Dietz JR (1997) Alterations in atrial natriuretic peptide (ANP) secretion and renal effects in aging. J Gerontol Series A: Biol Sci Med Sci 52:B196–B202

    CAS  Google Scholar 

  41. Pope CA 3rd, Hansen ML, Long RW, Nielsen KR, Eatough NL, Wilson WE, Eatough DJ (2004) Ambient particulate air pollution, heart rate variability, and blood markers of inflammation of elderly subjects. Environ Health Perspect 112:339–345

    Article  PubMed  Google Scholar 

  42. Rajagopalan S, Sun Q, Chen LC (2005) Particulate pollution and endothelial function. Déjà vu all over again in the air. Circulation 111:2869–2871

    Article  PubMed  Google Scholar 

  43. Schwartz J (1994) What are people dying of on high air pollution days? Environ Health Perspect 64:26–35

    CAS  Google Scholar 

  44. Schwartz J (1999) Air pollution and hospital admissions for heart disease in eight U.S counties. Epidemiology 10:17–22

    PubMed  CAS  Google Scholar 

  45. Simkhovich BZ, Marjoram P, Poizat C, Kedes L, Kloner RA (2003) Age-related changes of cardiac gene expression following myocardial ischemia/reperfusion. Arch Biochem Biophys 420:268–278

    Article  PubMed  CAS  Google Scholar 

  46. Sorensen M, Daneshvar B, Hansen M, Dragsted LO, Hertel O, Knudsen L, Loft S (2003) Personal PM2.5 exposure and markers of oxidative stress in blood. Environ Health Perspect 111:161–166

    Article  PubMed  Google Scholar 

  47. Szibor M, Holtz J (2003) Mitochondria ageing. Basic Res Cardiol 98:210–218

    PubMed  CAS  Google Scholar 

  48. Turcatto S, Turnbull L,Wang GY, Honbo N, Simpson PC, Karliner JS, Baker AJ (2006) Ischemic preconditioning depends on age and gender. Basic Res Cardiol 101:235–243

    Article  CAS  Google Scholar 

  49. Wellenius GA, Schwartz J, Mittleman MA (2006) Particulate air pollution and hospital admissions for congestive heart failure in seven United States cities. Am J Cardiol 97:404–408

    Article  PubMed  CAS  Google Scholar 

  50. Weinberger SE, Drazen JM (1991) Disturbances of respiratory function. In: Wilson JD, Braunwald E, Isselbacher KJ, Martin JB, Fauci AS, Root RK (eds) Harrison’s Principles of Internal Medicine. Twelfth Edition, McGraw-Hill, Inc. New York, pp 1037 ff

  51. White HD, Barbash GI, Califf RM, Simes RJ, Granger CB, Weaver WD, Kleiman NS, Aylward PE, Gore JM, Vahanian A, Lee KL, Ross AM, Topol EJ (1996) Age and outcome with contemporary thrombolytic therapy. Results from the GUSTO-I trial. Circulation 94:1826–1833

    PubMed  CAS  Google Scholar 

  52. Wichmann HE, Mueller W, Allhoff P, Bechmann M, Bocter N, Csicsaky MJ, Jung MJ, Molik M, Schoeneberg G (1989) Health effects during a smog episode in West Germany in 1985. Environ Health Perspect 79:89–99

    Article  PubMed  CAS  Google Scholar 

  53. Wold LE, Simkhovich BZ, Kleinman MT, Nordlie MA, Dow JS, Sioutas C, Kloner RA (2006) In vivo and in vitro models to test the hypothesis of particle-induced effects on cardiac function and arrhythmias. Cardiovasc Toxicol 6:69–78

    Article  PubMed  CAS  Google Scholar 

  54. Xia T, Kovochich M, Brant J, Hotze M, Sempf J, Oberley T, Sioutas K, Yeh JI, Wiesner MR, Nel AE (2006) Comparison of the abilities of ambient and manufactured nanoparticles to induce cellular toxicity according to an oxidative stress paradigm. Nano Lett 6:1794–1807

    Article  PubMed  CAS  Google Scholar 

  55. Zanobetti A, J Canner MJ, Stone PH, Schwartz J, Sher D, Eagan-Bengston E, Gates KA, Hartley LH, Suh H, Gold DR (2004) Ambient air pollution and blood pressure in cardiac rehabilitation patients. Circulation 110:2184–2189

    Article  PubMed  Google Scholar 

  56. Zhu Y, Kim WC, Sioutas C (2002) Concentration and size distribution of ultrafine particles near a major highway. J Air Waste Manag Assoc 52:1032–1042

    PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. The Heart Institute, Good Samaritan Hospital, 1225 Wilshire Boulevard, Los Angeles (CA), 90017, USA

    Boris Z. Simkhovich & Robert A. Kloner

  2. Division of Cardiovascular Medicine, Keck School of Medicine, University of Southern California, Los Angeles (CA), USA

    Boris Z. Simkhovich & Robert A. Kloner

  3. Dept. of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles (CA), USA

    Paul Marjoram

  4. Dept. of Community and Environmental Medicine, University of California Irvine, Irvine (CA), USA

    Michael T. Kleinman

Authors
  1. Boris Z. Simkhovich
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Paul Marjoram
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Michael T. Kleinman
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Robert A. Kloner
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Boris Z. Simkhovich.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Simkhovich, B.Z., Marjoram, P., Kleinman, M.T. et al. Direct and acute cardiotoxicity of ultrafine particles in young adult and old rat hearts. Basic Res Cardiol 102, 467–475 (2007). https://doi.org/10.1007/s00395-007-0681-0

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00395-007-0681-0

Key words

Search

Navigation