Basic Research in Cardiology

, Volume 102, Issue 6, pp 467–475 | Cite as

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

  • Boris Z. Simkhovich
  • Paul Marjoram
  • Michael T. Kleinman
  • Robert A. Kloner



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.


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.


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.


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.


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

Key words

air pollution ultrafine particles cardiotoxicity 



industrial diesel reference particulate matter


National Institute of Standards and Technology


ultrafine particles


young adult control hearts


old control hearts


young adult hearts treated with ultrafine particles


old hearts treated with ultrafine particles


reactive oxygen species


nitric oxide


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 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–46sCrossRefGoogle Scholar
  2. 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 102:233–244CrossRefPubMedGoogle Scholar
  3. 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 113:1032–1038PubMedGoogle Scholar
  4. 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–H2244PubMedGoogle Scholar
  5. 5.
    Bhatangar A (2006) Environmental cardiology. Studying mechanistic links between pollution and heart disease. Circ Res 99:692–705CrossRefGoogle Scholar
  6. 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–H218Google Scholar
  7. 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 105:1534–1536CrossRefPubMedGoogle Scholar
  8. 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 109:2655–2671CrossRefPubMedGoogle Scholar
  9. 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–H903Google Scholar
  10. 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 11:116–122CrossRefPubMedGoogle Scholar
  11. 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 113:934–946CrossRefGoogle Scholar
  12. 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–80sCrossRefGoogle Scholar
  13. 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 295:1127–1134CrossRefPubMedGoogle Scholar
  14. 14.
    Donaldson K, Stone V, Seaton A, MacNee W (2001) Ambient particle inhalation and the cardiovascular system: potential mechanisms. Environ Health Prospect 109:523–527CrossRefGoogle Scholar
  15. 15.
    Fairley D (1990) The relationship of daily mortality to suspended particulates in Santa Clara County, 1980–1986. Environ Health Prospect 89:159–168CrossRefGoogle Scholar
  16. 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 80:154–162CrossRefPubMedGoogle Scholar
  17. 17.
    Gonzalez-Flecha B (2004) Oxidant mechanisms in response to ambient air particles. Mol Aspects Med 25:169–182CrossRefPubMedGoogle Scholar
  18. 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 110:749–755PubMedCrossRefGoogle Scholar
  19. 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 139:2579–2587CrossRefGoogle Scholar
  20. 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 116:489–496CrossRefPubMedGoogle Scholar
  21. 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 36:5041–5050CrossRefPubMedGoogle Scholar
  22. 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 97:489–495CrossRefPubMedGoogle Scholar
  23. 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 91:571–577CrossRefPubMedGoogle Scholar
  24. 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 16:225–237CrossRefGoogle Scholar
  25. 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–H1228PubMedGoogle Scholar
  26. 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 12:521–531CrossRefPubMedGoogle Scholar
  27. 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 95:163–171CrossRefPubMedGoogle Scholar
  28. 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 356:795–801CrossRefGoogle Scholar
  29. 29.
    Lakatta EG (1993) Deficient neuroendocrine regulation of the cardiovascular system with advancing age in healthy humans. Circulation 87:631–636PubMedGoogle Scholar
  30. 30.
    Lakatta EG (2000) Research agenda for cardiovascular aging: humans to molecules. Am J Geriatr Cardiol 9:251–262CrossRefPubMedGoogle Scholar
  31. 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 58:617–623CrossRefPubMedGoogle Scholar
  32. 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 107:521–525CrossRefPubMedGoogle Scholar
  33. 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–51sCrossRefGoogle Scholar
  34. 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 13:305–310CrossRefPubMedGoogle Scholar
  35. 35.
    National Air Quality and Emissions Trend Report (2003) Scholar
  36. 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 164:1665–1668PubMedGoogle Scholar
  37. 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 105:411–414CrossRefPubMedGoogle Scholar
  38. 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 111:2913–2920CrossRefGoogle Scholar
  39. 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 11:11–17CrossRefPubMedGoogle Scholar
  40. 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–B202Google Scholar
  41. 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 112:339–345PubMedCrossRefGoogle Scholar
  42. 42.
    Rajagopalan S, Sun Q, Chen LC (2005) Particulate pollution and endothelial function. Déjà vu all over again in the air. Circulation 111:2869–2871CrossRefPubMedGoogle Scholar
  43. 43.
    Schwartz J (1994) What are people dying of on high air pollution days? Environ Health Perspect 64:26–35Google Scholar
  44. 44.
    Schwartz J (1999) Air pollution and hospital admissions for heart disease in eight U.S counties. Epidemiology 10:17–22PubMedGoogle Scholar
  45. 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 420:268–278CrossRefPubMedGoogle Scholar
  46. 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 111:161–166PubMedCrossRefGoogle Scholar
  47. 47.
    Szibor M, Holtz J (2003) Mitochondria ageing. Basic Res Cardiol 98:210–218PubMedGoogle Scholar
  48. 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 101:235–243CrossRefGoogle Scholar
  49. 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 97:404–408CrossRefPubMedGoogle Scholar
  50. 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 ffGoogle Scholar
  51. 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 94:1826–1833PubMedGoogle Scholar
  52. 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 79:89–99CrossRefPubMedGoogle Scholar
  53. 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 6:69–78CrossRefPubMedGoogle Scholar
  54. 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 6:1794–1807CrossRefPubMedGoogle Scholar
  55. 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 110:2184–2189CrossRefPubMedGoogle Scholar
  56. 56.
    Zhu Y, Kim WC, Sioutas C (2002) Concentration and size distribution of ultrafine particles near a major highway. J Air Waste Manag Assoc 52:1032–1042PubMedGoogle Scholar

Copyright information

© Steinkopff-Verlag 2007

Authors and Affiliations

  • Boris Z. Simkhovich
    • 1
    • 2
  • Paul Marjoram
    • 3
  • Michael T. Kleinman
    • 4
  • Robert A. Kloner
    • 1
    • 2
  1. 1.The Heart InstituteGood Samaritan HospitalLos Angeles (CA)USA
  2. 2.Division of Cardiovascular Medicine, Keck School of MedicineUniversity of Southern CaliforniaLos Angeles (CA)USA
  3. 3.Dept. of Preventive Medicine, Keck School of MedicineUniversity of Southern CaliforniaLos Angeles (CA)USA
  4. 4.Dept. of Community and Environmental MedicineUniversity of California IrvineIrvine (CA)USA

Personalised recommendations