Cardiovascular Effects of Ultrafine Particles

Each day the average person breathes about 15,000 liters, or approximately 35 pounds, of air. Gaseous and particulate contaminants in that air gain access to the body with each breath, and may have both short and long-term effects on human health. Our ongoing studies examine the effects of particle exposure on lung function, airway inflammation, and cardiovascular function.

Utilizing both environmental chamber and mouthpiece exposure systems, subjects are exposed to environmentally relevant concentrations of pollutants, with or without exercise. Respiratory and systemic effects are determined using measures of lung function, recovery inflammatory cells from the airways using sputum induction, examination for markers of inflammation in exhaled air, characterization of blood leukocyte responses using 3-color flow cytometry, and detailed cardiovascular monitoring.

Ultrafine particles (UFP, <100 nm diameter) may be particularly important with regard to cardiovascular effects because of their potential for evading clearance mechanisms and entering the lung interstitium and vascular space. We have demonstrated in healthy nonsmokers that inhalation of low concentrations of UFP causes changes in blood oxygen saturation and leukocyte expression of adhesion molecules that are consistent with altered endothelial function.

Smokers and the elderly may be more susceptible to vascular effects of particle exposure because of impaired endothelial function and increased risk for atherosclerosis. Our studies explore the hypothesis that inhalation of ultrafine particles alters endothelial function in healthy and susceptible people. Endothelial dysfunction is critically linked to the pathogenesis of atherosclerotic vascular disease.

Exposure to air pollution particles appears to increase the risk of arrhythmias in patients with heart disease. Factors affecting myocardial repolarization can influence the susceptibility to arrhythmias. We found that UFP inhalation induced alterations in the cardiac QT interval, which could not be entirely explained by changes in heart rate or heart rate variability (HRV). This suggests an effect on ventricular myocardium mediated by the autonomic nervous system, and/or a direct effect of UFP on myocardial ion channels that govern repolarization. Our studies also test the hypothesis that inhalation of UFP alters ventricular repolarization. Data from these human clinical studies of exposure to air pollutants help to elucidate the mechanisms responsible for pollutant health effects, and assist in establishing rational air quality standards.

Recent Publications

Frampton MW, Stewart JC, Oberdorster G, Morrow PE, Chalupa D, Pietropaoli AP, Frasier LM, Speers DM, Cox C, Huang LS, Utell MJ. 2006. Inhalation of ultrafine particles alters blood leukocyte expression of adhesion molecules in humans. Environ Health Perspect. Jan;114(1):51-58.

Ruckerl R, Ibald-Mulli A, Koenig W, Schneider A, Woelke G, Cyrys J, Heinrich J, Marder V, Frampton M, Wichmann HE, Peters A. 2006. Air pollution and markers of inflammation and coagulation in patients with coronary heart disease. Am J Respir Crit Care Med. Feb 15;173(4):432-441

Frampton MJ, Akdas H, Cowley AR, Rogers JE, Slagle JE, Fleitz PA, Drobizhev M, Rebane A, Anderson HL. 2005. Synthesis, crystal structure, and nonlinear optical behavior of beta-unsubstituted meso-meso E-vinylene-linked porphyrin dimers. Org Lett. Nov 24;7(24):5365-8.

Devlin RB, Frampton ML, Ghio AJ. 2005. In vitro studies: what is their role in toxicology? Exp Toxicol Pathol. Jul;57 Suppl 1:183-188.

Frampton MW, Utell MJ, Zareba W, Oberdorster G, Cox C, Huang LS, Morrow PE, Lee FE, Chalupa D, Frasier LM, Speers DM, Stewart J. 2004. Effects of exposure to ultrafine carbon particles in healthy subjects and subjects with asthma. Res Rep Health Eff Inst. Dec;(126):1-47; discussion 49-63.

Beckett WS, Chalupa DF, Pauly-Brown A, Speers DM, Stewart JC, Frampton MW, Utell MJ, Huang LS, Cox C, Zareba W, Oberdorster G. 2005. Comparing inhaled ultrafine versus fine zinc oxide particles in healthy adults: a human inhalation study. Am J Respir Crit Care Med. May 15;171(10):1129-1135

Pietropaoli AP, Frampton MW, Hyde RW, Morrow PE, Oberdorster G, Cox C, Speers DM, Frasier LM, Chalupa DC, Huang LS, and Utell MJ. 2004. Pulmonary function, diffusing capacity, and inflammation in healthy and asthmatic subjects exposed to ultrafine particles. Inhal Toxicol. 16 Suppl 1:59-72.

Elder ACP, Gelein R, Finkelstein J, Phipps R, Frampton M, Utell M, Topham D, Kittelson D, Watts W, Hopke P, Jeong C-H, Kim E, Liu W, Zhao W, Zhou L, Vincent R, Kumarathasan P, and Oberdörster G. On-road exposure to highway aerosols. 2. Exposures of aged, compromised rats. Inhalation Toxicol, 16 Suppl 1:41-53. .

Elder AC, Gelein R, Azadniv M, Frampton M, Finkelstein J, Oberdorster G. Systemic effects of inhaled ultrafine particles in two compromised, aged rat strains. Inhal Toxicol. Jun;16(6-7):461-471.

Chalupa DC, Morrow PE, Oberdorster G, Utell MJ, and Frampton MW. 2004. Ultrafine particle deposition in subjects with asthma. Environ Health Perspect. Jun;112(8):879-882.

Lippmann M, Frampton M, Schwartz J, Dockery D, Schlesinger R, Koutrakis P, Froines J, Nel A, Finkelstein J, Godleski J, Kaufman J, Koenig J, Larson T, Luchtel D, Liu LJ, Oberdörster G, Peters A, Sarnat J, Sioutas C, Suh H, Sullivan J, Utell M, Wichmann E, Zelikoff J. 2003. The U.S. Environmental Protection Agency Particulate Matter Health Effects Research Centers Program: a midcourse report of status, progress, and plans. Environ Health Perspect. Jun;111(8):1074-1092.

Hjort MR, Brenyo AJ, Finkelstein JN, Frampton MW, LoMonaco MB, Stewart JC, Johnston CJ, and D'Angio CT. 2003. Alveolar epithelial cell-macrophage interactions affect oxygen-stimulated interleukin-8 release. Inflammation. Jun;27(3):137-145.

Daigle CC, Chalupa DC, Gibb FR, Morrow PE, Oberdörster G, Utell MJ, and Frampton MW. 2003. Ultrafine particle deposition in humans during rest and exercise. Inhal Toxicol. Jun;15(6):539-552.