|University of Rochester|
School of Medicine & Dentistry
|Molecular Toxicology & Environmental Medicine Cluster|
|Ph.D. Program in Toxicology|
Mark W. Frampton|
Professor of Medicine and Environmental Medicine
M.D. 1973 (New York University)
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.
Stewart JC, Chalupa DC, Devlin RB, Frasier LM, Huang LS, Little EL, Lee SM, Phipps RP, Pietropaoli AP, Taubman MB, Utell MJ, and Frampton MW. Vascular effects of ultrafine particles in persons with type 2 diabetes. Environ Health Perspect. 2010 Dec;118(12):1692-1698.
Hampel R, Breitner S, Rückerl R, Frampton MW, Koenig W, Phipps RP, Wichmann HE, Peters A, and Schneider A. Air temperature and inflammatory and coagulation responses in men with coronary or pulmonary disease during the winter season. Occup Environ Med. 2010 Jun;67(6):408-416.
Fanning EW, Froines JR, Utell MJ, Lippmann M, Oberdörster G, Frampton M, Godleski J, and Larson TV. Particulate matter (PM) research centers (1999-2005) and the role of interdisciplinary center-based research. Environ Health Perspect. 2009 Feb;117(2):167-174.
Shah AP, Pietropaoli AP, Frasier LM, Speers DM, Chalupa DC, Delehanty JM, Huang LS, Utell MJ, and Frampton MW. Effect of inhaled carbon ultrafine particles on reactive hyperemia in healthy human subjects. Environ Health Perspect. 2008 Mar;116(3):375-380.
Frampton MW, Stewart JC, Oberdorster G, Morrow PE, Chalupa D, Pietropaoli AP, Frasier LM, Speers DM, Cox C, Huang LS, and 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, andPeters 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
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
Faculty Listed by Research Areas
Toxicology Cluster Home Page
Department of Environmental Medicine
University of Rochester Medical Center
January 21 2011 (vgl)