RESEARCH REPORT Effect of Concentrated Ambient Particulate Matter on Blood Coagulation Parameters in Rats

CoverSpread.qxd 10/30/2002 12:31 PM Page 1 RESEARCH REPORT Effect of Concentrated Ambient Particulate Matter on Blood Charlestown Navy Yard Number 111 Coagulation Parameters in Rats 120 Second Avenue October 2002 Christine Nadziejko, Kaijie Fang, Lung Chi Chen, Beverly Cohen, Boston MA 02129-4533 USA Margaret Karpatkin, and Arthur Nadas +1-617-886-9330 www.healtheffects.org RESEARCH REPORT Number 111 October 2002 CoverSpread.qxd 10/25/2002 12:41 PM Page 2 BOARD OF DIRECTORS Richard F Celeste Chair Purnell W Choppin President, Colorado College President Emeritus, Howard Hughes Medical Institute Donald Kennedy Vice Chair Alice Huang The Health Effects Institute, established Editor-in-Chief, Science; President (Emeritus) and Bing Professor of Senior Councilor for External Relations, California Institute HEALTH Biological Sciences, Stanford University of Technology EFFECTS in 1980, is an independent and unbiased Richard B Stewart INSTITUTE source of information on the health Archibald Cox Chair Emeritus University Professor, New York University School of Law, and Director, Carl M Loeb University Professor (Emeritus), Harvard Law School New York University Center on Environmental and Land Use Law effects of motor vehicle emissions. HEI Robert M White studies all major pollutants, including President (Emeritus), National Academy of Engineering, and Senior Fellow, University Corporation for Atmospheric Research regulated pollutants (such as carbon monoxide, ozone, nitrogen dioxide, and HEALTH RESEARCH COMMITTEE particulate matter) and unregulated Mark J Utell Chair Stephen I Rennard Professor of Medicine and Environmental Medicine, University Larson Professor, Department of Internal Medicine, University of pollutants (such as diesel engine exhaust, of Rochester Nebraska Medical Center methanol, and aldehydes). To date, HEI Melvyn C Branch Howard Rockette Professor and Associate Dean, College of Engineering and Applied Professor and Chair, Department of Biostatistics, Graduate School of has supported more than 200 projects at Science, University of Colorado Public Health, University of Pittsburgh institutions in North America and Europe Kenneth L Demerjian Jonathan M Samet Professor and Director, Atmospheric Sciences Research Center, Professor and Chairman, Department of Epidemiology, Bloomberg and has published over 130 research University at Albany, State University of New York School of Public Health, Johns Hopkins University reports. Peter B Farmer Frank E Speizer Professor and Section Head, Medical Research Council Toxicology Unit, Edward H Kass Professor of Medicine, Channing Laboratory, Harvard Typically, HEI receives half its funds University of Leicester Medical School and Department of Medicine, Brigham and Women’s from the US Environmental Protection Helmut Greim Hospital Agency and half from 28 manufacturers Professor, Institute of Toxicology and Environmental Hygiene, Technical Clarice R Weinberg University of Munich Chief, Biostatistics Branch, Environmental Diseases and Medicine and marketers of motor vehicles and Rogene Henderson Program, National Institute of Environmental Health Sciences engines in the United States. Senior Scientist and Deputy Director, National Environmental Respiratory Center, Lovelace Respiratory Research Institute Occasionally, funds from other public and private organizations either support HEALTH REVIEW COMMITTEE Daniel C Tosteson Chair Thomas A Louis special projects or provide resources for Professor of Cell Biology, Dean Emeritus, Harvard Medical School Professor, Department of Biostatistics, Bloomberg School of Public a portion of an HEI study. Regardless of Ross Anderson Health, Johns Hopkins University funding sources, HEI exercises complete Professor and Head, Department of Public Health Sciences, Edo D Pellizzari St George’s Hospital Medical School, London University Vice President for Analytical and Chemical Sciences, Research autonomy in setting its research John C Bailar III Triangle Institute priorities and in reaching its Professor Emeritus, The University of Chicago Nancy Reid John R Hoidal Professor and Chair, Department of Statistics, University of Toronto conclusions. An independent Board of Professor of Medicine and Chief of Pulmonary/Critical Medicine, William N Rom Directors governs HEI. The Institute’s University of Utah Professor of Medicine and Environmental Medicine and Chief of Pulmonary and Critical Care Medicine, New York University Health Research and Health Review Thomas W Kensler Professor, Division of Toxicological Sciences, Department of Medical Center Committees serve complementary Environmental Sciences, Johns Hopkins University Sverre Vedal Professor, University of Colorado School of Medicine; Senior Faculty, scientific purposes and draw Brian Leaderer Professor, Department of Epidemiology and Public Health, Yale National Jewish Medical and Research Center distinguished scientists as members. University School of Medicine The results of HEI-funded studies are OFFICERS & STAFF made available as Research Reports, Daniel S Greenbaum President Debra A Kaden Senior Scientist which contain both the Investigators’ Robert M O’Keefe Vice President Geoffrey H Sunshine Senior Scientist Jane Warren Director of Science Annemoon MM van Erp Staff Scientist Report and the Review Committee’s Sally Edwards Director of Publications Terésa Fasulo Senior Administrative Assistant evaluation of the work’s scientific quality Jacqueline C Rutledge Director of Finance and Administration Gail A Hamblett Office and Contracts Manager and regulatory relevance. Richard M Cooper Corporate Secretary L Virgi Hepner Senior Science Editor Cristina I Cann Staff Scientist Jenny Lamont Science Copy Editor Aaron J Cohen Principal Scientist Francine Marmenout Senior Executive Assistant Maria G Costantini Principal Scientist Teresina McGuire Accounting Assistant STATEMENT Synopsis of Research Report 111 Concentrated Ambient Particles and Blood Coagulation in Rats INTRODUCTION exposed to filtered air. Due to the limited scope of the Several epidemiologic studies have shown an asso- study, however, the lack of a consistent effect is diffi- ciation between short-term increases in ambient par- cult to interpret. Factors that may have contributed to ticulate matter and short-term increases in morbidity the lack of effect in this study include the use of and mortality, especially in people with cardiovas- healthy animals, the time points evaluated, the lower cular disease. The biological mechanisms by which than expected concentration of ambient particulate particulate matter may affect cardiovascular events matter on exposure days, and the lack of concentration are not well understood, however. Dr Christine Nad- of smaller particles, where much of the particle mass ziejko of the New York University School of Medicine from mobile sources (a major source of particulate hypothesized that exposure of healthy rats to ambient matter) is found. In addition, animal studies generally particles may cause changes in blood coagulation use small numbers of individuals in comparison with parameters. The hypothesis that particulate matter epidemiology studies that investigate large popula- may exert its adverse health effects by altering blood tions, reducing the power to detect small changes. coagulation parameters is biologically relevant The blood coagulation system is complex with because clots may precipitate cardiac arrest, espe- many positive and negative feedback loops to main- cially in people with cardiovascular disease. The tain homeostasis. Thus the particulate matter expo- Health Effects Institute funded the animal study sure may have caused changes in parts of the described in this report to address this hypothesis. coagulation system that were not investigated in the current study but might be detected with other types APPROACH of measurements. For example, one could perform functional assays (such as platelet aggregation or clot- The investigators measured platelet number, blood ting time) or investigate endothelial aspects of clot cells counts, and levels of fibrinogen, thrombin-anti- formation. The lack of a consistent effect in the cur- thrombin complex, tissue plasminogen activator, rent study as well as other studies does not preclude plasminogen activator inhibitor, and factor VII. Rats that particulate matter exposure may affect coagula- were exposed to concentrated New York City particles tion under particular circumstances (for example, in or filtered air for 6 hours; blood samples were individuals with preexisting disease). Animal models obtained via an indwelling catheter before and after that exhibit increased clot formation or vascular exposure. A particle concentrator was used to deliver plaques may be more likely to show changes in blood concentrated particulate matter to the animals at a coagulation after being challenged with exposure to target concentration of 300 µg/m3, which was reached particulate matter. on 2 of 5 experimental days. The investigators used Some human controlled exposure and epidemio- concentrated particulate matter to increase the likeli- logic studies have reported changes in blood cell hood of finding an effect. counts, platelet counts, fibrinogen, and factor VII in relation to air pollution, but other human studies and RESULTS AND INTERPRETATION most animal studies have failed to find such changes. The investigators found no consistent differences No consistent pattern has emerged so far. To comple- in coagulation end points in animals exposed to con- ment

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