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TEMPORAL ASSOCIATION BETWEEN PULMONARY AND SYSTEMIC EFFECTS OF PARTICULATE MATTER IN HEALTHY AND CARDIOVASCULAR COMPROMISED RATS
Kodavanti, U P., M. Schladweiler, A Ledbetter, R. Hauser, D. C. Christiani, J K. McGee, J. R. Richards, AND D L. Costa. TEMPORAL ASSOCIATION BETWEEN PULMONARY AND SYSTEMIC EFFECTS OF PARTICULATE MATTER IN HEALTHY AND CARDIOVASCULAR COMPROMISED RATS. JOURNAL OF TOXICOLOGY AND ENVIRONMENTAL HEALTH. Taylor & Francis, Inc., Philadelphia, PA, 65(20):1545-1569, (2002).
Temporal association between pulmonary and systemic effects of particulate matter in healthy and cardiovascular compromised rats
Urmila P. Kodavanti, Mette C. Schladweiler, Allen D. Ledbetter, Russ Hauser*, David C. Christiani*, John McGee, Judy R. Richards, Daniel L. Costa
Pulmonary Toxicology Branch, Experimental Toxicology Division, National Health and Environmental Effects Research Laboratory, Office of Research and Development, U.S. Environmental Protection Agency, Research Triangle Park, NC, and *Harvard School of Public Health, Boston, MA
Running title: PM-Induced Systemic Effects in Hypertensive Rats
Correspondence: Urmila P. Kodavanti, Ph.D.
Pulmonary Toxicology Branch, MD 82
Experimental Toxicology Division
National Health and Environmental Effects Research Laboratory
U.S. Environmental Protection Agency
Research Triangle Park, NC 27711
The research described in this article has been reviewed by the National Health and Environmental Effects Research Laboratory, U.S. Environmental Protection Agency and approved for publication. Approval does not signify that the contents necessarily reflect the views and the policies of the Agency nor does mention of trade names or commercial products constitute endorsement or recommendation for use.
The authors wish to thank Mr. James Lehmann (US EPA) for intratracheal instillation and for coordinating LPS analysis, and Mr. Donald L. Doerfler (US EPA) for statistical evaluation of the data. We thank Dr. Sarah Gardner, (North Carolina State University, Raleigh, NC) for her assistance in plasma analysis and Mr. Malory Maceiver of the University of North Carolina Hospitals, Chapel Hill, NC for blood analysis. We also thank Drs. Linda S. Birnbaum (US EPA), Kent Pinkerton (UC Davis, CA) and Jane Gallagher (US EPA) for their critical review of the manuscript.ABSTRACT
Exposure to particulate matter (PM) has been associated with increased morbidity and mortality among individuals with cardiovascular disease. It is hypothesized that systemic alterations occur concurrent to pulmonary injury/inflammation, and contribute to cardiac events in compromised hosts. We explored this hypothesis using a rat model for human hypertension and cardiovascular disease (Spontaneously Hypertensive; SH), and normotensive Wistar Kyoto (WKY) rats. SH and WKY rats (12-13 wks old) were exposed either intratracheally (IT; 0.0, 1.0 or 5.0 mg/kg in saline) or nose-only (15 mg/m3x6h/dx3d/wkx1, 2 or 4 wks) to combustion source residual oil fly ash (ROFA) with low metal content, and examined 1, 2 or 4 days later. Bronchoalveolar lavage fluid (BALF) albumin and neutrophils increased (SH WKY) at day 1 following ROFA IT. With inhalation exposure, both strains experienced progressive histological lung damage and increases in BALF albumin and neutrophils during 1 to 4 wks (SH>WKY). Acute lung injury from ROFA IT was temporally associated with increases in plasma fibrinogen in both strains, but only the SH rats responded to the acute 1 wk ROFA inhalation. Longer-term (2 or 4 wks) ROFA caused progressive lung injury (SH>WKY), but did not sustain the increase in fibrinogen. BALF glutathione increased in a similar temporal fashion as fibrinogen, however, only WKY rats demonstrated this response. There was a small but consistent decrease in blood lymphocytes and an increase in blood neutrophils in SH rats exposed to ROFA acutely. In conclusion, acute PM exposure can provoke an acute systemic thrombogenic response associated with pulmonary injury/inflammation and oxidative stress in cardiovascular compromised rats. This evidence is consistent with greater cardiovascular events during acute PM episodes in compromised humans.
Key words: Spontaneously hypertensive rat, particulate matter, systemic response, oxidative stress, plasma fibrinogen
Record Details:Record Type: DOCUMENT (JOURNAL/PEER REVIEWED JOURNAL)
Organization:U.S. ENVIRONMENTAL PROTECTION AGENCY
OFFICE OF RESEARCH AND DEVELOPMENT
NATIONAL HEALTH AND ENVIRONMENTAL EFFECTS RESEARCH LABORATORY
EXPERIMENTAL TOXICOLOGY DIVISION
PULMONARY TOXICOLOGY BRANCH