2000 Progress Report: Mechanism of PM-Induced Acute Health Effects

EPA Grant Number: R826244
Title: Mechanism of PM-Induced Acute Health Effects
Investigators:
Institution: New York University Medical Center
EPA Project Officer: Chung, Serena
Project Period: January 23, 1998 through January 22, 2001
Project Period Covered by this Report: January 23, 1999 through January 22, 2000
Project Amount: $600,799
RFA: Health Effects and Exposures to Particulate Matter and Associated Air Pollutants (1997) RFA Text |  Recipients Lists
Research Category: Air Quality and Air Toxics , Particulate Matter , Air , Health Effects

Objective:

The objective of this study is to determine the biological mechanism for systemic effects associated with acute exposure to ambient particulate matter (PM). We have hypothesized that inhaled PM causes immediate effects on the autonomic regulation of the cardiovascular system resulting in a stress response, and that the biological changes associated with this response can explain a substantial portion of the mortality associated with acute exposure to PM. Our preliminary studies have demonstrated that concentrated ambient PM induces a stress response in normal rats. We will determine whether environmentally relevant concentrations of PM cause a stress response and whether there is a threshold concentration below which PM does not cause acute cardiovascular changes. Moreover, because of epidemiologic evidence that PM-associated adverse effects may occur in those individuals with pre-existing illness, we also have hypothesized that concentrated ambient PM will produce these systemic effects at lower concentrations in an animal model of compromised health. Because of the confounding effects of gaseous co-pollutants on estimates of relative risk of morbidity and mortality attributable to PM exposure, we will test the hypothesis that ambient gases alter the stress response to inhaled PM.

Progress Summary:

During the previous reporting period, we demonstrated that: (1) the cardiovascular changes produced by exposure to concentrated ambient PM do not occur in rodents on all exposure days (suggesting that the adverse effects of PM may be influenced by the day-to-day variation in particle composition); (2) exposure to relatively high levels of concentrated ambient PM does not alter pulmonary function in guinea pigs; and (3) although lavage fluid parameters are not changed in mice exposed to concentrated ambient PM, cytokine mRNA expression levels are increased in lung tissue (collaboration with Dr. Mossman, University of Vermont). During the current period, we have concentrated our efforts on the effect of concentrated ambient PM and ambient gases on normal versus compromised and young versus old animals. In these experiments, we observed differences in the response of animals to environmentally relevant concentrations of concentrated ambient PM versus nitrogen dioxide, carbon monoxide, or sulfur dioxide. As in our previous work, we observed day-to-day variation in heart rate effects after exposure of young and old normal rats to concentrated ambient PM. In the old rats (18 months), however, we did observe a significant increase in sinus arrhythmias after exposure to approximately 175 g/m3 PM. Because these arrhythmias were observed in PM exposures but not after ambient gas exposures, this suggests that arrhythmias observed in epidemiology panel studies may be due to ambient PM and not gaseous pollutants. Moreover, we also observed a consistent increase in heart rate following a single 4-hour exposure of 12-month old spontaneously hypertensive rats to concentrated ambient PM. This increase in heart rate was not observed in old, spontaneously hypertensive rats exposed to 25 ppm carbon monoxide or 1 ppm nitrogen dioxide. Relevant to the objectives of our research project, our findings suggests that ambient particles have a more significant effect on the cardiovascular system of aged, spontaneously hypertensive rats at these exposure concentrations. To identify potentially susceptible individuals, therefore, future epidemiology panel studies should include people with a variety of cardiovascular diseases including hypertension.

Future Activities:

As determined to date, concentrated ambient PM appears to produce more adverse effects in old, spontaneously hypertensive rats than in normal rats. We will, therefore, focus our work on the possible adverse effects of PM in this animal model and examine the interaction between concentrated ambient PM and ambient gas exposure.


Journal Articles on this Report : 3 Displayed | Download in RIS Format

Other project views: All 9 publications 4 publications in selected types All 4 journal articles
Type Citation Project Document Sources
Journal Article Gordon T, Gerber H, Fang CP, Chen LC. A centrifugal particle concentrator for use in inhalation toxicology. Inhalation Toxicology 1999;11(1):71-87. R826244 (2000)
R826244 (Final)
R825268 (Final)
  • Abstract from PubMed
  • Abstract: Informa-Abstract
    Exit
  • Journal Article Gordon T, Reibman J. Cardiovascular toxicity of inhaled ambient particulate matter. Toxicological Sciences 2000;56(1):2-4. R826244 (1999)
    R826244 (2000)
    R826244 (Final)
    R827351 (Final)
    R827351C004 (2002)
    R827351C004 (Final)
  • Abstract from PubMed
  • Full-text: Oxford Journals-Full Text HTML
    Exit
  • Abstract: Oxford Journals-Abstract
    Exit
  • Other: Oxford Journals-Full Text PDF
    Exit
  • Journal Article Shukla A, Timblin C, BeruBe K, Gordon T, McKinney W, Driscoll K, Vacek P, Mossman BT. Inhaled particulate matter causes expression of nuclear factor (NF)-κB–related genes and oxidant-dependent NF-κB activation in vitro. American Journal of Respiratory Cell and Molecular Biology 2000;23(2):182-187. R826244 (1999)
    R826244 (2000)
    R826244 (Final)
  • Abstract from PubMed
  • Full-text: AJRCMB-Full Text HTML
    Exit
  • Abstract: AJRCMB-Abstract
    Exit
  • Other: AJRCMB-Full Text PDF
    Exit
  • Supplemental Keywords:

    particles, metals, ambient air, animal, mechanisms, mammalian., RFA, Health, Scientific Discipline, Air, particulate matter, Toxicology, Health Risk Assessment, Risk Assessments, Biochemistry, Environmental Monitoring, Atmospheric Sciences, co-factors, copollutant exposures, cardiopulmonary responses, inhalability, morbidity, cardiovascular vulnerability, dose response, air pollution, air sampling, biological mechanisms, cardiopulmonary mechanisms, chronic health effects, particulate exposure, Acute health effects, mortality

    Progress and Final Reports:

    Original Abstract
  • 1998
  • 1999 Progress Report
  • Final Report