Grantee Research Project Results

1999 Progress Report: Differentiating the Roles of Particle Size, Particle Composition, and Gaseous Co-Pollutants on Cardiac Ischemia

EPA Grant Number: R827353C008
Subproject: this is subproject number 008 , established and managed by the Center Director under grant R827353
(EPA does not fund or establish subprojects; EPA awards and manages the overall grant for this center).
Center: Health Effects Institute (2015 - 2020)
Center Director: Greenbaum, Daniel S.
Title: Differentiating the Roles of Particle Size, Particle Composition, and Gaseous Co-Pollutants on Cardiac Ischemia
Investigators: Godleski, John J.
Current Investigators: Godleski, John J. , Gonzalez-Flecha, Beatriz , Wellenius, Gregory
Institution: Harvard University
EPA Project Officer: Chung, Serena
Project Period: June 1, 1999 through May 31, 2005 (Extended to May 31, 2006)
Project Period Covered by this Report: June 1, 1999 through May 31, 2000
Project Amount: Refer to main center abstract for funding details.
RFA: Airborne Particulate Matter (PM) Centers (1999) RFA Text |  Recipients Lists
Research Category: Particulate Matter , Air Quality and Air Toxics , Air

Objective:

This project is one of three projects under Theme III: Biological Mechanisms and Dosimetry of our proposal. The main aim of this study is to investigate the effects of concomitant gaseous co-pollutants, particle size, and particle composition using a dog cardiac ischemia model and our recently developed particle concentrator technologies. This project was intended to address Particulate Matter Research Topics 5, 8, and 9 identified by the National Research Council (NRC)-Assessing Hazardous Particulate Matter Components in Susceptible Population and Defining Mechanisms of Biological Response.

Progress Summary:

This project has had progress on all fronts. From the pollution mechanism viewpoint, we have concentrated on particle composition. However, we have worked on hardware and facilities to both develop and implement a coarse ambient particle concentrator. Although there has been progress in this area, we have not yet done any exposures with this concentrator. Similarly, we have not pursued the gaseous pollutant issue in the first year with the coronary disease models. A large number of studies was conducted in our laboratory using CAPs and ozone exposures at 0.3 ppm levels using mice. These were not Center-supported studies, but their results contributed to our decision-making process as to where to place our efforts. The mice studies did not yield impressive results. Statistically significant, but biologically minute, changes in pulmonary parameters were found. Therefore, we did not choose to make exposures to CAPs and gaseous pollutants a first year priority.

From the viewpoint of biological mechanisms, we have continued to make progress with coronary artery models as well as studies to define autonomic mechanisms in relationship to particle composition. We have carried out thoracic surgery for placement of balloon occluders on four canines. Exposures and analyses of these animals are in progress. We expect to combine these data with those previously collected to assess particle compositional issues.

We have completed studies of particle compositional assessment and the relationship to cardiac
autonomic nervous system changes in normal dogs. We find an activation of both the sympathetic and parasympathetic nervous system with CAPs exposure in dogs. The parasympathetic activation is in part pulmonary based, but even when controlling for the respiratory effect there is still a decrease in heart rate in normal dogs not explained by the respiratory effect. At the same time, heart rate variability changes indicate a concomitant increase in sympathetic activation. When related to the various factors making up the composition of ambient fine particulate, the observed cardiac changes relate best to traffic factors. Other factors appear to have little influence on the observed results.

Although cardiac effects mediated by the autonomic nervous system appear to be very important mechanisms, the role of blood constituents as mediators of cardiac effects is an equally viable hypothesis. We assessed hematological and coagulation factors before and after CAPs or sham exposures of canines. These studies are detailed in Clark, et al., 2000. Increased total peripheral white blood cell (WBC) counts, circulating neutrophils, and circulating lymphocytes were associated with increases in the aluminum (Al)/silicon (Si) factor. Increased circulating neutrophils were associated with the vanadium (V)/nickel (Ni) factor. Significant decreases in red blood cell counts and hemoglobin levels were correlated with the sulfur (S) factor. Variation in fibrinogen and platelets were not significantly associated with any factor. Hematological parameters were not associated with increases in total CAPs mass concentration. These data suggest that CAPs inhalation is associated with subtle alterations in systemic cell profiles and specific components of CAPs may be responsible for these biological responses.

Future Activities:

In the coming year, we expect to implement the coarse particle concentrator and carry out exposures using the rat model of cardiac ischemia. In these studies, we will directly compare the responses to coarse and fine particle fractions on the same days. We will measure heart rate, heart rate variability, and frequency of arrhythmia. Also in the coming year, we will continue our studies assessing ischemic responses of the canine in relationship to concentrated fine particles using surgical and pharmacologic approaches to define autonomic and inflammatory mechanisms. We also will use the rat model of myocardial infarction to determine if the arrhythmias seen in the most vulnerable periods after infarction are influenced by CAPs via autonomic or inflammatory mechanisms.

Journal Articles:

No journal articles submitted with this report: View all 4 publications for this subproject

Supplemental Keywords:

particulate matter, PM2.5, PM10, air pollutants, particulates, health effects, exposure, ambient particles, susceptibility, metals, public policy, biology, engineering, epidemiology, toxicology, environmental chemistry, monitoring., RFA, Health, Air, Scientific Discipline, Geographic Area, Susceptibility/Sensitive Population/Genetic Susceptibility, Risk Assessments, State, particulate matter, Biology, genetic susceptability, Environmental Chemistry, Epidemiology, tropospheric ozone, Microbiology, Environmental Microbiology, Molecular Biology/Genetics, Children's Health, Atmospheric Sciences, Disease & Cumulative Effects, Toxicology, air toxics, Environmental Engineering, Environmental Monitoring, air quality, health effects, health risks, Human Health Risk Assessment, indoor air quality, inhaled, sensitive populations, human health, epidemelogy, epidemeology, respiratory disease, cardiac ischemia, ambient monitoring, particle size, pulmonary disease, stratospheric ozone, particle chemical composition, biological mechanism , elderly, human exposure, indoor exposure, respiratory, risk assessment, Washington (WA), ambient air monitoring, lung cancer, biological response, gaseous co-polutants, co-pollutants, cardiopulmonary responses, chronic effects, dosimetry, lung, monitoring, pulmonary, susceptibility, genetic susceptibility, particulate exposure, chemical exposure, children, exposure, particulates, developmental effects, ambient particle health effects, air pollutants, ambient air, indoor air, inhaled particles, molecular epidemiology, Minnesota, Illinois (IL), toxics, environmental health hazard, inhalation toxicology, air pollution, ambient air quality, cardiopulmonary, cardiovascular disease, human health effects, human health risk, Connecticut (CT), assessment of exposure, human susceptibility, ambient measurement methods, cardiopulmonary response, inhalation, interindividual variability, PM 2.5, Massachusetts (MA), Utah (UT), particle exposure

Relevant Websites:

http://www.hsph.harvard.edu/epacenter/homeframe.htm Exit

Progress and Final Reports:

Original Abstract

2000 Progress Report

2001 Progress Report

2002 Progress Report

2003 Progress Report

2004 Progress Report

Final Report

Main Center Abstract and Reports:

R827353    Health Effects Institute (2015 - 2020)

Subprojects under this Center: (EPA does not fund or establish subprojects; EPA awards and manages the overall grant for this center).
R827353C001 Assessing Human Exposures to Particulate and Gaseous Air Pollutants
R827353C002 Quantifying Exposure Error and its Effect on Epidemiological Studies
R827353C003 St. Louis Bus, Steubenville and Atlanta Studies
R827353C004 Examining Conditions That Predispose Towards Acute Adverse Effects of Particulate Exposures
R827353C005 Assessing Life-Shortening Associated with Exposure to Particulate Matter
R827353C006 Investigating Chronic Effects of Exposure to Particulate Matter
R827353C007 Determining the Effects of Particle Characteristics on Respiratory Health of Children
R827353C008 Differentiating the Roles of Particle Size, Particle Composition, and Gaseous Co-Pollutants on Cardiac Ischemia
R827353C009 Assessing Deposition of Ambient Particles in the Lung
R827353C010 Relating Changes in Blood Viscosity, Other Clotting Parameters, Heart Rate, and Heart Rate Variability to Particulate and Criteria Gas Exposures
R827353C011 Studies of Oxidant Mechanisms
R827353C012 Modeling Relationships Between Mobile Source Particle Emissions and Population Exposures
R827353C013 Toxicological Evaluation of Realistic Emissions of Source Aerosols (TERESA) Study
R827353C014 Identifying the Physical and Chemical Properties of Particulate Matter Responsible for the Observed Adverse Health Effects
R827353C015 Research Coordination Core
R827353C016 Analytical and Facilities Core
R827353C017 Technology Development and Transfer Core