Grantee Research Project Results
2003 Progress Report: Differentiating the Roles of Particle Size, Particle Composition, and Gaseous Co-Pollutants on Cardiac Ischemia
EPA Grant Number: R827353C008Subproject: 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, 2003 through May 31, 2004
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:
The main objective of this research project is to investigate the effects of concomitant gaseous co-pollutants, particle size, and particle composition.
This is one of 10 projects funded by the Center. The progress for the other nine projects is reported separately (see reports for R827353C001 through R827353C007, and R827353C009 through R827353C011).
Progress Summary:
To date, a large number of animal exposure studies have been completed. These studies have been totally or partially funded by the Center. In Year 5 of the project, our efforts have included completing experiments, data analysis, presenting results at meetings, and preparing manuscripts.
During the last year, we have focused our efforts on completing a complex experiment on the effects of concentrated air particles (CAPs) and carbon monoxide (CO) on arrhythmia incidence in a rat model of myocardial infarction. These results recently were presented at the Annual Meeting of the American Thoracic Society, and a manuscript detailing the results was accepted for publication in Toxicological Sciences (Rhoden, et al., 2004). We previously have shown that inhalation exposure to combustion-derived particulate matter (PM) increases the incidence of ventricular arrhythmias in rats with a recent myocardial infarction (Wellenius, et al., 2002). It is unknown, however, whether exposure to ambient PM would elicit the same response. Additionally, numerous studies have found an association between short-term increases in ambient CO levels and increased risk of cardiovascular morbidity (Burnett, et al., 1997; Morris, et al., 1995; Schwartz, 1997; Schwartz and Morris, 1995; Yang, et al., 1998) and mortality (Hoek, et al., 2001; Mar, et al., 2000). Ambient levels of CO may confound or modify the PM-arrhythmia association observed in epidemiologic studies, but this hypothesis has not been evaluated in a controlled setting. Accordingly, the goal of this study was to examine the cardiac effects of exposure to ambient PM and CO, individually and in combination, in a rat model of myocardial infarction.
To evaluate these effects, left-ventricular myocardial infarction was induced
in Sprague-Dawley rats by thermocoagulation. Diazepam-sedated rats were exposed
(1 hour) to either filtered air (n = 40), CO (35 ppm, n = 19), CAPs (median
concentration = 350.5 µg/m3, n = 53),
or CAPs and CO (CAPs median concentration = 318.2 µg/m3,
n = 23), 12-18 hours after surgery. Each exposure immediately was preceded
and followed by a 1-hour exposure to filtered air (pre-exposure
and post-exposure periods, respectively). The CO target dose of 35 ppm is related
to the 1-hour U.S. National Ambient Air Quality Standard. Surface electrocardiograms
were recorded, and heart rate and arrhythmia incidence were quantified. Contrary
to our initial hypothesis, we found that CO exposure reduced ventricular premature
beat (VPB) frequency by 60.4 percent (p = 0.012) during the exposure period
compared to control animals exposed to filtered air. This effect was modified
by both the infarct type (transmural versus subepicardial) and the number of
pre-exposure VPBs (< 4 versus 4) and was not mediated through changes
in heart rate.
Overall, CAP exposure increased VPB frequency during the exposure period, but this effect did not reach statistical significance. The increase in arrhythmia incidence was not significantly associated with CAP mass concentration, CAP number concentration, or the mass concentration of any specific component of CAPs that we measured. This effect was modified by the number of pre-exposure VPBs. Overall, CAPs had no effect on heart rate, but CAPs were associated with increased heart rate in specific subgroups. No significant interactions were observed between the effects of CO and CAPs. We conclude that in this animal model, the cardiac responses to CO and CAPs are distinctly different. In epidemiologic studies, it is often suggested that cardiac effects attributed to ambient PM actually represent effects of ambient CO instead. The results of this study suggest that it is unlikely that arrhythmogenic effects associated with ambient PM exposure actually are attributable to ambient CO instead.
Although less common, atrial arrhythmias also were observed in these experiments. Therefore, we have begun to evaluate the effects of CAPs and CO on atrial arrhythmias using these data. Preliminary results indicate that atrial responses to CAPs and CO also are distinctly different.
Additionally, we have begun collecting new experimental data to evaluate the effect of CAPs and ozone, individually and in combination, on cardiac arrhythmias. This new series of experiments overcomes some of the limitations of our past experiments by using radiotelemetry devices to monitor the electrocardiogram (as opposed to surface electrodes). This change in approach allows us to avoid the use of a sedative and provides for longer exposure times and pre- and post-exposure monitoring.
Future Activities:
We will continue to investigate the effects of concomitant gaseous co-pollutants, particle size, and particle composition. In addition, we will continue to: (1) evaluate the effects of CAPs and CO on atrial arrhythmias using the data collected; and (2) collect new experimental data to evaluate the effect of CAPs and ozone, individually and in combination, on cardiac arrhythmias.
Journal Articles on this Report : 2 Displayed | Download in RIS Format
| Other subproject views: | All 4 publications | 4 publications in selected types | All 4 journal articles |
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| Other center views: | All 207 publications | 205 publications in selected types | All 204 journal articles |
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Wellenius GA, Saldiva PHN, Batalha JRF, Krishna Murthy GG, Coull BA, Verrier RL, Godleski JJ. Electrocardiographic changes during exposure to residual oil fly ash (ROFA) particles in a rat model of myocardial infarction. Toxicological Sciences 2002;66(2):327-335. |
R827353 (Final) R827353C008 (2001) R827353C008 (2002) R827353C008 (2003) R827353C008 (Final) |
Exit Exit Exit |
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Wellenius GA, Coull BA, Godleski JJ, Koutrakis P, Okabe K, Savage ST, Lawrence JE, Krishna Murthy GG, Verrier RL. Inhalation of concentrated ambient air particles exacerbates myocardial ischemia in conscious dogs. Environmental Health Perspectives 2003;111(4):402-408. |
R827353 (Final) R827353C008 (2001) R827353C008 (2002) R827353C008 (2003) R827353C008 (Final) |
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Supplemental Keywords:
exposure, health effects, biology, toxicology, environmental chemistry, monitoring, air pollutants, air pollution, air quality, ambient air, ambient air monitoring, ambient air quality, ambient monitoring, ambient particle health effects, ambient particles, animal inhalation study, exposure assessment, biological mechanism, biological response, cardiopulmonary, cardiopulmonary response, cardiovascular disease, chemical exposure, environmental health hazard, exposure and effects, health risks, human exposure, human health, human health effects, human health risk, indoor air quality, indoor exposure, inhalation, inhalation toxicology, inhaled particles, particle exposure, particulate exposure, particulates, pulmonary, pulmonary disease, respiratory, respiratory disease, risk assessment., 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 exposureRelevant Websites:
https://cfserver.hsph.harvard.edu/cfdocs/eer/epa/ Exit
Progress and Final Reports:
Original AbstractMain 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
The perspectives, information and conclusions conveyed in research project abstracts, progress reports, final reports, journal abstracts and journal publications convey the viewpoints of the principal investigator and may not represent the views and policies of ORD and EPA. Conclusions drawn by the principal investigators have not been reviewed by the Agency.