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Final 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: EPA Harvard Center for Ambient Particle Health Effects
Center Director: Koutrakis, Petros
Title: Differentiating the Roles of Particle Size, Particle Composition, and Gaseous Co-Pollutants on Cardiac Ischemia
Investigators: Godleski, John J. , Gonzales-Flecha, B. , Wellenius, Gregory
Institution: Harvard University
EPA Project Officer: Stacey Katz/Gail Robarge,
Project Period: June 1, 1999 through May 31, 2005 (Extended to May 31, 2006)
Project Amount: Refer to main center abstract for funding details.
RFA: Airborne Particulate Matter (PM) Centers (1999)
Research Category: Particulate Matter
Description:
Objective:Theme III: Biological Mechanisms/Dosimetry: Theme III focused upon mechanisms of cardiac vulnerability as a result of air pollution exposure. Many of our concentrated ambient particles (CAPs) animal toxicology and human panel studies have linked pulmonary and cardiovascular health outcomes to different particulate matter (PM) components such as trace metals, elemental carbon, sulfates and silicon (Batalha, et al., 2002; Clarke, et al., 2000; Saldiva, et al., 2002). Reanalysis of the Harvard Six Cities study provided strong evidence of increased toxicity associated with combustion-related PM from traffic and power plants compared to soil dust (Laden, et al., 2000).
The objectives of Theme III were to identify the particulate and gaseous air pollutants responsible for increased cardiac vulnerability as an adverse health effect and to define the biological mechanisms that lead to this outcome. As part of this theme, we specifically worked to: (1) identify the physical and chemical properties of particulate matter responsible for the observed adverse health effects; (2) determine whether gaseous co-pollutants exacerbate the effects of particles; (3) investigate the biological mechanisms by which particulate matter produces mortality and acute or chronic morbidity; and (4) examine particle deposition patterns and fate in the respiratory tract. These objectives were addressed in several areas of research that explored the components of air pollution that cause adverse health effects and the biological mechanisms that may lead to fatal outcomes. The projects under this theme built upon the findings from a number of our previous animal studies, which made it possible to explore and define both cardiac and pulmonary responses to inhaled fly ash and concentrated ambient particles (Killingsworth, et al., 1997).
To improve understanding of mechanisms, we developed and tested a model for investigating the effects of inhaled PM on arrhythmias and heart rate variability (HRV), a measure of autonomic nervous system activity, in rats with acute myocardial infarction (MI) (Wellenius, et al., 2002). Left-ventricular MI was induced in Sprague-Dawley rats by thermocoagulation of the left coronary artery; additional rats served as sham-operated controls. Diazepam-sedated rats were exposed (1h) to either residual oil fly ash (ROFA), black carbon (BC), or room air, 12–8 hours after surgery. Each exposure was immediately preceded and followed by a 1h exposure to room air (baseline and recovery periods, respectively). Lead II electrocardiograms were recorded. This rat model was also used in two additional studies, described below, evaluating effects of CAPs and CO on arrhythmias (Wellenius, et al., 2004; Wellenius, et al., 2006)
Summary/Accomplishments (Outputs/Outcomes):In the MI group, 41% of rats exhibited one or more premature ventricular complexes (PVCs) during the baseline period. Exposure to ROFA, but not to BC or room air, increased arrhythmia frequency in animals with pre-existing PVCs. Furthermore, MI rats exposed to ROFA, but not to BC or room air, decreased HRV. There was no difference in arrhythmia frequency or HRV among sham-operated animals (Wellenius, et al., 2002).
As ambient air pollution is a complex mixture of PM and gaseous pollutants such as carbon monoxide (CO), the effect of exposure to CO, alone or in combination with ambient PM, on arrhythmia incidence in the MI model was studied (Wellenius, et al., 2004). To evaluate the arrhythmogenic potential of ambient PM and CO, individually and together, left-ventricular myocardial infarction was induced in rats by thermocoagulation. Diazepam-sedated rats were exposed (1h) to either filtered air (n=43), CO (35 ppm, n=21), CAPs, mean concentration=523.1 μg/m3, n=58), or CAPs and CO (n=24), 12–18h after surgery. Each exposure was immediately preceded and followed by a 1h exposure to filtered air (baseline and recovery periods, respectively). The CO target dose of 35 ppm is related to the 1hr US National Ambient Air Quality Standard. Lead II electrocardiograms were recorded and heart rate and arrhythmia incidence were quantified. CO exposure alone and with CAPs reduced VPBs frequency by 60.4% (p=0.012) during the exposure period as compared to the filtered air group. This effect was modified by both infarct type and the frequency of VPBs at baseline, and was not mediated through changes in heart rate. CAPs exposure had no effect on VPB frequency overall, but led to a reduction in VPBs during the recovery period in animals with a high number of baseline VPBs, relative to the controls. This effect was likely mediated by a CAPs dose-dependent increase in heart rate. No significant interactions were observed between the effects of CO and CAPs.
Since recent studies suggest an association between PM2.5 and supraventricular arrhythmias (SVA), we evaluated this association in a rat model of acute MI—diazepam-sedated Sprague-Dawley rats with MI (Wellenius, et al., 2006). The animals were exposed for 1 h to either: (1) filtered air (n=16); (2) CAPs (mean=645.7 μg/m3, n=23); (3) carbon monoxide (CO; 35 ppm; n=19); or (4) CAPs and CO (n=24). Each exposure was immediately preceded and followed by a 1 hr exposure to filtered air (baseline and post-exposure periods, respectively). Surface electrocardiograms were recorded and the frequency of supraventricular premature beats was quantified. Among rats in the CAPS group, the probability of observing any SVA decreased from baseline to the exposure and post-exposure periods. This pattern was significantly different than that observed for the filtered air group during the exposure period (p=0.048) only. In the subset of rats with one or more SVA during the baseline period, the change in SVA rate from baseline to exposure period was significantly lower in the CAPs (p=0.04) and CO (p=0.007) groups only, as compared to the filtered air group. No significant effects were observed in the group simultaneously exposed to CAPs and CO. The results of this study do not support the hypothesis that exposure to ambient air pollution increases the risk or frequency of supraventricular arrhythmias.
Conclusions:These results underscore the usefulness of this model for elucidating the physiologic mechanisms of pollution-induced cardiovascular arrhythmias and contribute to defining the specific constituents of ambient particles responsible for arrhythmias. Inhalation of combustion-derived PM clearly exacerbates cardiac vulnerability following acute MI.
References:
Batalha JRF, Saldiva PHN, Clarke RW, Coull BA, Stearns RC, Lawrence J, Krishna Murthy GG, Koutrakis P, Godleski JJ. Concentrated ambient air particles induce vasoconstriction of small pulmonary arteries in rats. Environmental Health Perspectives 2002;110(12):1191-1197.
Clarke RW, Coull BA, Reinisch U, Catalano P, Killingsworth CR, Koutrakis P, Kavouras I., Krishna Murthy GG, Lawrence J, Lovett EG, Wolfson JM, Verrier RL, Godleski JJ. Inhaled concentrated ambient particles are associated with hematologic and bronchoalveolar lavage changes in canines. Environmental Health Perspectives 2000;108(12):1179-1187.
Killingsworth C, Alessandrini F, Murthy G, Catalano P, Paulauskis J, Godleski J. Inflammation, chemokine expression, and death in monocrotaline-treated rats following fuel oil fly ash inhalation. Inhalation Toxicology 1997;9:541-565.
Laden F, Neas L, Dockery D, Schwartz J. Association of fine particulate matter from different sources with daily mortality in six U.S. cities. Environmental Health Perspectives 2000;108(10):941-947.
Saldiva PH, Clarke RW, Coull BA, Stearns RC, Lawrence J, Koutrakis P, Suh H, Tsuda A, Godleski JJ. Acute pulmonary inflammation induced by concentrated ambient air particles is related to particle composition. American Journal of Respiratory and Critical Care Medicine 2002;165(12):1610-1617.
Wellenius GA, Batalha JR, Diaz EA, Lawrence J, Coull BA, Katz T, Verrier RL, Godleski JJ. Cardiac effects of carbon monoxide and ambient particles in a rat model of myocardial infarction. Toxicological Sciences 2004;80(2):367-376.
Wellenius GA, Coull BA, Batalha JRF, Diaz EA, Lawrence J, Godleski JJ. Effects of ambient particles and carbon monoxide on supraventricular arrhythmias in a rat model of myocardial infarction. Inhalation Toxicology 2006;18(14):1077-1082.
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;66:327-335.
Journal Articles on this Report: 4 Displayed | Download in RIS Format
| Other subproject views: | All 4 publications | 4 publications in selected types | All 4 journal articles |
| Other center views: | All 149 publications | 149 publications in selected types | All 148 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) |
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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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Wellenius GA, Batalha JRF, Diaz EA, Lawrence J, Coull BA, Katz T, Verrier RL, Godleski JJ. Cardiac effects of carbon monoxide and ambient particles in a rat model of myocardial infarction. Toxicological Sciences 2004;80(2):367-376. |
R827353 (Final) R827353C008 (Final) |
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Wellenius GA, Coull BA, Batalha JRF, Diaz EA, Lawrence J, Godleski JJ. Effects of ambient particles and carbon monoxide on supraventricular arrhythmias in a rat model of myocardial infarction. Inhalation Toxicology 2006;18(14):1077-1082. |
R827353 (Final) R827353C008 (Final) |
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, Air, Geographic Area, Scientific Discipline, Health, RFA, Susceptibility/Sensitive Population/Genetic Susceptibility, Molecular Biology/Genetics, Toxicology, Biology, Risk Assessments, Disease & Cumulative Effects, genetic susceptability, Microbiology, Epidemiology, air toxics, Children's Health, Atmospheric Sciences, Environmental Engineering, Environmental Microbiology, particulate matter, Environmental Chemistry, Environmental Monitoring, State, tropospheric ozone, ambient measurement methods, cardiopulmonary, risk assessment, exposure and effects, gaseous co-polutants, ambient air quality, cardiovascular disease, chronic effects, elderly, health effects, indoor air, indoor air quality, inhalation, Washington (WA), developmental effects, epidemelogy, lung cancer, respiratory disease, inhalation toxicology, co-pollutants, air quality, ambient air, cardiopulmonary response, indoor exposure, molecular epidemiology, assessment of exposure, cardiac ischemia, cardiopulmonary responses, human health risk, interindividual variability, monitoring, susceptibility, genetic susceptibility, particle exposure, toxics, epidemeology, air pollutants, human health effects, particulates, PM 2.5, respiratory, sensitive populations, biological response, ambient particle health effects, air pollution, ambient monitoring, children, inhaled, lung, stratospheric ozone, Utah (UT), Connecticut (CT), ambient air monitoring, chemical exposure, dosimetry, exposure, inhaled particles, pulmonary, human health, Illinois (IL), human susceptibility, environmental health hazard, particle chemical composition, biological mechanism , health risks, human exposure, Human Health Risk Assessment, particle size, pulmonary disease, Minnesota, Massachusetts (MA)
Relevant Websites:
http://www.hsph.harvard.edu/epacenter/epa_center_99-05/index.html
Progress and Final Reports:
1999 Progress Report
2000 Progress Report
2001 Progress Report
2002 Progress Report
2003 Progress Report
2004 Progress Report
Original Abstract
Main Center Abstract and Reports:
R827353 EPA Harvard Center for Ambient Particle Health Effects
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