2009 Progress Report: Assessing Toxicity of Local and Transported Particles Using Animal Models Exposed to CAPs

EPA Grant Number: R832416C003
Subproject: this is subproject number 003 , established and managed by the Center Director under grant R832416
(EPA does not fund or establish subprojects; EPA awards and manages the overall grant for this center).

Center: Harvard Particle Center
Center Director: Koutrakis, Petros
Title: Assessing Toxicity of Local and Transported Particles Using Animal Models Exposed to CAPs
Investigators: Godleski, John J. , Koutrakis, Petros
Institution: Harvard University
EPA Project Officer: Chung, Serena
Project Period: October 1, 2005 through September 30, 2010 (Extended to September 30, 2011)
Project Period Covered by this Report: August 1, 2008 through July 31,2009
RFA: Particulate Matter Research Centers (2004) RFA Text |  Recipients Lists
Research Category: Health Effects , Air

Objective:

The objective of this project is to differentiate the toxicological effects of locally emitted and transported particles.  To do so, short-term 5 hr animal exposures to concentrated ambient fine particles (CAPs) were conducted during the time periods of 5-10 am and 10:30 am-3:30 pm.  Starting inhalation exposures at 5 am, before significant vertical mixing takes place, captures particles predominantly from local sources, while, exposures starting about 10:30 am are relatively more enriched in transported particles.  Specific biologic outcomes reported in the third year report included breathing patterns, indicators of pulmonary and systemic inflammation, and in vivo oxidant responses in the heart and lung. In this report, we focus on assessment of blood pressure and heart rate over repeated early and late exposures. To control for circadian variations outcomes were assessed during both time periods, in relation to those of filtered air (sham) exposures. Animal exposures were characterized using continuous measurements of particle mass, size, number, and black carbon, as well as integrated measurements of particle mass, sulfate, elements, and organics. Strains of rats used include Spontaneously Hypertensive Rats (SHR), a sensitive model in many studies, and Wistar Kyoto (WKY), the strain control for SHR rats.
 
 The specific objectives of this project are:
 
• To differentiate the cardiovascular effects of locally emitted parti­cles from those of transported particles using normal animals, and;
 
• To determine whether spontaneously hypertensive rats, a geneti­cally susceptible population, have enhanced vascular responses to exposures of different particle sources as compared to normal ani­mals.

Progress Summary:

Early-late experiments: Spontaneously Hypertensive Rats (SHR) and Wistar Kyoto Rats (WKY) were exposed for 5 hours, 1 day a week for 32 weeks, in either time period (early morning or mid day) to con­centrated ambient particles (CAPs) from Boston air or to filtered air (n=32). Animals were implanted with DSI PA-C40 telemeters to monitor blood pressure and heart rate during exposure. Continuous respiratory data were collected using a whole body plethysmogra­phy system. Linear mixed models were used to assess differences in the blood pressure and respiratory outcome trajectories over the weeks due to rat species (WKY vs SHR), exposure (SHAM vs CAPs), time of day (AM vs PM), and the different levels of various exposure elements. The model specified either a linear or a quadratic form for weekly trend, and the interactions related to the changes in this weekly trend across the factors.
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 Early and late fine particle mass exposure concentrations were 424.83±184.8 and 447.18±125.6 μg/m³, respectively. The Table on this page includes all exposure characterization data.
 
The exposure was different in early morning compared to later in the day, but not as different as expected. Mass and particle number were similar. Black carbon and elemental car­bon were higher in the morning, but the difference did not reach statistical significance. Urban road dust related elements (Al, Mg, K, Pb, Ti, and Si were all significantly higher later in the day. Sulfur, as expected, was higher later in the day.
 
Biological Outcomes: For the SHR group there were differences for the quadratic time trend (p<0.01), and differences in the trend between early and late times of the day for heart rate, systolic, diastolic, mean and pulse pres­sure (p<0.001). There was no difference between CAPs and SHAM groups. For the WKY group, the quadratic time trend difference was significant for heart rate (p<0.0001). Systolic, diastolic, mean and pulse pressure linearly increased overtime (p<0.1). Univariate and multivariate assessment of responses to specific exposure compo­nents showed adverse effects on breathing pattern and cardiovascular parameters.
 
Breathing Pattern/Respiratory Changes: Diurnal differences in breathing patterns were present in both groups. The rapid shallow breathing pattern for WKY rats was related to the concentration of Vanadium (a marker of oil combustion). SHR rats showed an early/late exposure differ­ence that was associated with the concentration of Na, which may be considered as a marker of the exposure and not a marker for a specific source of pollution because many spring exposures were in­cluded in the data, which in Boston is a time for on-shore sea winds.
 
 
 
 
 Text Box: Diastolic BP overtime in SHR rats (AM left; PM right)
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Blood Pressure Changes: Systolic and diastolic BP in SH rats were much higher than in WKY rats. The overall change in BP parameters over time in the AM was different from PM. SH rats BP parameters in the morning initially increased then plateaued at very high diastolic and systolic levels with no enhancement with CAPs exposure. The SH rat BP parameters had a very different shape over-time in the PM, but also were very high. Both may indicate that BP levels were so high that they were beyond other influences. WKY rat BP increases were continuous over time and CAPs had a greater influence especially in the afternoon. This was related to road dust components as shown below.
 
 

Standardized regression coefficients for Diastolic BP for WKY rats in relationship to various tracer concentrations. *=p<0.05; **=p<0.01

 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


Journal Articles on this Report : 6 Displayed | Download in RIS Format

Other subproject views: All 14 publications 12 publications in selected types All 12 journal articles
Other center views: All 200 publications 194 publications in selected types All 194 journal articles
Type Citation Sub Project Document Sources
Journal Article Bartoli CR, Wellenius GA, Coull BA, Akiyama I, Diaz EA, Lawrence J, Okabe K, Verrier RL, Godleski JJ. Concentrated ambient particles alter myocardial blood flow during acute ischemia in conscious canines. Environmental Health Perspectives 2009;117(3):333-337. R832416 (2009)
R832416C003 (2009)
R832416C003 (Final)
  • Full-text from PubMed
  • Abstract from PubMed
  • Associated PubMed link
  • Full-text: EHP-Full Text PDF
  • Abstract: EHP-Abstract & Full Text HTML
  • Journal Article Bartoli CR, Wellenius GA, Diaz EA, Lawrence J, Coull BA, Akiyama I, Lee LM, Okabe K, Verrier RL, Godleski JJ. Mechanisms of inhaled fine particulate air pollution-induced arterial blood pressure changes. Environmental Health Perspectives 2009;117(3):361-366. R832416 (2008)
    R832416 (2009)
    R832416C003 (2009)
    R832416C003 (Final)
    R827353 (Final)
  • Full-text from PubMed
  • Abstract from PubMed
  • Associated PubMed link
  • Full-text: EHP-Full Text PDF
  • Abstract: EHP-Abstract & Full Text HTML
  • Journal Article Bartoli CRG, Godleski JJ. Blood flow in foreign-body capsules surrounding surgically implanted subcutaneous devices. Journal of Surgical Research 2010;158(1):147-154. R832416 (2009)
    R832416C003 (2009)
  • Full-text from PubMed
  • Abstract from PubMed
  • Associated PubMed link
  • Abstract: Journal of Surgical Research-Abstract
    Exit
  • Journal Article Fanning EW, Froines JR, Utell MJ, Lippmann M, Oberdorster G, Frampton M, Godleski J, Larson TV. Particulate Matter (PM) Research Centers (1999-2005) and the role of interdisciplinary center-based research. Environmental Health Perspectives 2009;117(2):167-174. R832416 (2009)
    R832416C003 (2009)
    R827351 (Final)
    R827352 (Final)
    R827353 (Final)
    R827354 (Final)
    R827355 (Final)
    R832415 (2010)
    R832415 (2011)
    R832415 (Final)
    R832415C003 (2011)
    R832415C004 (2011)
    R832415C005 (2011)
  • Full-text from PubMed
  • Abstract from PubMed
  • Associated PubMed link
  • Full-text: EHP-Full Text PDF
  • Abstract: EHP-Abstract and Full Text HTML
  • Journal Article Ghelfi E, Rhoden CR, Wellenius GA, Lawrence J, Gonzalez-Flecha B. Cardiac oxidative stress and electrophysiological changes in rats exposed to concentrated ambient particles are mediated by TRP-dependent pulmonary reflexes. Toxicological Sciences 2008;102(2):328-336. R832416 (2008)
    R832416 (2009)
    R832416C003 (2009)
    R827353 (Final)
  • Abstract from PubMed
  • Full-text: Toxicological Sciences-Full Text HTML
    Exit
  • Abstract: Toxicological Sciences-Abstract
    Exit
  • Other: Toxicological Sciences-Full Text PDF
    Exit
  • Journal Article Nikolov MC, Coull BA, Catalano PJ, Godleski JJ. Multiplicative factor analysis with a latent mixed model structure for air pollution exposure assessment. Environmetrics 2011;22(2):165-178. R832416 (2009)
    R832416 (Final)
    R832416C003 (2009)
    R832416C003 (Final)
  • Abstract: Wiley-Abstract
    Exit
  • Supplemental Keywords:

    concentrated air particles, acute cardiovascular effects, coarse particles, fine particles, vascular dysfunction, RFA, Health, Scientific Discipline, Air, particulate matter, Environmental Chemistry, Health Risk Assessment, Risk Assessments, ambient air quality, atmospheric particulate matter, chemical characteristics, human health effects, cardiovascular vulnerability, automobile exhaust, airborne particulate matter, chemical composition, biological mechanisms, biological mechanism , human exposure, mobile sources, ambient particle health effects, autonomic dysfunction, human health risk

    Relevant Websites:

    http://www.hsph.harvard.edu/epacenterexit EPA

    Progress and Final Reports:

    Original Abstract
  • 2006 Progress Report
  • 2007 Progress Report
  • 2008 Progress Report
  • 2010
  • Final Report

  • Main Center Abstract and Reports:

    R832416    Harvard Particle Center

    Subprojects under this Center: (EPA does not fund or establish subprojects; EPA awards and manages the overall grant for this center).
    R832416C001 Cardiovascular Responses in the Normative Aging Study: Exploring the Pathways of Particle Toxicity
    R832416C002 Cardiovascular Toxicity of Concentrated Ambient Fine, Ultrafine and Coarse Particles in Controlled Human Exposures
    R832416C003 Assessing Toxicity of Local and Transported Particles Using Animal Models Exposed to CAPs
    R832416C004 Cardiovascular Effects of Mobile Source Exposures: Effects of Particles and Gaseous Co-pollutants
    R832416C005 Toxicological Evaluation of Realistic Emission Source Aerosol (TERESA): Investigation of Vehicular Emissions