2011 Progress Report: Cardiometabolic, Autonomic, and Airway Toxicity of Acute Exposures to PM2.5 from Multipollutant Atmospheres in the Great Lakes Region

EPA Grant Number: R834797C002
Subproject: this is subproject number 002 , established and managed by the Center Director under grant R834797
(EPA does not fund or establish subprojects; EPA awards and manages the overall grant for this center).

Center: Great Lakes Air Center for Integrative Environmental Research
Center Director: Harkema, Jack
Title: Cardiometabolic, Autonomic, and Airway Toxicity of Acute Exposures to PM2.5 from Multipollutant Atmospheres in the Great Lakes Region
Investigators: Harkema, Jack , Fink, Greg , Wagner, James
Institution: Michigan State University
EPA Project Officer: Chung, Serena
Project Period: December 1, 2010 through November 30, 2015 (Extended to December 31, 2016)
Project Period Covered by this Report: January 1, 2011 through July 31,2011
RFA: Clean Air Research Centers (2009) RFA Text |  Recipients Lists
Research Category: Human Health , Air


Our objectives in Project 2 arise out of GLACIER’s overarching hypothesis that the major air pollutants, fine particulate matter (PM2.5) and ozone (O3), are 1) capable of eliciting multiple important adverse cardiometabolic health effects that are dependent on 2) the local multipollutant milieu, 3) an individual’s pre-existing cardiovascular (CV) and metabolic condition (susceptibility factors), and 4) the interactive toxicity of PM2.5 and O3 co-exposure. The goals of Project 2 are to determine the cardiovascular (CV), autonomic nervous system (ANS), and airway toxicity in rats acutely exposed to concentrated ambient PM2.5 (CAP) from distinct multipollutant atmospheres commonly found in the Great Lakes Region of the United States. Our studies are extensions of our previous findings that CAP-induced alterations in heart rate variability are dependent on specific PM2.5 emission sources in distinct locations in the Great Lakes Region. We will use a mobile air research facility (AirCARE 1) that is fully equipped with inhalation toxicology and atmospheric monitoring labs to conduct toxicology studies of rats exposed to CAP derived from real-world PM2.5 in three distinct locations dominated by industrial/urban, transported/regional, or near-roadway/residential emission sources. Blood pressure, heart rate, heart rate variability and direct measurements of autonomic nerve activity will be continuously monitored during CAP and/or O3 exposures in lean or obese rats with and without diet-induced facets of the cardiometabolic syndrome (CMS; hypertension, insulin resistance, endothelial dysfunction), respectively. Acute functional responses will be measured by radiotelemetry and will be correlated with specific PM constituents and their emission sources determined for the same highly resolved 30-minute timeframes, thereby making associations of exposure and health effects especially robust. Studies will feature novel real-time sympathetic nerve recordings during PM2.5 and/or O3 inhalation exposure. In addition, our project will highlight the unique integrative capabilities of our research team to link specific health cardiovascular effects in a sensitive obese population with PM content by a combined technological expertise that is unavailable elsewhere. Our GLACIER project will extend and complement the research of lean and obese human subjects (Project 1), conducted at the same exposure sites, by making invasive and prolonged measurements that could not be practically or ethically done in humans (e.g., repeated CAP exposures, continuous recordings of CV and autonomic nerve function, and microscopic examination of multiple organs for exposure-related pathology). Our acute animal studies also will overlap and integrate scientifically with the animal toxicology study of long-term multipollutant exposures in Project 3.

Progress Summary:

There have been no changes in study investigators or personnel, with the exception that Dr. Katryn Allen, from the University of Kansas Medical Center, was hired as a postdoctoral fellow for this project. Dr. Allen’s stipend, however, is being paid by the MSU Center for Integrative Toxicology, NIEHS funded training grant with no-cost to GLACIER. The project timeline and study protocol have been modified from the original design in order to better overlap with the aims of Projects 1 and 3 of GLACIER and to accord with the theme of investigating the health effects of air pollution mixtures in a multipollutant context. During Years 1-2, we now will perform our first acute animal inhalation studies at our urban industrial site (Dearborn, MI). In these studies, rats on normal or a high fructose (HF)-diet will be exposed to fine CAP with or without O3, O3 alone, or filtered air (controls) for 9 days, 8 h/day, and then sacrificed 24-hours after the last exposure day. Acute cardiovascular responses (e.g., blood pressure, heart rate, heart rate variability) will be measured by radiotelemetry during the exposures and will be correlated with specific PM2.5 constituents and their emission sources determined for the same highly resolved 30-minute timeframes as outlined in the original project plan. Tissue and fluid samples will be taken at necropsy from a wide-range of targeted organs and later analyzed for biochemical, molecular, and morphometric alterations related to the CMS. Novel measurements of real-time autonomic nerve activity during inhalation exposures are planned for studies in Year 2 to allow for specific details in the protocol to be worked out through pilot studies in Year 1. Two 9-day inhalation exposures to CAP and O3 will be completed in July and August with most of the planned data analyses being completed by the end of the year. Rats for these studies have been on normal and HF-diets for 8 weeks prior to the start of the multipollutant inhalation exposures that began on July 25, 2011, at the Dearborn, MI site. In Years 3 and 4 of our project, similar animal inhalation studies will be conducted at our rural transported pollution site in Dexter, MI. Nine-day inhalation exposures to fine and coarse CAP (with and without O3) will be performed in Years 3 and 4, respectively. The acute cardiovascular responses to coarse and fine CAP in rats on normal or HF-diets will be closely compared will those identified in human subjects similarly exposed to CAP in Project 1. 

Future Activities:

All aspects of the study protocol now are proceeding per the modified study design outlined above. We anticipate completing our Dearborn (industrial multipollutant atmosphere) exposure studies by the end of Year 2 and starting our acute animal toxicology studies at our Dexter rural site (transported multipollutant atmosphere) in Year 3 and continuing through Year 4. Based on our results from studies in Years 1-4, and those from studies in Projects 1 and 3, we will either extend our acute rat inhalation studies in Year 5 to either urban sites in Columbus, OH (Project 3) or conduct long-term inhalation exposures of mice in Dearborn (or Dexter) using protocols outlined in Project 3. 

Journal Articles:

No journal articles submitted with this report: View all 73 publications for this subproject

Supplemental Keywords:

Scientific Discipline, Air, ENVIRONMENTAL MANAGEMENT, air toxics, Health Risk Assessment, Biochemistry, Biology, Risk Assessment, ambient air quality, particulate matter, aerosol particles, susceptible populations, acute cardiovascualr effects, human exposure, physiology, cardiopulmonary, cardiotoxicity, human health

Relevant Websites:

http://greatlakesairresearchcenter.org/Exit EPA Disclaimer

Progress and Final Reports:

Original Abstract
  • 2012 Progress Report
  • 2013 Progress Report
  • 2014 Progress Report
  • 2015 Progress Report
  • 2016 Progress Report
  • Final Report

  • Main Center Abstract and Reports:

    R834797    Great Lakes Air Center for Integrative Environmental Research

    Subprojects under this Center: (EPA does not fund or establish subprojects; EPA awards and manages the overall grant for this center).
    R834797C001 Cardiometabolic Effects of Exposure to Differing Mixtures and Concentrations of PM2.5 in Obese and Lean Adults
    R834797C002 Cardiometabolic, Autonomic, and Airway Toxicity of Acute Exposures to PM2.5 from Multipollutant Atmospheres in the Great Lakes Region
    R834797C003 Long Term Metabolic Consequences of Exposures to Multipollutant Atmospheres in the Great Lakes Region