Final Report: Effects of Particle-Associated Irritants on the Cardiovascular System

EPA Grant Number: R827351C006
Subproject: this is subproject number 006 , established and managed by the Center Director under grant R827351
(EPA does not fund or establish subprojects; EPA awards and manages the overall grant for this center).

Center: EPA NYU PM Center: Health Risks of PM Components
Center Director: N/A
Title: Effects of Particle-Associated Irritants on the Cardiovascular System
Investigators: Nadziejko, Christine
Institution: New York University School of Medicine
EPA Project Officer: Chung, Serena
Project Period: June 1, 1999 through May 31, 2005 (Extended to May 31, 2006)
RFA: Airborne Particulate Matter (PM) Centers (1999) RFA Text |  Recipients Lists
Research Category: Air Quality and Air Toxics , Particulate Matter , Air

Objective:

The effect of particulate matter (PM) on the cardiovascular system is an increasingly important public health issue. However, the physical and/or chemical properties of PM responsible for these serious health effects are currently unknown. The questions are: 1) What are the biologically active components of PM? 2) What are the mechanisms by which PM affects the cardiovascular system? and 3) What are the sensitive subpopulations? These three questions are inextricably intertwined. Any hypothesis about a mechanism of cardiovascular effects rests on some assumptions that a certain type of constituent of PM is the culprit.

This research focused on particle-associated irritants based in part on the time course of effects reported in recent epidemiological studies. There is consistent evidence from times-series studies that the lag time between elevated levels of PM2.5 and increases in cardiovascular-related hospital admissions and death is very short, i.e. one day or less. There is one well-studied physiological mechanism that is consistent with rapid effects of PM on both cardiovascular and pulmonary function, namely stimulation of irritant receptors in the respiratory tract. Irritant receptor activation involves a bimolecular reaction between a protein receptor in the lung and an agonist, which triggers a rapid increase in intracellular calcium (Ca++) leading to activation of nerve fibers that send impulses to the central nervous system. Signals from the central nervous system then cause slowing of respiration and changes in blood pressure and heart rate via neural reflex pathways. The stereotypical response to an inhaled irritant is an immediate change in respiratory rate and heart rate, which returns to normal soon after exposure stops.

The objectives of this project were: 1) to examine the time course of effects of concentrated ambient PM (CAPs) on cardiovascular function in sensitive animals to establish the biological plausibility of short lag times between PM exposure and cardiovascular effects; and 2) to expose rats (both normal rats and rat models of cardiac disease) to sulfuric acid aerosols, a known irritant found in PM, to determine whether irritant aerosols cause cardiovascular changes consistent with the adverse health effects of PM. Exposure to carbon black particles was used as a non-irritant control.

Summary/Accomplishments (Outputs/Outcomes):

We examined the effects of various PM air pollutants on rats with surgically implanted electrocardiogram (ECG) and blood pressure (BP) transmitters to determine whether inhaled PM causes immediate physiological effects. Spontaneously hypertensive rats (SHR) with BP transmitters (which measure BP, heart rate and respiratory rate) were exposed to CAPS for 4 hrs. The SHR were also exposed to fine and ultrafine sulfuric acid aerosols because acid is one of the components of PM that could potentially activate irritant receptors and cause effects during exposure. Young and old (> 20 months) Sprague Dawley (SD) rats with ECG transmitters (which measure heart rate and core temperature) were exposed to fine and ultrafine acid aerosols and to resuspended carbon black. Inhalation of CAPS by the SHR caused a striking decrease in respiratory rate that was apparent soon after the start of exposure, and that stopped when exposure to CAPS ceased. The decrease in respiratory rate was accompanied by a decrease in heart rate. Exposure of the same SHR to fine particle size sulfuric acid aerosol also caused a significant decrease in respiratory rate similar to the effects of CAPS. Ultrafine acid had the opposite effect on respiratory rate in SHR as CAPS. In both old and young SD rats, inhalation of fine acid aerosol caused an immediate increase in temperature (compared to air-exposed rats) that ceased when exposure stopped. Ultrafine acid caused an immediate decrease in heart rate and temperature during exposure in young SD rats and no significant effect on old SD rats. Carbon black inhalation had no significant effect on heart rate or temperature during exposure in either old or young rats. This study showed that inhalation of ambient PM and acid aerosols have immediate effects on cardiopulmonary function during exposure. The pattern of the response to inhaled PM is consistent with activation of irritant receptors in the respiratory tract. Telemetry data from these experiments is being analyzed to determine whether significant cardiovascular effects from PM or acid persist after exposure stops.

Conclusions:

Overall, we did more than 50 experiments exposing rats to CAPS, irritant aerosols, particulate matter surrogates and even some irritant gases. Every experiment involved monitoring of cardiovascular functional data in an air-exposed and pollutant-exposed group before exposure, during exposure and for 48-72 hrs exposure. We did extensive exploratory data analysis while experiments were being performed and solved a number of issues related to quantifying telemetric data. However, it was apparent that there was no suitable statistical method for determining whether there was a significant difference between the treated and control groups because the onset and duration of the effects were unknown. Drs. Nadziejko and Chen, in collaboration with Dr. Jing-Shiang Hwang, a visiting scientist (and statistician) in the New York University (NYU) PM Center, and Dr. Arthur Nadas, a mathematical statistician in the Department of Environmental Medicine, developed a simple but powerful method of analyzing repeated measures data when the time course of the effect is not known a priori. This method, which is called the Fishing License method, has been published and used to analyze all of the telemetry data performed in the PM Center.

Technical Report:

Long Version of Final Report (PDF) (2 pp, 23.5 K, About PDF)


Journal Articles on this Report : 5 Displayed | Download in RIS Format

Other subproject views: All 5 publications 5 publications in selected types All 5 journal articles
Other center views: All 111 publications 100 publications in selected types All 88 journal articles
Type Citation Sub Project Document Sources
Journal Article Nadziejko C, Fang K, Nadziejko E, Narciso SP, Zhong M, Chen LC. Immediate effects of particulate air pollutants on heart rate and respiratory rate in hypertensive rats. Cardiovascular Toxicology 2002;2(4):245-252. R827351 (2003)
R827351 (Final)
R827351C005 (2001)
R827351C005 (2002)
R827351C005 (Final)
R827351C006 (2003)
R827351C006 (Final)
  • Abstract from PubMed
  • Abstract: SpringerLink-Abstract
    Exit
  • Journal Article Nadziejko C, Fang K, Chen LC, Gordon T, Nadas A. Quantitative analysis of cardiac data from rats monitored by telemetry: reducing within-and between-animal variability. Cardiovascular Toxicology 2002;2(4):237-244. R827351 (2003)
    R827351 (Final)
    R827351C005 (2002)
    R827351C005 (Final)
    R827351C006 (2003)
    R827351C006 (Final)
  • Abstract from PubMed
  • Abstract: SpringerLink-Abstract
    Exit
  • Journal Article Nadziejko C, Fang K, Narciso S, Zhong M, Su WC, Gordon T, Nadas A, Chen LC. Effect of particulate and gaseous pollutants on spontaneous arrhythmias in aged rats. Inhalation Toxicology 2004;16(6-7):373-380. R827351 (2003)
    R827351 (Final)
    R827351C005 (Final)
    R827351C006 (2003)
    R827351C006 (Final)
  • Abstract from PubMed
  • Abstract: Taylor and Francis-Abstract
    Exit
  • Journal Article Nadziejko C, Chen LC, Nadas A, Hwang JS. The 'Fishing License' method for analysing the time course of effects in repeated measurements. Statistics in Medicine 2004;23(9):1399-1411. R827351 (2003)
    R827351 (Final)
    R827351C005 (Final)
    R827351C006 (2003)
    R827351C006 (Final)
  • Abstract from PubMed
  • Abstract: Wiley Online - Abstract
    Exit
  • Journal Article Narciso SP, Nadziejko E, Chen LC, Gordon T, Nadziejko C. Adaptation to stress induced by restraining rats and mice in nose-only inhalation holders. Inhalation Toxicology 2003;15(11):1133-1143. R827351 (2001)
    R827351 (Final)
    R827351C005 (2002)
    R827351C005 (Final)
    R827351C006 (2003)
    R827351C006 (Final)
  • Abstract from PubMed
  • Abstract: Taylor and Francis-Abstract
    Exit
  • Supplemental Keywords:

    sulfur dioxide, particle, surface reactions, absorption, adsorption, heart rate variability, cardiac function,, RFA, Health, PHYSICAL ASPECTS, Scientific Discipline, Air, ENVIRONMENTAL MANAGEMENT, particulate matter, Environmental Chemistry, Health Risk Assessment, air toxics, Risk Assessments, Physical Processes, Environmental Monitoring, Atmospheric Sciences, Risk Assessment, ambient air quality, atmospheric particulate matter, particulates, atmospheric particles, chemical characteristics, toxicology, ambient air monitoring, acute cardiovascular effects, airborne particulate matter, environmental risks, exposure, epidemelogy, Sulfur dioxide, air pollution, aerosol composition, atmospheric aerosol particles, human exposure, PM, exposure assessment

    Relevant Websites:

    Long Version of Final Report (PDF) (2 pp, 23.5 K, About PDF)
    http://www.med.nyu.edu/environmental/ exit 

EPA
    https://www.epa.gov/research-grants/

    Progress and Final Reports:

    Original Abstract
  • 1999
  • 2000 Progress Report
  • 2001
  • 2002
  • 2003 Progress Report
  • 2004

  • Main Center Abstract and Reports:

    R827351    EPA NYU PM Center: Health Risks of PM Components

    Subprojects under this Center: (EPA does not fund or establish subprojects; EPA awards and manages the overall grant for this center).
    R827351C001 Exposure Characterization Error
    R827351C002 X-ray CT-based Assessment of Variations in Human Airway Geometry: Implications for Evaluation of Particle Deposition and Dose to Different Populations
    R827351C003 Asthma Susceptibility to PM2.5
    R827351C004 Health Effects of Ambient Air PM in Controlled Human Exposures
    R827351C005 Physicochemical Parameters of Combustion Generated Atmospheres as Determinants of PM Toxicity
    R827351C006 Effects of Particle-Associated Irritants on the Cardiovascular System
    R827351C007 Role of PM-Associated Transition Metals in Exacerbating Infectious Pneumoniae in Exposed Rats
    R827351C008 Immunomodulation by PM: Role of Metal Composition and Pulmonary Phagocyte Iron Status
    R827351C009 Health Risks of Particulate Matter Components: Center Service Core
    R827351C010 Lung Hypoxia as Potential Mechanisms for PM-Induced Health Effects
    R827351C011 Urban PM2.5 Surface Chemistry and Interactions with Bronchoalveolar Lavage Fluid (BALF)
    R827351C012 Subchronic PM2.5 Exposure Study at the NYU PM Center
    R827351C013 Long Term Health Effects of Concentrated Ambient PM2.5
    R827351C014 PM Components and NYC Respiratory and Cardiovascular Morbidity
    R827351C015 Development of a Real-Time Monitoring System for Acidity and Soluble Components in Airborne Particulate Matter
    R827351C016 Automated Real-Time Ambient Fine PM Monitoring System