2000 Progress Report: Effects of Particle-Associated Irritants on the Cardiovascular SystemEPA 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)
Project Period Covered by this Report: June 1, 1999 through May 31, 2000
RFA: Airborne Particulate Matter (PM) Centers (1999) RFA Text | Recipients Lists
Research Category: Air Quality and Air Toxics , Particulate Matter , Air
The objective of this research project is to examine the cardiovascular effects of gaseous co-pollutants, in response to recent epidemiological studies which suggest that co-pollutant gases contribute to the cardiovascular effects of particulate matter (PM). The physical and chemical properties of PM responsible for cardiovascular health effects are currently unknown. This project is closely coordinated with another project directed by Dr. Chen, also part of the New York University (NYU) Environmental Protection Agency (EPA) PM Center. The same animal models and biological endpoints are used in both studies. However, the two projects differ in the exposure atmospheres that are being examined, so as to test different hypotheses regarding the biologically active components of PM.
Identification of sensitive animal models and endpoints. Sensitive animal models and endpoints are needed to achieve our primary objective, to identify the biologically active components of PM. Human panel studies have reported an increase in arrhythmias in association with exposure to ambient PM. Therefore, there is a need for an animal model that not only has cardiac arrhythmias but that also has an increase in arrhythmia frequency with PM exposure. We implanted electrocardiogram (ECG) transmitters in a group of male F-344 rats (n = 12) aged 18 months. Baseline studies showed that at least half of these rats had spontaneous arrhythmias consisting of ectopic beats and delayed beats. We then developed protocols for arrhythmia identification and quantification. As described below, there was a statistically significant increase in the frequency of one type of arrhythmia in these rats following exposure to concentrated ambient PM.
Effects of concentrated ambient PM, ultrafine carbon particles, and SO2 on cardiac parameters in young and old rats. While concentrated ambient PM is the most realistic surrogate for particulate air pollution for use in controlled animal and human exposures, it is not enriched in ultrafine particles and it does not contain co-pollutant gases. We have done a series of experiments comparing the effects of concentrated ambient PM, laboratory-generated ultrafine carbon particles, and sulfur dioxide (SO2) in normal and aged rats. These studies were done to determine whether the effects of any of these exposures are similar to cardiac health effects reported in panel and epidemiology studies of particulate air pollution. We have exposed young and aged rats to concentrated ambient PM for 4 hours with ECG monitoring before, during, and up to 48 hours after exposure. Effects of PM exposure on heart rate are shown below:
|Rat age||PM Conc. (µg/m3)||Effect on Heart Rate||Time Course of Effect|
|Young||215||Decrease||6-23 hours post exposure|
|Young||60||Increase||1-24 hours post exposure|
|Old||200||Increase||18-25 hours post exposure|
|Old||161||Decrease||22-31 hours post exposure|
Significant effects on heart rate were seen in each exposure but the direction of the effect was variable. Heart rate effects occurred within the first 24 hours after exposure in young animals and lasted for 18-24 hours. Heart rate effects in aged rats were delayed in onset and shorter in duration. Exposure to ultrafine carbon at 1,500 and 500 micrograms (µg)/m3 significantly decreased heart rate in young rats and increased heart rate in old rats with a similar time course of effects as for PM exposure. Exposure to SO2 at a concentration of 1 part per million (ppm) had no significant effect on heart rate, even though exposures were repeated twice in young rats and four times in old rats (using a crossover design). Analysis of arrhythmias in aged rats showed that exposure to concentrated ambient PM, ultrafine carbon or SO2, had no significant effect on the frequency of ectopic beats. However, PM exposure significantly increased the frequency of sinus node arrythmias (skipped beats, prolonged pauses, and irregularly-irregular sinus rhythm). Surprisingly, an episode of prolonged ECG pause was also seen in two young rats after PM exposure, despite the fact that this arrhythmia is rare even in old rats.
Heart rate changes were seen following inhalation of particles (concentrated ambient PM, ultrafine carbon, and tobacco smoke), but not in response to the co-pollutant gases carbon monoxide, nitrogen dioxide, or SO2. However, only concentrated ambient PM (and not ultrafine carbon) was found to increase the frequency of arrhythmias. Spontaneously hypertensive rats and aged rats appear to be sensitive to inhaled ambient PM in terms of changes in heart rate and arrhythmia frequency, respectively.
A new group of spontaneously hypertensive rats has been implanted with blood pressure transmitters. We are developing protocols for arrhythmia analysis from blood pressure tracings to examine arrhythmia frequency in hypertensive rats. Aged F-344 rats are not currently available, but a group of 18-month old Sprague Dawley rats as well as a control group of young rats has been implanted with ECG transmitters. These three groups are currently being used in studies of fine and ultrafine sulfuric acid aerosols. Additional studies will be done with carbon particles and acid-coated carbon particles. This series of experiments will provide information on the relative roles of particle acidity, particle size, and physical structure in cardiac effects of PM.
Journal Articles:No journal articles submitted with this report: View all 5 publications for this subproject
Supplemental Keywords:particulate matter, PM, exposure, epidemiology, animal, rat, toxicology, organic irritant, cardiovascular, cardiac parameters, heart rate, electrocardiogram, ECG, arrythmia, hypertensive rat., RFA, Health, Scientific Discipline, PHYSICAL ASPECTS, Air, ENVIRONMENTAL MANAGEMENT, particulate matter, air toxics, Environmental Chemistry, Health Risk Assessment, Risk Assessments, Environmental Monitoring, Physical Processes, 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
Progress and Final Reports:Original Abstract
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