Grantee Research Project Results
2000 Progress 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: Health Effects Institute (2015 - 2020)
Center Director: Greenbaum, Daniel S.
Title: Differentiating the Roles of Particle Size, Particle Composition, and Gaseous Co-Pollutants on Cardiac Ischemia
Investigators: Godleski, John J.
Current Investigators: Godleski, John J. , Gonzalez-Flecha, Beatriz , Wellenius, Gregory
Institution: Harvard University
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, 2000 through May 31, 2001
Project Amount: Refer to main center abstract for funding details.
RFA: Airborne Particulate Matter (PM) Centers (1999) RFA Text | Recipients Lists
Research Category: Air Quality and Air Toxics , Particulate Matter , Air
Objective:
This project is one of three projects under Theme III: Biological Mechanisms and Dosimetry of our proposal. The main aim of this study is to investigate the effects of concomitant gaseous co-pollutants, particle size, and particle composition using a dog cardiac ischemia model and our recently developed particle concentrator technologies.Progress Summary:
We have developed and tested simplified variations in the protocol of the dog ischemia model to establish a response pattern that could be used in studies of pharmacologic interventions to define mechanistic effects. In the general ischemia model protocol, a 5-minute conditioning occlusion with a 20-minute recovery period is followed by a second and sometimes third 5-minute occlusion. Previously, we had done the conditioning and one occlusion prior to an exposure of concentrated air particles (CAPs), and a third occlusion after the exposure. These occlusions took place on the third day of a 3-day, 6 hours/day CAPs or sham exposure protocol with cross-over the following week. Using 3-dimensional electrocardiograms, a positive response pattern in the same dog under CAPs conditions compared to sham is illustrated (see Figure 1). In this example, the second occlusion in the CAPs dog has a higher ST segment and higher T wave than the same dog in her second occlusion as sham. The third occlusion in the CAPs dog has an earlier onset, higher ST segments, and higher T-waves than either the second CAPs or either sham occlusions.This suggests that there may be carry-over of effect from the previous day's CAPs exposure as well as augmentation of the effect on the third day. However, this pattern was not consistent from week to week. As in many other of our laboratory experiments with CAPs, it appeared that composition may be the determining factor in this variability, but this protocol was not designed to carry out large numbers of experiments to pursue this issue, nor was it capable of testing the hypothesis of carry-over of effects from day to day.
Therefore, a simplified version of the dog ischemia model protocol was developed. This also involves two dogs studied at the same time. The first day, both dogs are sham exposed and have one conditioning and one test occlusion after exposure. The second day, one dog is exposed to CAPs and her chamber-mate is sham exposed with conditioning and test occlusions following exposure. The dogs cross-over for the third day's exposure so that the dog who was sham exposed the day before, now receives CAPs, and occlusions are done after exposure. The fourth day both dogs are sham exposed with occlusions again following exposure. Outcomes assessed include time and magnitude of ST segment elevation, T-wave morphology, heart rate, and heart rate variability. Preliminary analyses indicate that: (1) there appears to be a carry-over of effect after the first day of CAPs exposure in the ST-segment changes; (2) this carry-over does not extend to the second day post-exposure; (3) there is day-to-day variability in the magnitude of the responses; and (4) this protocol is more suited to assess large numbers of exposure days and hence, useful to assess compositional variability as a cause of the magnitude of change in response. Twenty CAPs exposure days have been completed using five different dogs. Compositional analysis of the exposure is under way, as is detailed electrocardiogram analyses.
In addition, we have developed a rat model of acute myocardial infarction to study the effects of CAPs on ischemia induced arrhythmias. In these studies, a myocardial infarction is surgically induced in rats. On the following day, the rats are given either a particle or sham exposure and the electrocardiogram is continuously monitored before, during, and after exposure. Studies using this approach have used fly ash, carbon black, and CAPs to assess arrhythmias. Both fly ash and CAPs exposures significantly increase the number of premature ventricular contractions (PVCs) in animals that have PVCs in their baseline. Sham and carbon black exposures do not increase PVCs. This appears to be a sensitive model of cardiac effects of CAPs and we now are using this approach to study the influence of gaseous co-pollutants on the CAPs effect. Studies are beginning with carbon monoxide and will be followed by ozone. This rat model also appears to be useful for interventional pharmacologic experiments to determine the pathophysiologic mechanism(s) triggering the observed arrhythmias. These studies will begin in the coming year.
Future Activities:
For the dog ischemia model, we will complete the compositional analysis of the exposure and the detailed electrocardiogram analyses within the next few months so that it can be determined if this protocol can be used for interventional mechanistic studies. Using the rat model, we will begin studies with carbon monoxide, followed by ozone to study the effects of CAPs on ischemia induced arrhythmias.Journal Articles:
No journal articles submitted with this report: View all 4 publications for this subprojectSupplemental Keywords:
particulate matter, PM2.5, PM10, air pollutants, particulates, health effects, exposure, ambient particles, susceptibility, metals, public policy, biology, engineering, epidemiology, toxicology, environmental chemistry, monitoring., RFA, Health, Scientific Discipline, Air, Geographic Area, particulate matter, Toxicology, air toxics, Environmental Chemistry, Epidemiology, State, Risk Assessments, Microbiology, Susceptibility/Sensitive Population/Genetic Susceptibility, Environmental Microbiology, Disease & Cumulative Effects, Environmental Monitoring, Children's Health, genetic susceptability, tropospheric ozone, Atmospheric Sciences, Molecular Biology/Genetics, Biology, Environmental Engineering, ambient air quality, health effects, monitoring, particle size, risk assessment, sensitive populations, chemical exposure, interindividual variability, molecular epidemiology, particulates, Minnesota, air pollutants, exposure and effects, lung, stratospheric ozone, PM 2.5, ambient air monitoring, health risks, cardiopulmonary responses, indoor exposure, human health effects, ambient air, developmental effects, epidemelogy, respiratory disease, exposure, pulmonary disease, biological response, ambient measurement methods, Utah (UT), ambient monitoring, children, air pollution, particle exposure, biological mechanism , Human Health Risk Assessment, lung cancer, Massachusetts (MA), Washington (WA), human exposure, chronic effects, inhalation, pulmonary, ambient particle health effects, cardiopulmonary response, particulate exposure, susceptibility, assessment of exposure, Illinois (IL), elderly, inhaled, inhalation toxicology, epidemeology, environmental health hazard, human susceptibility, indoor air, Connecticut (CT), gaseous co-polutants, cardiopulmonary, human health, indoor air quality, inhaled particles, cardiac ischemia, respiratory, toxics, co-pollutants, genetic susceptibility, air quality, dosimetry, cardiovascular disease, human health riskRelevant Websites:
http://www.hsph.harvard.edu/epacenter/homeframe.htm
Progress and Final Reports:
Original AbstractMain Center Abstract and Reports:
R827353 Health Effects Institute (2015 - 2020) 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
The perspectives, information and conclusions conveyed in research project abstracts, progress reports, final reports, journal abstracts and journal publications convey the viewpoints of the principal investigator and may not represent the views and policies of ORD and EPA. Conclusions drawn by the principal investigators have not been reviewed by the Agency.
Project Research Results
- Final Report
- 2004 Progress Report
- 2003 Progress Report
- 2002 Progress Report
- 2001 Progress Report
- 1999 Progress Report
- Original Abstract
4 journal articles for this subproject
Main Center: R827353
207 publications for this center
204 journal articles for this center