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Final Report: Effects of Concentrated Ambient Particles on the Cardiac and Pulmonary Systems of Dogs
EPA Grant Number: R828112C091Subproject: this is subproject number 091 , established and managed by the Center Director under grant R828112
(EPA does not fund or establish subprojects; EPA awards and manages the overall grant for this center).
Center: Health Effects Institute
Center Director: Greenbaum, Daniel S.
Title: Effects of Concentrated Ambient Particles on the Cardiac and Pulmonary Systems of Dogs
Investigators: Godleski, John J.
Institution: Harvard School of Public Health
EPA Project Officer: Katz, Stacey
Project Period: April 1, 2000 through March 31, 2005
RFA: Health Effects Institute (1996)
Research Category: Particles and Diesel Engine Exhaust , Public/Private Partnership Center
Description:
Objective:Epidemiology studies have indicated that short-term exposure to low-level increases in particulate matter is associated with an increase in morbidity and daily mortality, particularly in individuals with cardiopulmonary conditions. A plausible biologic mechanism linking low-level particle exposure and pathophysiologic effects has not been established, however. Assessing the effects of particulate matter in appropriate animal models is important to learning how particulate matter may exert adverse health effects. The Health Effects Institute funded the study described in this report as part of a research program to reduce this information gap. Summary/Accomplishments (Outputs/Outcomes):
Dr John Godleski and colleagues at Harvard School of Public Health conducted an exploratory study to test the effects of particulate matter exposure in dogs, which share many features of the human cardiovascular system. The investigators hypothesized that particulate matter might affect the animals? cardiac function, leading to arrhythmia, and might induce inflammatory responses and changes in pulmonary mechanical measurements. To maximize possible effects, they used a device to concentrate particles up to 30 times their level in ambient Boston air and exposed dogs to these concentrated ambient particles (CAPs) via inhalation. The investigators physically and chemically identified components of the CAPs and tested their effects in 12 dogs, in 6 of which they also induced a coronary occlusion to simulate human coronary artery disease. They evaluated the effects of CAPs on electrocardiographic (ECG) wave patterns and performed a sophisticated analysis of each dog?s ECG to measure possible effects of particulate matter on other electrical properties of the heart: heart rate variability, which is influenced by the involuntary nervous system, and T wave alternans, a change in the heart beat pattern. These two are among the measures currently used to predict further heart problems in humans with cardiovascular disease, but they have not been established as predictive parameters in normal humans or other species. The investigators also assessed whether changes in respiratory parameters or inflammatory responses were associated with CAPs exposure.
The most biologically and clinically significant finding was that in dogs with induced coronary occlusion, CAPs affected one of the major ECG signs of myocardial ischemia in humans, known as elevation of the ST segment. CAPs-exposed animals showed a shortened time to ST segment elevation and an increased magnitude of the ST segment compared to controls. These findings suggest what may be a plausible mechanism to explain PM?s effects on individuals with cardiopulmonary conditions: exposure to particulate pollution may make patients with ischemic heart disease more susceptible to developing serious cardiac effects. If substantiated in larger groups of animals, the evidence may help to explain the previously described association between increased particulate pollution and cardiopulmonary morbidity and mortality. Animals with an induced coronary occlusion also showed other changes in cardiac and respiratory parameters after exposure to CAPs.
The investigators also reported that normal dogs showed CAPs-induced changes in heart rate variability and average heart rate (which fluctuated widely from day to day during the course of the study), decreases in T wave alternans, and changes in respiratory parameters such as breathing rates and air flow rates. They did not identify whether the variability in responses was due to day-to-day fluctuation of a specific component of the particulate mixture. In addition, the investigators reported that CAPs had little or no effect on inflammatory mediators, suggesting that changes in cardiac and pulmonary responses occurred in the absence of significant airway inflammation.
The investigators interpreted their findings to indicate that CAPs influenced the nervous system?s control of the normal dog?s heart but did not necessarily induce arrhythmia. This interpretation may be reasonable, but the statistical approach the investigators used to identify changes in heart rate variability is not clearly applicable to the small number of dogs tested. In addition, it is not apparent whether it is appropriate to extrapolate these results to humans because the human and dog cardiovascular systems differ in some critical features. Furthermore, the clinical significance of changes in heart rate variability or T wave alternans in normal dogs, or in humans who do not have preexisting heart disease, is currently unknown.
Because Godleski and colleagues tested only a small number of animals, confirmation of the findings both in animals with impaired cardiac function and in normal animals is required in larger studies. Studies of effects in humans, such as those currently underway at HEI, are also expected to provide information about the possible effects of particulate matter on the heart.
Supplemental Keywords:Air, ambient air quality, air toxics, epidemiology, health effects, particulate matter, biochemistry, motor vehicle emissions, diesel exhaust, animal models, mortality, disease. , Air, Scientific Discipline, Health, RFA, Toxicology, Risk Assessments, Health Risk Assessment, air toxics, Biochemistry, particulate matter, Environmental Chemistry, mobile sources, exposure and effects, ambient air quality, cardiovascular disease, coronary artery disease, inhalation, dogs, inhalation toxicology, diesel exhaust, environmental health effects, automobiles, emissions, human health risk, lung inflammation, lung injury, air pollutants, engines, human health effects, particulates, motor vehicles, ambient particle health effects, air pollution, inhalability, inhaled, lung, human health, human exposure, PM, animal model
Progress and Final Reports:
Original Abstract
Main Center Abstract and Reports:
R828112 Health Effects Institute
Subprojects under this Center:
(EPA does not fund or establish subprojects; EPA awards and manages the overall grant for this center).
R828112C042 Does Inhalation of Methanol Vapor Affect Human Neurobehavior?
R828112C043 Human Responses to Nitrogen Dioxide
R828112C044 The Role of Inflammation in Ozone-Induced Lung Injury
R828112C045 How Does Exercise Affect the Dose of Inhaled Air Pollutants?
R828112C046 How Do Chemicals in Diesel Engine Exhaust Damage DNA?
R828112C047 Effect of Nitrogen Dioxide on Bacterial Respiratory infection
in Mice
R828112C048 Effects of Ozone Exposure on Airway Epithelium
R828112C049 Inhalation of Aldehydes and Effects on Breathing
R828112C050 Does Ozone Cause Precancerous Changes in Cells?
R828112C051 Effects of Formaldehyde on Human Airway Epithelial Cells Exposed in a Novel Culture System
R828112C052 Carbon Monoxide and Cardiac Arrhythmias
R828112C053 Effects of Formaldehyde and Particle-Bound Formaldehyde on Lung Macrophage Functions
R828112C054 Mechanisms for Protecting Lung Epithelial Cells Against Oxidant Injury
R828112C055 Relationship of Nitropyrene-Derived DNA Adducts to Carcinogenesis
R828112C056 Particle Trap Effects on Heavy-Duty Diesel Engine Emissions
R828112C057 Carbon Monoxide and Atherosclerosis
R828112C058 Nitrogen Dioxide and Respiratory Illness in Children
R828112C059 Noninvasive Methods for Measuring Ventilation in Mobile Subjects
R828112C060 Oxidant Air Pollutants and Lung Cancer: An Animal Model
R828112C061 Detection of Carcinogen-DNA Adducts: Development of New Methods
R828112C062 Effects of Carbon Monoxide on Heart Muscle Cells
R828112C063 Development of Personal Ozone Samplers: Three Approaches
R828112C064 Development of Biomarkers to Monitor Carcinogen Exposure
R828112C065 Effects of Prolonged Ozone Inhalation on Collagen Structure and Content in Rat Lungs
R828112C065II Prolonged Ozone Exposure and the Contractile Properties of Isolated Rat Airways
R828112C065III Changes in Complex Carbohydrate Content and Structure in Rat Lungs Caused by Prolonged Ozone Inhalation
R828112C065IV Genetic Control of Connective Tissue Protein Synthesis After Prolonged Ozone Inhalation
R828112C065V Pulmonary Function Alterations in Rats After Chronic Ozone Inhalation
R828112C065VII Prolonged Ozone Exposure Leads to Functional and Structural Changes in the Rat Nose
R828112C065VIII - IX Studies of Changes in Lung Structure and Enzyme Activities
in Rats After Prolonged Exposure to Ozone
R828112C065X An Innovative Approach to Analyzing Multiple Experimental Outcomes: A Case Study of Rats Exposed to Ozone
R828112C065XI The Consequences of Prolonged Inhalation of Ozone on Rats:
An Integrative Summary of the Results of Eight Collaborative Studies
R828112C066 Interactive Effects of Nitropyrenes in Diesel Exhaust
R828112C067 Detection of Formaldehyde–DNA Adducts: Development of New Methods
R828112C068I Comparison of the Carcinogenicity of Diesel Exhaust and Carbon Black in Rat Lungs
R828112C068II An Investigation of DNA Damage in the Lungs of Rats Exposed to Diesel Exhaust
R828112C068III No Evidence For Genetic Mutations Found In Lung Tumors From Rats Exposed To Diesel Exhaust or Carbon Black
R828112C069 Noninvasive Determination of Respiratory Ozone Absorption: The Bolus-Response Method
R828112C070 The Effects of Inhaled Oxidants and Acid Aerosols on Pulmonary Function
R828112C071 Biochemical Consequences of Ozone Reacting with Membrane Fatty Acids
R828112C072 DNA Mutations in Rats Treated with a Carcinogen Present in Diesel Exhaust
R828112C073 Developmental Neurotoxicity of Inhaled Methanol in Rats
R828112C074 Methanol Distribution in Non Pregnant and Pregnant Rodents
R828112C075 Is Increased Mortality Associated with Ozone Exposure in Mexico City?
R828112C076 Effects of Fuel Modification and Emission Control Devices on Heavy-Duty Diesel Engine Emissions
R828112C077 Metabolic Studies in Monkeys Exposed to Methanol Vapors
R828112C078 Effects of Ozone on Pulmonary Function and Airway Inflammation in Normal and Potentially Sensitive Human Subjects
R828112C079 Improvement of a Respiratory Ozone Analyzer
R828112C080 Mechanism of Oxidative Stress from Low Levels of Carbon Monoxide
R828112C081 Long-Term Exposure to Ozone: Development of Methods to Estimate Past Exposures and Health Outcomes
R828112C082 Effects of Ambient Ozone on Healthy, Wheezy, and Asthmatic Children
R828112C083 Daily Changes in Oxygen Saturation and Pulse Rate Associated with Particulate Air Pollution and Barometric Pressure
R828112C084 Evaluation of The Potential Health Effects of the Atmospheric Reaction Products of Polycyclic Aromatic Hydrocarbons
R828112C085 Mechanisms of Response to Ozone Exposure: The Role of Mast Cells in Mice
R828112C086 Statistical Methods for Epidemiologic Studies of the Health Effects of Air Pollution
R828112C087 Development of New Methods to Measure Benzene Biomarkers
R828112C088 Alveolar Changes in Rat Lungs After Long-Term Exposure to Nitric Oxide
R828112C089 Effects of Prenatal Exposure to Inhaled Methanol on Nonhuman Primates and Their Infant Offspring
R828112C090 A Pilot Study of Potential Biomarkers of Ozone Exposure
R828112C091 Effects of Concentrated Ambient Particles on the Cardiac and Pulmonary Systems of Dogs
R828112C092 Cancer, Mutations, and Adducts in Rats and Mice Exposed to Butadiene and Its Metabolites
R828112C093 Effects of Concentrated Ambient Particles in Rats and Hamsters: An Exploratory Study
R828112C094I The National Morbidity, Mortality, and Air Pollution Study: Methods and Methodologic Issues
R828112C094II The National Morbidity, Mortality, and Air Pollution Study: Morbidity and Mortality from Air Pollution in the United States
R828112C095 Association of Particulate Matter Components with Daily Mortality and Morbidity in Urban Populations
R828112C096 Acute Pulmonary Effects of Ultrafine Particles in Rats and Mice
R828112C097 Identifying Subgroups of the General Population That May Be Susceptible to Short-Term Increases in Particulate Air Pollution
R828112C098 Daily Mortality and Fine and Ultrafine Particles in Erfurt, Germany
R828112C099 A Case-Crossover Analysis of Fine Particulate Matter Air Pollution and Out-of-Hospital Sudden Cardiac Arrest
R828112C100 Effects of Mexico City Air on Rat Nose
R828112C101 Penetration of Lung Lining and Clearance of Particles Containing Benzo[a]pyrene
R828112C102 Metabolism of Ether Oxygenates Added to Gasoline
R828112C103 Characterization and Mechanisms of Chromosomal Alterations Induced by Benzene in Mice and Humans
R828112C104 Acute Cardiovascular Effects in Rats from Exposure to Urban Ambient Particles
R828112C105 Genetic Differences in Induction of Acute Lung Injury and Inflammation in Mice
R828112C106 Effects on Mice of Exposure to Ozone and Ambient Particle Pollution
R828112C107 Emissions from Diesel and Gasoline Engines Measured in Highway Tunnels