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Regional Cardiac Blood Flow With Air Particle Exposure

John J. Godleski1, Richard L. Verrier2, and Kazunori Okabe3
1Harvard School of Public Health, Boston, MA; 2Beth Israel Deaconess Medical Center,
Boston, MA; 3Brigham and Women’s Hospital, Boston, MA

EPA Grant Number: RD831917

Project Description:

Particulate air pollution is associated with cardiovascular morbidity and mortality in epidemiological studies. Our laboratory has pioneered the development of the ambient particle concentrator as a means to carry out inhalation toxicological assessments of responses to ambient particles in experimental animals. The most consistent and reproducible response to concentrated air particles (CAPs) from the urban air of Boston is the increase in severity of myocardial ischemia during acute coronary artery occlusion using canine models. The findings of these studies have a remarkable correspondence to the time course of myocardial infarction onset in relationship to air particulate levels in human epidemiological studies. The specific aims are: (1) to assess the mechanisms by which exposure to ambient particles exacerbates myocardial ischemia during acute coronary occlusion through assessment of regional myocardial blood flow; and (2) to evaluate the role of the autonomic nervous system in regulation of regional myocardial blood flow with coronary occlusion and exposure to ambient particles. Experimental approach: Our studies will employ the Harvard Ambient Particulate Con-centrator (HAPC), a device that can increase ambient particle concentrations up to 30x without changing the physical or chemical characteristics of the particles; (2) a typical urban aerosol; (3) large animal models of disease including myocardial ischemia in canines to simulate the condition of compromised humans with ischemic heart disease, the primary substrate for adult cardiac mortality. The animals will be chronically instrumented with catheters for microsphere injections and sampling as well as telemetry devices to monitor arterial blood pressure and EKG. Coronary blood flow and pressure will be assessed in animals with short-term coronary artery occlusion. Expected results: This proposal offers the unique application of novel techniques to improve understanding of the mechanisms whereby ambient particulate exerts deleterious influences on the heart and circulation. Enhanced ischemia has broad implications for cardiac morbidity and mortality and therefore studies of the physiologic mechanisms involved in relationship of this outcome to ambient particulate exposure are particularly important to EPA.

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