Extramural Research
Presentation Abstract
Grantee Research Project Results
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.