CARDIOVASCULAR VULNERABILITY TO PARTICULATE EXPOSURE

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Epidemiologic associations between particulate air pollution and cardiovascular hospitalization and mortality have been found, but little is understood about the physiologic mechanisms by which humans respond to particulate exposure. Canines respond to concentrated fly-ash and/or fine particles with ECG repolarization abnormalities including ST segment abnormalities, T-wave alternans (an index of susceptibility to sudden death), and changes typical of both hyperadrenergic activity and vagally mediated effects, depending on the underlying status of the dogs. In susceptible adults we propose to examine whether particle exposure results in similar changes, particularly in measures of autonomic function, myocardial conductance, repolarization, and irritability. Outdoor and indoor PM2~5, PM10, CO, O3, NO2, 502 and temperature will be considered as exposures. A Boston community-based panel of 50 active adults 60-90 yr of age will be recruited and evaluated over two 3-month summer periods; this panel study will be repeated in a higher pollution community in two subsequent summers. Once per week for l2 weeks the participants will receive supine and upright blood pressure, oximetry and continuous ECG Holter monitoring for a 25 minute period (5 minutes of rest supine, 5 minutes of standing upright, 5 minutes of exercise, 5 minutes of recovery and 5 minutes of slow breathing.) Electrophysiologic outcomes will include ECG repolarization abnormalities, ventricular premature beats, measures of heart rate variability; PR and QT intervals. Modification or response by underlying disease and medication will be considered. A second study of >800 outpatients will assess the associations between particulate exposure and cardiopulmonary exercise data routinely collected during repeated exercise in two Boston cardiac and pulmonary rehabilitation units. These will enable us to assess whether particulate exposure is associated with physiologic changes predictive of cardiovascular vulnerability and sudden death in active humans who are susceptible on the basis of age or disease.