MECHANISM OF PM-INDUCED ACUTE HEALTH EFFECTS (R826244)
8th Dec 2005, 07:12 GMT
The objective of this study is to determine the biological mechanism for systemic effects associated with acute exposure to ambient particulate matter (PM). We hypothesize that inhaled PM causes immediate effects on the autonomic regulation of the cardiovascular system resulting in a stress response and that the biological changes associated with this response can explain a substantial portion of the mortality associated with acute exposure to PM. Our preliminary studies have demonstrated that concentrated ambient PM induces a stress response in normal rats. We will determine whether environmentally relevant concentrations of PM cause a stress response and whether there is a threshold concentration below which PM does not cause acute cardiovascular changes. Moreover, because of epidemiologic evidence that PM-associated adverse effects may occur in those individuals with pre-existing illness, we also hypothesize that concentrated ambient PM will produce these systemic effects at lower concentrations in an animal model of compromised health. Because of the confounding effects of gaseous co-pollutants on estimates of relative risk of morbidity and mortality attributable to PM exposure, we will test the hypothesis that ozone and sulfur dioxide alter the stress response to inhaled PM. Finally, because there is uncertainty as to the relative contribution of indoor versus outdoor PM to adverse health effects, we will examine the dose-response curves for concentrated indoor and outdoor PM.
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