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CONCENTRATED AMBIENT PARTICULATES (CAPS) STUDIES TO ADDRESS SOURCE-ATTRIBUTED EFFECTS ON CARDIOPULMONARY FUNCTION
Impact/Purpose:
These studies will improve the database upon which the effects of particles on cardiovascular function can be attributed to specific components of particulate matter (PM), and will help define the sources of PM most strongly linked to those effects. In addition, they will address the issue of susceptibility by assessing the effects of CAPs on cardiovascular function in rats with compromised cardiopulmonary function.
Description:
Studies of ambient particulate matter (PM) in several venues around the world have shown consistent health impacts vis-a-vis mortality and morbidity. However, recent studies have reported varied and sometimes disparate outcomes with respect to observed effects on cardiopulmonary function, specifically on electrocardiographic endpoints. Animal studies have demonstrated a generally coherent impact on cardiac function at high doses of PM, with the greatest effects seen following exposure to combustion source emissions or associated metal constituents. We hypothesize that these discrepancies may be due to differences in the PM from the various sources studied. That is, the gross composition of CAPs samples is generally consistent across most urban venues, but the composition ratios of the various components seem to vary characteristically in relation to regional sources. Thus, a series of studies has been undertaken to more directly address the potential linkages between source-attributed exposures and cardiopulmonary responses, with primary endpoints focusing on cardiac function (ECG analyses and blood pressure). The spontaneously hypertensive (SH) rat was selected as a model for these studies because of its sensitivity to the irritancy of residual oil fly ash. A series of studies of Concentrated Ambient Particulates (CAPs) will be undertaken in the Summer of 2002 to test several hypotheses. Protocol 1. Animals with implanted telemeters will undergo a single 4-hour exposure to CAPs. Telemetered cardiac data will be monitored and collected throughout the exposure period and periodically for about 10 weeks. Electrocardiographic analyses will conducted during and after exposure, along with periodic assessments of ventilatory function. PM samples from the exposures will undergo thorough compositional analyses for inclusion into statistical models modified for source attribution studies (e.g., principal component analyses, mass balance) in an effort to ascribe any effects with PM mass, composition, and related source derivation. Protocol 2. A cohort of SH rats will be exposed to CAPs for 4 hours/day for 2-3 days/week for ~10 weeks. Electrocardiographic analyses will be conducted during and between exposures, along with periodic assessments of ventilatory function. Protocol 3. The monocrotaline (MCT) rat model of pulmonary vasculitis has been used with relative success as a model of unusual (if varied) sensitivity to ROFA (and in one case CAPs). Due to the progressive nature of the MCT-induced disease process, it is possible to study animals at various "stages" of disease severity. Thus, we will examine the effect of varying degrees of disability as a risk factor for CAPs-related adverse effects. Rats will be implanted with ECG / temperature radiotransmitters, after which they will treated with 50 mg/kg of MCT to induce a gradual injury over three to four weeks. At approximately 12 and 24 days post-MCT, separate groups of rats will be exposed to CAPs for 4 hours/day ? 3 days. Radiotelemetry parameters (HR, ECG, and body temperature) will be monitored throughout the treatment period, beginning prior to MCT injection and continuing through exposure to CAPs. The rats will be killed after exposure and assessed for degree of disease (lung and heart weights, serum chemistries, BAL cells and protein). CAPs filter samples will be assayed and compared with the health data in the context of the source-attribution study described above.