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Acute Exposure to Particulate Matter (PM) Alters Physiologic and Toxicologic Endpoints in a Rat Model of Heart Failure
Citation:
CARLL, A. P., N. HAYKAL-COATES, D. W. WINSETT, M. S. HAZARI, A. D. LEDBETTER, J. CALLAWAY, J. E. RICHARDS, D. L. COSTA, AND A. FARRAJ. Acute Exposure to Particulate Matter (PM) Alters Physiologic and Toxicologic Endpoints in a Rat Model of Heart Failure. Presented at Annual American Thoracic Society, San Diego, CA, May 15 - 20, 2009.
Impact/Purpose:
We used isoproterenol (ISO) to accelerate heart failure onset in SHHF rats. Exposure of ISO-pretreated rats to metal-sulfate particulate via nose-only inhalation caused physiologic changes and pulmonary inflammation ot seen in saline-pretreated rats that inhaled metal-sulfate.
Description:
Human exposure to ambient PM from fossil-fuel emissions is linked to cardiovascular disease and death. This association strengthens in people with preexisting cardiopulmonary diseases—especially heart failure (HF). We previously examined the effects of PM on HF by exposing Spontaneously Hypertensive Heart Failure (SHHF) rats to residual oil fly ash (ROFA) after accelerating HF onset via isoproterenol (ISO) infusion. In that study, rats were exposed to PM 2 wks after ISO treatment ceased, which was more than 1 wk after ISO-cessation had induced a 9-d period of hypotension. Epidemiological evidence suggests that effects would be more pronounced if exposure coincided with the HF-like hypotensive period. We hypothesized that PM exposure shortly after cessation of ISO treatment would cause greater cardiopulmonary injury. SHHF rats were infused with ISO (n=24; 1.0 mg/kg/d sc) or saline (n=23) via osmotic pump for 5 wks and then 5 d later exposed by nose-only inhalation for 4 h to either air or 580 µg/m3 of the PM2.5 fraction of a synthetic PM (dried salt solution, MSO4) similar in composition to a well-studied ROFA and consisting of Fe, Ni and V sulfates. In ISO-pretreated rats only, MSO4 decreased pulse pressure (an indirect indicator of cardiac output), decreased systolic and diastolic blood pressures, and increased QA interval (inversely related to myocardial contractility) during inhalation exposure and caused post-inhalation pulmonary inflammation significantly exceeding all other groups. Post-exposure effects (8 wks) on blood pressure, heart rate, and ECG are currently being assessed. This modified rat model of accelerated HF has enhanced sensitivity to PM exposure and may help elucidate the mechanisms of PM-induced HF exacerbation (Abstract does not reflect EPA policy; Supported by UNC/EPA CR83323601.)