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Electrocardiographic, hemodynamic, and biochemical responses to acute particulate matter (PM) exposure in aged heart failure-prone rats
Citation:
Carll, A. P., M. S. HAZARI, N. HAYKAL-COATES, D. W. WINSETT, C. LAMB, J. H. Richards, D. L. COSTA, AND A. FARRAJ. Electrocardiographic, hemodynamic, and biochemical responses to acute particulate matter (PM) exposure in aged heart failure-prone rats. Presented at Society of Toxicology 49th Annual meeting, Salt Lake City, UT, March 07 - 11, 2010.
Impact/Purpose:
This study demonstrates that PM exposure in an aging animal model of cardiomyopathy results in cardiopulmonary injury. This model may help elucidate the mechanisms by which PM excerbates heart failure.
Description:
Human exposure to ambient PM from fossil-fuel emissions is linked to cardiovascular disease and death. This association strengthens in people with preexisting cardiac disease-especially heart failure (HF). The mechanisms explaining PM-induced exacerbation ofHF are unclear. Some ofthe effects of PM have been attributed to transition metal components. Residual oil fly ash (ROFA), a waste product of fossil fuel combustion from boilers, is rich in the transition metals Fe, Ni, and V, and when released as a fugitive particle, is an important contributor to ambient fine particulate air pollution. We hypothesized that ROFA exposure would exacerbate cardiomyopathy in the Spontaneously Hypertensive Heart Failure (SHHF) rat. At 12 months of age, SHHF rats were exposed by a single intratracheal (IT) instillation to either saline or 1.0 mg/kg ROFA (Florida Power & Light; 2.091lm diameter). Rats (n=4-5/group) were measured for carotid and left ventricular pressure (LVP) 24-hours post-IT. Electrocardiographic (ECG) and plethysmographic data were collected from a separate cohort of rats (n=4/group) before, during, and after a brief treadmill challenge 24-hours post-IT. Tissues were collected 30-min thereafter. ROFA-exposed rats had arterial hypertension, hyperglycemia, and hypercholesterolemia (increased LDL), as well as increased pulmonary macrophages, albumin, protein, and lactate dehydrogenase, indicating cardiopulmonary toxicity.-ROFA exposure significantly increased pulmonary gamrnaglutamyrtransferase, glutathione peroxidase, superoxide dismutase, and manganesesuperoxide dismutase while eliciting a trend toward increased plasma B-type natriuretic peptide, pulmonary neutrophils, and pulmonary lymphocytes. These changes indicate that ROFA elicited metabolic dysregulation concomitant with pulmonary inflammation and injury, an anti-oxidant response, and potential exacerbation of heart failure in the aged SHHF. Thus, acute PM exposure caused significant cardiopulmonary injury in aged SHHF rats, and this model may help elucidate the physiologic mechanisms by which PM exacerbates HF. ECG, LVP, and plethysmography data are currently being evaluated for post-IT changes in cardiac arrhythmias, ECG morphology, cardiac hemodynamics, and ventilatory function. (Abstract does not reflect EPA policy; Supported by UNCIEPA CR83323601.)