You are here:
Particulate inhalation in rats causes concentration-dependent electrocardiographic, autonomic, and cardiac microRNA expression changes
Citation:
FARRAJ, A., M. S. HAZARI, N. HAYKAL-COATES, C. LAMB, D. W. WINSETT, Y. Ge, A. D. LEDBETTER, A. P. Carll, M. Bruno, AND D. L. COSTA. Particulate inhalation in rats causes concentration-dependent electrocardiographic, autonomic, and cardiac microRNA expression changes. Presented at Society of Toxicology 49th Annual meeting, Salt Lake City, UT, March 07 - 11, 2010.
Impact/Purpose:
This study demonstrates that PM inhalation elicits concentration-dependent cardiopulmonary toxicity that is likely triggered by the activation of multiple mechanisms. The propensity for one particular mechanism may be dependent on concentration.
Description:
Recently, investigators in key epidemiologic studies have demonstrated associations between fine particulate matter (PM)-associated metals and increased hospital admissions (Ni and V; Bell et al. 2009) and cardiovascular mortality (Ni and Fe; Ostro et a1. 2007). Residual oil fly ash (ROFA). a waste product of fossil fuel combustion from boilers. is rich in the transition metals Ni, V. and Fe. and when released as a fugitive particle. is ail important contributor to ambient fine PM. We hypothesized that a single inhalation exposure to transition metal-rich PM will cause concentration-dependent cardiopulmonary toxicity in Spontaneously Hypertensive (SH) rats. Rats were exposed once by nose-only inhalation for 4 hours to 3.5 mg/m3, 1.0 mg/m3 or 0.45 mg/m3 of a synthetic PM (dried salt solution) consisting of Fe. Ni and V sulfates that is similar in composition to a well-studied ROFA sample. Twenty-four hours after exposure. the high concentration of PM altered several electrocardiographic parameters including decreased T-wave amplitude and area. ST segment depression. reduced HR. and increased non-conducted P-wave arrhythmias. These changes were accompanied by pronounced pulmonary inflammation and hyper-responsivenss, decreased low frequency/high frequency ratio (LF/HF. a marker of heart rate variability (HRV)). and down-regulation of the expression of 24microRNAs (miRNA) in the myocardium. The low and middle concentrations decreased HR, but had no effects on the ST segment. arrhythmias. pulmonary inflammation or hyper-responsiveness, and affected expression of fewer miRNAs. The low concentration, however. increased T-wave amplitude and area while the middle concentration increased QRS area. Taken together, the data suggest that suggest that PM exposure triggers multiple. overlapping. mechanisms that mediate adverse cardiac effects and the extent with which a single mechanism predominates may depend on PM concentration (This abstract does not reflect EPA policy