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TRPA1 and Sympathetic Activation contribute to increased risk of triggered cardiac arrhythmias in hypertensive rats exposed to diesel exhaust
Citation:
HAZARI, M. S., N. HAYKAL-COATES, D. W. WINSETT, Q. T. KRANTZ, C. KING, D. L. COSTA, AND A. FARRAJ. TRPA1 and Sympathetic Activation contribute to increased risk of triggered cardiac arrhythmias in hypertensive rats exposed to diesel exhaust. ENVIRONMENTAL HEALTH PERSPECTIVES. National Institute of Environmental Health Sciences (NIEHS), Research Triangle Park, NC, 119(7):951-7, (2011).
Impact/Purpose:
This study describes the effects of a single exposure to diesel exhaust (DE) on aconitine-induced arrhythmogenicity in spontaneously hypertensive (SH) rats. A lower cumulative dose of aconitine was needed to elicit arrhythmia in rats exposed to DE (l50ug/m3) when compared to air-exposed controls
Description:
Background -Diesel exhaust (DE), which is emitted from on-and off-road sources, is a complex mixture of toxic gaseous and particulate components that results in adverse cardiovascular effects. Arrhythmias, which are often triggered in the hours and days following exposure, are one of the main pathways leading to acute cardiac events. Objective -Our goal was to test the hypothesis that increased risk of triggered arrhythmias one day after DE exposure is mediated by TRPA1 (sensory irritation) and subsequent autonomic imbalance. Methods -Spontaneously hypertensive (SH) rats surgically implanted with radiotelemeters were exposed whole-body to either 500 ug/m3 (high) of whole (w)-DE or filtered (f)-DE, or 150ug/m3 (low) of wDE or fDE (4 hours). Arrhythmogenesis was assessed 24hrs later by continuous intravenous infusion of aconitine, an arrhythmogenic drug, while heart rate (HR) and electrocardiogram (ECG) were monitored throughout. Results -Rats exposed to DE had slightly higher HR and increased LF/HF, or increased sympathetic modulation, when compared to air controls; ECG showed prolonged ventricular depolarization and shortened repolarization periods. Rats exposed to wDE developed arrhythmia at lower doses of aconitine than controls; the dose was even lower in rats exposed to fDE. Pretreatment of low wDE-exposed rats with a TRPA1 antagonist prevented the heightened sensitivity to arrhythmia. In separate animals, only sympathetic blockade decreased sensitivity to arrhythmia post-DE. Conclusions -These findings suggest that a single exposure to DE increases the sensitivity of the heart to triggered arrhythmias. It appears the gaseous components play an important role in the pro-arrhythmic response, which may be mediated by activation of TRPA1, and subsequent sympathetic modulation. As such, toxic inhalants like DE may partly exhibit their toxicity by lowering the threshold for secondary triggers complicating assessment of their risk. (This abstract does not reflect EPA policy)
