You are here:
Aconitine "challenge" test reveals a single whole-body exposure to diesel exhaust increases cardiac arrhythmia risk in hypertensive rats
Citation:
HAZARI, M. S., C. LAMB, AND A. P. Carll. Aconitine "challenge" test reveals a single whole-body exposure to diesel exhaust increases cardiac arrhythmia risk in hypertensive rats. Presented at American Associaton for Aerosol Research (AAAR), San Diego, CA, March 22 - 26, 2010.
Impact/Purpose:
In this study, we employed the aconitine challenge test to examine whether a single inhalation exposure to diesel exhaust (DE) would increase the risk of arrhythmia being triggered in a rat model of hypertension.
Description:
Epidemiological studies demonstrate a significant association between cardiac electrical dysfunction, arrhythmias and air pollution exposure. Sensitivity to aconitine-induced arrhythmia has been used repeatedly to examine the factors that increase the risk of such cardiac electrical dysfunction. Using this technique, we previously demonstrated that a single exposure to particulate matter (PM) or acrolein gas increased the risk of developing arrhythmia in hypertensive rats (Hazari et al. 2009). In this study, we employed the aconitine challenge test to examine whether a single inhalation exposure to diesel exhaust (DE) would increase the risk of arrhythmia being triggered in a rat model of hypertension. We hypothesized that: (1) exposure to whole DE would increase the risk of aconitine-induced arrhythmia, and (2) exposure to filtered, particulate-free DE would alter responsiveness to the challenge. Spontaneously hypertensive (SH) rats surgically implanted with radiotelemeters were exposed whole-body to 500 ug/m3 of whole DE, 500 ug/m3 of DE filtered to remove PM or filtered air for 6 hours. Arrhythmogenesis was assessed 24 hours later in urethane-anesthetized animals by continuous intravenous infusion of aconitine while heart rate (HR), electrocardiogram (ECG) and ventilatory parameters were monitored. Rats exposed to either whole or filtered DE had lower HR when compared to air-exposed animals. Exposure to either whole or filtered DE resulted in significantly shorter PR intervals, and significantly prolonged QRS complex duration, corrected QT (QTc), and corrected IT (JTc) in the ECG when compared to air controls. Interestingly, overall heart rate variability (HRV) was significantly increased in rats exposed to either whole or filtered DE; however only rats exposed to filtered DE had a significant increase in Lf/Hf; or increase in sympathetic modulation. Sensitivity to arrhythmia was measured as the threshold dose of aconitine required to produce ventricular premature beats (VPB), ventricular tachycardia (VT), and ventricular fibrillation (VF). Rats exposed to air developed VPB's, VT, and VF successively during aconitine infusion. Rats exposed to whole DE developed VPB's, VT, and VF at lower doses of aconitine than air-exposed animals, and the cumulative dose of aconitine required to elicit these responses was even lower in animals exposed to filtered DE. These findings suggest that a single exposure to DE increases the sensitivity of the cardiac electrical conduction system and may increase the risk of triggered arrhythmias. Additionally, the findings that filtered DE (i.e., gases alone) elicits more cardiotoxic effects at these exposure levels than whole DE suggest that delineating the effects of complex air multipollutants at a specific air shed and their individual components needs to be further studied. Thus, this form ofphysiological "challenge" testing may be a reasonable approach to clarify the component effects of air pollution. (This abstract does not reflect EPA policy.)