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Diesel exhaust worsens cardiac conduction instability in dobutamine-challenged spontaneously hypertensive rats
Citation:
Hazari, M., J. Lancaster, J. Starobin, A. Farraj, AND W. Cascio. Diesel exhaust worsens cardiac conduction instability in dobutamine-challenged spontaneously hypertensive rats. Presented at Society of Toxicology, Phoeix, AZ, March 23 - 27, 2014.
Impact/Purpose:
This study describes the effects of a single exposure to diesel exhaust (DE) during dobutamine challenge test, which mimics exercise "stress" testing. The work fulfills the agency goals of determining the health effects of vehicular exhaust in susceptible populations.
Description:
This study demonstrated that diesel exhaust worsened arrhythmia and cardiac function during dobutamine (simulated exercise) challenge in normotensive and hypertensive rats. The data presented here are a mathematically-derived indicator of cardiac risk, which can be used for risk assessment purposes. Loss of cardiac refractoriness, which prevents early stimulation in the heart, increases the risk of arrhythmias. Although the heart has a large reserve of refractoriness (RoR), disease can cause impairment, particularly when under stress or toxic insult, and thus conduction instability and mechanical dysfunction. RoR is an assessment of the heart’s minimum level of refractoriness as compared with the critical level associated with conduction instability. We previously showed that diesel exhaust (DE) causes cardiac electrical disturbances in rats during exercise-like stress. To further assess the subtle impacts of DE on the intrinsic conduction properties of the heart, we used the Chernyak-Starobin-Cohen (CSC) model to calculate RoR and thereby analytically determine conduction stability during dobutamine (DOB) challenge, which mimics exercise by increasing heart rate and contractility (i.e. pacing). We hypothesized that spontaneously hypertensive (SH) rats would have a greater decrease in RoR than Wistar-Kyoto (WKY) rats during pacing, and that DE would exacerbate the response. WKY and SH rats exposed to 150μg/m3 of DE were challenged with increasing doses of DOB. The CSC model was customized for each rat; QT and RR intervals taken from the electrocardiogram after a given dose of DOB were used to determine action potential durations and diastolic intervals. These values were then analyzed with conductance parameters to determine RoR. Air-exposed WKY and SH rats did not have any decrease in RoR during pacing; however, DE caused a significant decrease during pacing in both strains. SH rats had an eight times steeper decrease in RoR when compared with WKY suggesting greater risk. These data indicate that after exposure to DE, risk of instability increases with increasing cardiac stress, particularly with underlying cardiovascular disease. (This abstract does not reflect EPA policy)