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Diesel exhaust worsens cardiac conduction instability in dobutamine-challenged Wistar-Kyoto and spontaneously hypertensive rats
Hazari, M., J. Lancaster, J. Starobin, A. Farraj, AND W. Cascio. Diesel exhaust worsens cardiac conduction instability in dobutamine-challenged Wistar-Kyoto and spontaneously hypertensive rats. Cardiovascular Toxicology. Humana Press Incorporated, Totowa, NJ, 17(2):120-129, (2017).
This study shows that a single exposure to diesel exhaust causes conduction instability in rats that is worse in the presence of hypertension. The RoR assessment is shown to be a valuable tool that can be used to reveal the deleterious effects of air pollution, particularly in the absence of overt symptoms. Background - Short-term exposure to air pollution, particularly from vehicular sources, increases the risk of acute cardiovascular events. However, cardiotoxicity is not always clearly discernible under ambient conditions; therefore, more subtle measures of cardiac dysfunction are necessary to elucidate the latent effects of exposure.Objective -Determine the effect of whole diesel exhaust (DE) exposure on reserve of refractoriness (RoR), an intrinsic electrophysiological measure of the heart's minimum level of refractoriness relative to development of electrical conduction instability, in rats undergoing exercise-like stress. Methods - Wistar-Kyoto (WKY) and spontaneously hypertensive (SH) rats implanted with radiotelemeters to continuously collect electrocardiogram (ECG) and heart rate (HR) were exposed to 150 ug/m3 of DE and challenged with dobutamine twenty-four hours later to mimic exercise-induced increases of the heart rate. The Chernyak-Starobin-Cohen (CSC) model was then applied to the ECG-derived QT and RR intervals collected during progressive increases in heart rate to calculate RoR for each rat. Results -Filtered air (FA)-exposed WKY and SH rats did not have any decrease in RoR, which indicates increased risk of cardiac conduction instability; however, DE caused a significant decrease in both strains. Yet, the decrease in RoR in SH rats was eight times steeper when compared to WKY rats indicating greater cardiac conduction instability in the hypertensive strain. Conclusion -These data indicate that after exposure to DE, risk of cardiac instability increases during increasing stress, particularly in the presence of underlying cardiovascular disease. Furthermore, the CSC model, which was previously shown to reveal cardiac risk in humans, can be applied to rodent toxicology studies.
This manuscript describes a new mathematical approach to assessing the adverse cardiac effects of air pollution in rodents. It is particularly novel because it reveals cardiac electrical dysfunction that is latent and will aid in future risk assessments.
Record Details:Record Type: DOCUMENT (JOURNAL/PEER REVIEWED JOURNAL)
Organization:U.S. ENVIRONMENTAL PROTECTION AGENCY
OFFICE OF RESEARCH AND DEVELOPMENT
NATIONAL HEALTH AND ENVIRONMENTAL EFFECTS RESEARCH LABORATORY
ENVIRONMENTAL PUBLIC HEALTH DIVISION
CARDIOPULMONARY AND IMMUNOTOXICOLOGY BRANCH