Diesel Exhaust Worsens Cardiac Conduction Instability in Dobutamine-Challenged Wistar–Kyoto and Spontaneously Hypertensive Rats

Abstract

Short-term exposure to air pollution, particularly from vehicular sources, increases the risk of acute clinical 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. 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. Wistar-Kyoto (WKY) and spontaneously hypertensive (SH) rats implanted with radiotelemeters to continuously collect electrocardiogram (ECG) and heart rate were exposed to 150 µg/m of DE and challenged with dobutamine 24 h 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. Filtered air-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. 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.

Non-invasive evaluation of cardiac repolarization in mice exposed to single-wall carbon nanotubes and ceria nanoparticles via intratracheal instillation

“…Specifically, spontaneously hypertensive rats exposed to diesel exhaust show a more severe drop in RoR with increasing dobutamine dosages compared to otherwise healthy animals. 7 Consequently, one direction for future research currently being explored is to consider several classes of mice with varying states of predisposition to diseases. By exposing these different groups to a variety of nanoparticles and subjecting them to dobutamine stress tests, the role of pre-existing conditions during exposure may be investigated.…”

“…Previously, the RoR has been applied to ECG measurements collected from humans 5 and rats with and without spontaneous hypertensivity. 7 In this study, we will focus our attention on otherwise healthy mice exposed to carbon nanotubes and ceria nanoparticles.…”

Early Proteome Shift and Serum Bioactivity Precede Diesel Exhaust-induced Impairment of Cardiovascular Recovery in Spontaneously Hypertensive Rats

“…We have previously shown the Spontaneously Hypertensive Rat (SHR) model to be more sensitive to diesel exhaust (DE) exposure than their normotensive counterparts 13,14 . We designed our current study to include two primary cohorts of SHRs (Fig.…”

“…The purpose of this study was to determine if serum bioactivity, alterations in the circulating milieu, and cardiovascular dysfunction all take place in Spontaneously Hypertensive Rats (SHRs) after exposure to the same air pollution source. SHRs, which we have previously determined to be more sensitive to diesel exhaust (DE) exposure than their normotensive counterparts 13,14 , have well-documented high mean arterial pressure and left ventricular hypertrophy 15 . We hypothesized that exposure-induced impairment in cardiovascular function will be preceded by an altered circulating milieu that is bioactive in vitro .…”

Measuring the time-dependent effects of dobutamine on the modulations of cardiac activity in rats

“…This criterion led to 41 trials for all SHR rats and 52 trials for all WKY rats. For further detail on the dataset, please refer to the original studies [13,14].…”