Citation:

Carll, A., M. Hazari, C. Perez, Todd Krantz, C. King, D. Winsett, D. Costa, AND A. Farraj. Diesel Exhaust-Induced Cardiac Dysfunction Is Mediated by Sympathetic Dominance in Heart Failure-Prone Rats. Presented at Society of Toxicology Annual meeting, March 10 - 14, 2013.

Impact/Purpose:

This study demonstrates that diesel exhaust induced cardiac dysfunction is mediated by autonomic fluctuations precipitated by early sympathetic dominance. These findings help establish biological plausibility for the epidemiological data that links exposure to air pollution to increased cardiovascular morbidity and mortality.

Description:

Short-term exposure to vehicular emissions is associated with adverse cardiac events. Diesel exhaust (DE) may provoke cardiac events through defective co-ordination of the two main autonomic nervous system (ANS) branches. We exposed heart failure-prone rats once to DE (500 g/m3 PM2.5, 4 h, whole-body inhalation) and tested for ANS-mediation of cardiotoxicity by several interventions, including post-DE sympathetic agonism (dobutamine) before and after parasympathetic ablation (vagotomy) and, separately, sympathetic or parasympathetic inhibition (atenolol or atropine) and treadmill exercise after DE exposure. Left ventricular pressure (LVP) pressure, heart rate (HR), HR variability (HRV), and blood pressure (BP) were measured to determine cardiac function and autonomic balance. During exposure hour 2, DE markedly increased HR, BP and contractility in saline-pretreated rats, and atenolol entirely inhibited these effects, indicating DE caused mid-exposure sympathetic excitation. DE increased body temperature regardless of pretreatment. Upon exercise recovery at 4 h post-exposure, HRV and HR indicated that DE increased parasympathetic influence. Conversely, during exercise recovery at 21 h post-exposure, DE increased sympathetic influence in saline-pretreated rats, while it impaired contractility and decreased systolic BP in saline- and atropine-pretreated rats. Atenolol inhibited all of these effects. LVP at 1 d post-DE indicated systolic and diastolic dysfunction and altered diastolic and chronotropic responses to dobutamine were mediated partly through sympathetic dominance. Thus, DE-induced autonomic dysregulation of the heart involves time-dependent oscillations between sympathetic and parasympathetic dominance, with the former mediating DE’s cardiotoxic effects. (Does not reflect EPA policy. Funded by EPA/UNC CR-83515201-0)

Record Details: