You are here:
An Autonomic Link Between Inhaled Diesel Exhaust and Impaired Cardiac Performance: Insight From Treadmill and Doubutamine Challenges in Heart Failure-Prone Rats
Carll, A., M. Hazari, C. Perez, Todd Krantz, C. King, N. Coates, W. Cascio, D. Costa, AND A. Farraj. An Autonomic Link Between Inhaled Diesel Exhaust and Impaired Cardiac Performance: Insight From Treadmill and Doubutamine Challenges in Heart Failure-Prone Rats. TOXICOLOGICAL SCIENCES. Society of Toxicology, 135(2):425-26, (2013).
Background: Short-term exposure to vehicular emissions is associated with adverse cardiac events. Diesel exhaust (DE) is an ubiquitous air pollutant believed to provoke cardiac events partly through imbalance of the sympathetic and parasympathetic branches of the autonomic nervous system (ANS). Objective: We sought to test the role of ANS imbalance in DE-induced cardiotoxicity. Methods: Young adult heart failure-prone rats underwent sympathetic or parasympathetic inhibition (atenolol or atropine, respectively) during DE exposure (500 ug/m3 PM2.5, 4 h, whole-body) and were challenged with a subsequent treadmill exercise; separate anesthetized animals were challenged with a sympathetic agonist (dobutamine) with and without vagotomy during left ventricular pressure (LVP) measurements. Heart rate (HR), HR variability (HRV), electrocardiogram, and blood pressure (BP) were also measured to determine cardiac function and autonomic balance. Results: During exposure hour 2, HR, BP, and contractility markedly increased in DE-Saline rats. Atenolol significantly inhibited this, confirming DE caused mid-exposure sympathetic dominance. DE increased body temperature regardless of pretreatment. Immediately after exercise at 4 h post-DE exposure, HRV and HR changes indicated parasympathetic dominance in all groups. Conversely, during exercise recovery at 21 h post-exposure, HRV indicated DE caused sympathetic dominance but also impaired contractility and systolic BP in saline-pretreated rats. Only atenolol inhibited all three effects. LVP at 1 d indicated DE impaired contractility and lusitropy while abolishing parasympathetic-mediated lusitropic and chronotropic responses to dobutamine. Conclusions: DE-induced autonomic dysregulation of the heart involves time-dependent oscillations between sympathetic and parasympathetic dominance, with the former mediating DE’s cardiotoxicity.
Our findings demonstrate that DE-induced cardiac dysfunction is mediated in part by autonomic imbalance. These findings highlight the utility of treadmill exercise tests and dobutamine infusion as tools to unmask latents effects of air pollution exposure and imply that evidence toward the putative mechanism of autonomic-mediated air pollution cardiotoxicity may elude conventional measures due to their dependency upon uniform physiological conditions or autonomic stimuli. Additionally, our study indicates that a commonly-prescribed drug (β-adrenergic blockers) can prevent DE-induced sympatho-excitation and LV dysfunction, perhaps by inhibiting a deterioration of parasympathetic function. Ultimately, these findings strengthen eptidemiological findings by demonstrating biological plausibility, which may in turn reduce uncertainty in standard setting.
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 LAB
ENVIRONMENTAL PUBLIC HEALTH DIVISION
CARDIOPULMONARY AND IMMUNOTOXICOLOGY BRANCH