The Influence of Autonomic Imbalance on Diesel Exhaust-Induced Cardiac Dysfunction in Heart Failure-Prone Rats Public Deposited

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  • March 22, 2019
Creator
  • Carll, Alex Perrow
    • Affiliation: Gillings School of Global Public Health, Department of Environmental Sciences and Engineering
Abstract
  • Short-term exposure to vehicular emissions is strongly associated with adverse cardiac events. Diesel exhaust (DE) is a ubiquitous air pollutant hypothesized to provoke adverse cardiac events partly through defective co-ordination of the sympathetic and parasympathetic branches of the autonomic nervous system. To investigate this putative mechanism, cardiophysiologic responses to a single DE inhalation exposure (500 μg/m3, 4 h, whole-body) were examined in heart failure-prone rats and age-related susceptibility or autonomic challenges were incorporated to reveal latent effects. Challenges included sympathetic stimulation (dobutamine) with and without parasympathetic ablation (vagotomy) and, separately, treadmill exercise and pretreatment with a sympathetic or parasympathetic inhibitor. Measures of cardiac function by left ventricular (LV) pressure and echocardiography, autonomic balance by heart rate (HR) and HR variability (HRV), electrocardiogram, and aortic pressure were performed. DE increased cardiac output, bradyarrhythmias, and parasympathetic tone while altering ventricular repolarization in aged heart failure-prone rats during or shortly after exposure. Exercise also revealed a DE-induced increase in parasympathetic tone in young adult rats shortly after exposure. At 1 day post-exposure, dobutamine and treadmill challenges indicated that DE increased sympathetic influence, but pre-treatment with autonomic inhibitors prevented this. Only sympathetic inhibition prevented a DE-induced decline in contractility and systolic blood pressure at exercise 1 day after exposure. Vagotomy revealed that DE caused systolic and diastolic dysfunction and altered diastolic and chronotropic responses to dobutamine through impaired parasympathetic regulation. Thus, altered autonomic regulation of the heart, characterized by an early parasympathetic dominance and a delayed sympathetic dominance, mediates adverse cardiac effects of air pollution exposure. This research elucidates a major physiologic mechanism driving the adverse health effects of air pollutant exposure. Consequently, these findings will inform health risk assessments, medical therapies, and environmental controls for air pollution.
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  • In Copyright
Advisor
  • Farraj, Aimen K.
Degree
  • Doctor of Philosophy
Degree granting institution
  • University of North Carolina at Chapel Hill
Graduation year
  • 2012
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