Particulate Matter Induces Cardiac Arrhythmias via Dysregulation of Carotid Body Sensitivity and Cardiac Sodium Channels

Details

• Personal Author:
  Breysse PN ; Dudley S ; Garcia JGN ; Geyh AS ; Goonewardena SN ; Huang Y ; Lang GD ; Lang RM ; Linares JD ; Lussier YA ; Moreno-Vinasco L ; Natarajan V ; Peng Y-J ; Prabhakar NR ; Samet JM ; Svensson EC ; Wang T
• Description:
  The mechanistic links between exposure to airborne particulate matter (PM) pollution and the associated increases in cardiovascular morbidity and mortality, particularly in people with congestive heart failure (CHF), have not been identified. To advance understanding of this issue, genetically engineered mice (CREBA133) exhibiting severe dilated cardiomyopathic changes were exposed to ambient PM collected in Baltimore. CREBA133 mice, which display aberrant cardiac physiology and anatomy reminiscent of human CHF, displayed evidence of basal autonomic aberrancies (compared with wild-type mice) with PM exposure via aspiration, producing significantly reduced heart rate variability, respiratory dysynchrony, and increased ventricular arrhythmias. Carotid body afferent nerve responses to hypoxia and hyperoxia-induced respiratory depression were pronounced in PM-challenged CREBA133 mice, and denervation of the carotid bodies significantly reduced PM-mediated cardiac arrhythmias. Genome-wide expression analyses of CREBA133 left ventricular tissues demonstrated prominent Na+ and K+ channel pathway gene dysregulation. Subsequent PM challenge increased tyrosine phosphorylation and nitration of the voltage-gated type V cardiac muscle a-subunit of the Na+ channel encoded by SCN5A. Ranolazine, a Na+ channel modulator that reduces late cardiac Na+ channel currents, attenuated PM-mediated cardiac arrhythmias and shortened PM-elongated QT intervals in vivo. These observations provide mechanistic insights into the epidemiologic findings in susceptibility of human CHF populations to PM exposure. Our results suggest a multiorgan pathobiology inherent to the CHF phenotype that is exaggerated by PM exposure via heightened carotid body sensitivity and cardiac Na+ channel dysfunction. [Description provided by NIOSH]
• Subjects:
  Air Pollutants, Occupational Animals Cardiovascular Diseases Cardiovascular System Occupational Health Particulate Matter Safety
• Keywords:
  Airborne Particles Animal Studies Author Keywords: Particulate Matter Cardiac Function Cardiovascular Disease Congestive Heart Failure Electromyograms Gene Expression Genotoxic Effects Heart Rate Heart Rate Variability Particulates Ventricular Arrhythmia Score

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• ISSN:
  1044-1549
• Document Type:
  Text
• Funding:
  Grant
• Genre:
  Journal Article
• Place as Subject:
  California ; Illinois ; Maryland ; OSHA Region 3 ; OSHA Region 5 ; OSHA Region 9
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Volume:
  46
• Issue:
  4
• NIOSHTIC Number:
  nn:20062676
• Citation:
  Am J Respir Cell Mol Biol 2012 Apr; 46(4):524-531
• Contact Point Address:
  Joe G. N. Garcia, M.D., Earl M. Bane Professor of Medicine, University of Illinois at Chicago, 1737 W Polk Street (MC 672), Chicago IL 60612
• Email:
  jggarcia@uic.edu
• Federal Fiscal Year:
  2012
• Performing Organization:
  Johns Hopkins University
• Peer Reviewed:
  True
• Start Date:
  20050701
• Source Full Name:
  American Journal of Respiratory Cell and Molecular Biology
• End Date:
  20280630
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:468a7aabb2aae5d97cc39cd20b278a5211020863094fd88ea8c941ddc0bada5e07e55319d55f33cdb91b061d6a8e83bcf3e84d743eeb6ae59a60913c82a0b33f
• Download URL:
  https://stacks.cdc.gov/view/cdc/225874/cdc_225874_DS1.pdf
• File Type:
  [PDF - 1.21 MB ]