Particulate matter induces cardiac arrhythmias via dysregulation of carotid body sensitivity and cardiac sodium channels Article

Wang, T, Lang, GD, Moreno-Vinasco, L et al. (2012). Particulate matter induces cardiac arrhythmias via dysregulation of carotid body sensitivity and cardiac sodium channels . AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY, 46(4), 524-531. 10.1165/rcmb.2011-0213OC

cited authors

  • Wang, T; Lang, GD; Moreno-Vinasco, L; Huang, Y; Goonewardena, SN; Peng, YJ; Svensson, EC; Natarajan, V; Lang, RM; Linares, JD; Breysse, PN; Geyh, AS; Samet, JM; Lussier, YA; Dudley, S; Prabhakar, NR; Garcia, JGN



  • 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 (CREB A133) exhibiting severe dilated cardiomyopathic changes were exposed to ambient PM collected in Baltimore. CREB A133 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 CREB A133 mice, and denervation of the carotid bodies significantly reduced PM-mediated cardiac arrhythmias. Genome-wide expression analyses of CREB A133 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 α-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. Copyright © 2012 by the American Thoracic Society.

publication date

  • April 1, 2012

Digital Object Identifier (DOI)

start page

  • 524

end page

  • 531


  • 46


  • 4