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2632635 
Journal Article 
Abstract 
Particulate matter exacerbates cardiac arrhythmias and respiratory dysynchrony in mice with heart failure via heightened carotid body sensitivity 
Lang, GD; Moreno-Vinasco, L; Wang, T; Huang, Y; Goonewaredna, S; Peng, Y; Svensson, E; Natarajan, V; Lang, R; John, B; Linares, J; Patrick, B; Geyh, A; Lussier, Y; Prabhakar, NR; Garcia, JGN 
2010 
Yes 
American Journal of Respiratory and Critical Care Medicine
ISSN: 1073-449X
EISSN: 1535-4970 
181 
A1723 
English 
WOS:000208771000723 
is part of a larger document 3452678 Proceedings of the American Thoracic Society 2010 International Conference, May 14-19, 2010, New Orleans
The mechanistic link between exposure to airborne particulate matter (PM) pollution and increased cardiovascular morbidity/mortality observed in people with congestive heart failure (CHF) is unknown. To address this important environmental health effect, genetically-engineered mice with severe dilated cardiomyopathy (cardiac-specific, dominant-negative CREB mutant transcription factor) were exposed to intratracheal doses of ambient PM (Baltimore). Compared to wild type mice, CREBA133 mice exposed to PM reflexively exhibited heightened lung inflammatory responses to PM (BAL protein, plasma IL-6 levels) as well as increased carotid body sensitivity measured by diaphragmatic EMGs and ex vivo single fiber carotid sinus nerve activity. Heightened carotid body function produced severe autonomic morbidity manifested as reduced heart rate variability, respiratory dysynchrony and marked increases in premature ventricular contractions, non-sustained ventricular tachycardia and idioventricular rhythms. Direct carotid body assessment following PM revealed pronounced afferent nerve responses to hypoxia in CREBA133 mice and hyperoxia-induced depression of breathing. Genomic analyses demonstrated greater gene deregulation in lung tissues from CREBA133 mice compared to wild type mice with robust molecular signatures of inflammation and oxidative stress. CREBA133 mice also exhibited strong evidence of inflammation, oxidative stress and ion channel pathway gene deregulation in carotid body tissues with marked up-regulation of Na+ channels (scnn1b,scn8a) and Na+-Ca+ exchangers (slc8a1) with concomitant down-regulation of 7 K+ channels (kcnd3, kcnmb2, kcnc1, kcnd1, kcnd2), findings also observed in left ventricular tissues. These findings, highly consistent with current epidemiologic findings in susceptible PM-exposed human populations, suggest that the CHF phenotype primes the lung, carotid body and left ventricle for an exaggerated response to PM which contribute to the hyperexcitability of carotid body sensory activity and an exaggerated multi-organ pathobiology. 
American Thoracic Society 2010 International Conference 
New Orleans, LA 
May 14-19, 2010