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Respiratory Rate Response to Hypercapnic and Hypoxic Stimuli in Mice via the Carotid Body Is Attenuated by IL6-Induced by Resistive Breathing but not by TNFa FREE TO VIEW

Fotis Perlikos, MD; Ioannis Koutsourelakis; Maria Detoraki; Adamandia Sotiriou; Haroula-Eleni Giannakopoulou; Apostolos Papalois; Theodoros Vassilakopoulos
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Evangelismos General Hospital, Athens, Greece

Copyright 2016, American College of Chest Physicians. All Rights Reserved.

Chest. 2016;150(4_S):840A. doi:10.1016/j.chest.2016.08.940
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SESSION TYPE: Original Investigation Poster

PRESENTED ON: Wednesday, October 26, 2016 at 01:30 PM - 02:30 PM

PURPOSE: The carotid body is one of the three main contributing afferent neural pathways to the control of breathing. Our aim is to investigate the role of cytokines IL-6 and TNFa, induced by resistive breathing, on the respiratory rate responce, via the carotid body.

METHODS: 16 IL-6 deficient mice (IL-6-/-) and 16 TNFa deficient mice (TNFa-/-) where used, together with 16 appropriate wild type (WT) controls (C57/BL6), all males 8 to 10 weeks old, divided in two groups each (n=8). All mice were subjected to whole body plethysmography (WBP) during exposure to the following mixtures: 21%O2-79%N2, 100%O2, 7%CO2-21%O2-72%N2, 7%CO2-10%O2-83%N2 and 10%O2-90%N2. After 24 hours half of each of the three types of mice underwent Carotid Body Deafferentiation (CBD) which is bilateral dissection of the carotid sinus nerve and the other half sham operation. After 48 hours all mice underwent tracheal banding (TB) to reduce trachea surface by 50% and induce resistive breathing. A final WBP followed after 24 hours.

RESULTS: The wild type mice that underwent CBD and TB showed reduction of Respiratory Rate (RR), compared to before the operations, of 59,1% and 48,4% for gas mixtures 7%CO2-21%O2-72%N2 and 10%O2-90%N2 respectively, which are statistically significantly lower compared to the reduction showed by wild type mice that underwent sham operation and TB. This effect was reproduced in TNFa-/- mice but not IL-6-/- mice. No statistically significant difference in RR was found between the reduction in TNFa-/- mice and wild type. In IL-6-/- mice there was a statistically significantly smaller, compared to wild type mice, reduction in RR of 27,2%, 29,2% and 15,4%, for gas mixtures 7%CO2-21%O2-72%N2, 7%CO2-10%O2-83%N2 and 10%O2-90%N2 respectively.

CONCLUSIONS: Induced by resistive breathing, due to tracheal banding, IL-6 but not TNFa downregulates the respiratory controller response for RR via the carotid body.

CLINICAL IMPLICATIONS: This study offers a better understanding of the underlying pathophysiologic mechanisms that affect the ventilatory control during strenuous resistive breathing, like is seen in COPD or Asthma exacerbations.

DISCLOSURE: The following authors have nothing to disclose: Fotis Perlikos, Ioannis Koutsourelakis, Maria Detoraki, Adamandia Sotiriou, Haroula-Eleni Giannakopoulou, Apostolos Papalois, Theodoros Vassilakopoulos

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