Effect of Carotid Body Denervation (CBD) on Breathing and Central Neuromodulation

Abstract

After CBD, goats hypoventilate and exhibit reduced CO2 sensitivity followed by a partial recovery in the weeks following (Pan et al, 1998). Currently, the contribution of central mechanisms in these changes is unknown; however, perturbations involving the carotid bodies have been show to affect central neuromodulator/neurotransmitter (NM/NT) levels within the respiratory network (Goiny et al, 1991; Hoop at al, 1999). Here, we tested the hypothesis that the time‐dependent changes in breathing following CBD are associated with altered central NM/NT levels within the pre‐Bötzinger Complex (pre‐BötC). In 6 awake adult goats, on several days pre‐ and post‐CBD we assessed resting PaCO2, CO2 sensitivity, and the NM/NT content of mock cerebrospinal fluid (mCSF) dialyzed into the pre‐BötC. From days 0–15 post‐CBD, we observed hypoventilation and reduced CO2 sensitivity, with a concomitant increase in GABA and Glycine and a decrease in serotonin and Substance‐P in the dialyzed mCSF. From days 16–30 post‐CBD, we observed a partial recovery of resting PaCO2, but little recovery of CO2 sensitivity or NMs/NTs. In conclusion, a shift in the balance of NMs/NTs toward net inhibition at the pre‐BötC may contribute to the hypoventilation and reduced CO2 sensitivity following CBD. Supported by NIH 25739 and Veterans Association