Abstract

Enhanced carotid body (CB) chemoreflex sensitivity in systolic heart failure (HF) has been linked to oscillatory breathing patterns and autonomic imbalance. Importantly, breathing pattern alterations and heightened chemoreflex‐mediated sympathetic nerve activity are both associated with higher morbidity and mortality in HF. Therefore, the objective of this study was to determine whether CB denervation (CBD) would improve respiratory stability and decrease sympathetic drive in HF. In rabbits with pacing‐induced HF, we measured resting breathing and renal sympathetic nerve activity (RSNA), before and after CBD. In addition, we assessed respiratory‐sympathetic coupling using power spectral analysis and the magnitude of the peak coherence function between tidal volume (Vt) and RSNA frequency spectra. Minute ventilation and RSNA responses to acute hypoxia were significantly augmented in HF compared to controls and were abolished by CBD. Resting RSNA was greater in HF compared to control animals (43 ± 5% max vs. 23 ± % max, p<0.05). HF animals after CBD displayed resting RSNA levels similar to control animals. HF animals displayed altered breathing patterns characterized by oscillatory breathing and increases in the incidence of apneas/hypopneas. Remarkably, CBD totally normalized oscillatory breathing patterns in HF animals. Peak coherence between RSNA and Vt signals was increased in HF animals (control 0.49 ± 0.05; HF 0.79 ± 0.06), and was significantly attenuated by CBD (0.59 ± 0.05, p<0.05 for all comparisons). Our data show that enhanced CB‐mediated chemoreflex drive contributes to tonic elevations in RSNA and breathing instability in HF. Additionally, a tonic increase in CB afferent discharge may also play an important role in strengthening a link between respiratory and sympathetic neural outflow in HF.Support or Funding InformationSupported by Fondecyt 1140275, NIH PO1‐HL62222 and NIH F32 HL108592‐01A1.

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