Carotid body denervation improves autonomic and cardiac function and attenuates disordered breathing in congestive heart failure

Abstract

Key pointsr A strong correlation between disordered breathing patterns, elevated sympathetic nerve activity and enhanced chemoreflex sensitivity exists in patients with heart failure.r Evidence indicates that disordered breathing patterns and increased sympathetic nerve activity increases arrhythmia incidence in patients with heart failure.r Enhanced coupling between sympathetic and respiratory neural drive underlies elevated sympathetic nerve activity in an animal model of sleep apnoea.r We investigated the impact of carotid body chemoreceptor denervation on sympathetic nerve activity, disordered breathing and sympatho-respiratory coupling in an animal model of heart failure.r Renal sympathetic nerve activity, apnoea/hypopnoea incidence, variability measures of tidal volume and respiratory rate and arrhythmia incidence were quantified during resting breathing in heart failure animals with and without carotid body ablation.r Our results indicate that carotid body chemoreceptor denervation reduces sympathetic nerve activity, disordered breathing patterns, arrhythmia incidence and sympatho-respiratory coupling in experimental heart failure.r These findings suggest that device-oriented ablation of carotid body chemoreceptors is a viable treatment option for reduction of sympathetic nerve activity, disordered breathing patterns and arrhythmia incidence in heart failure.Abstract In congestive heart failure (CHF), carotid body (CB) chemoreceptor activity is enhanced and is associated with oscillatory (Cheyne-Stokes) breathing patterns, increased sympathetic nerve activity (SNA) and increased arrhythmia incidence. We hypothesized that denervation of the CB (CBD) chemoreceptors would reduce SNA, reduce apnoea and arrhythmia incidence and improve ventricular function in pacing-induced CHF rabbits. Resting breathing, renal SNA (RSNA) and arrhythmia incidence were measured in three groups of animals: (1) sham CHF/sham-CBD (sham-sham); (2) CHF/sham-CBD (CHF-sham); and (3) CHF/CBD (CHF-CBD). Chemoreflex sensitivity was measured as the RSNA and minute ventilatory (V E ) responses to hypoxia and hypercapnia. Respiratory pattern was measured by plethysmography and quantified by an apnoea-hypopnoea index, respiratory rate variability index and the coefficient of variation of tidal volume. Sympatho-respiratory coupling (SRC) was assessed using power spectral analysis and the magnitude of the peak coherence function between tidal volume and RSNA frequency spectra. Arrhythmia incidence and low frequency/high frequency ratio of heart rate variability were assessed using ECG and blood pressure waveforms, respectively. RSNA andV E responses to hypoxia were augmented in CHF-sham and abolished in CHF-CBD animals. Resting RSNA was greater in CHF-sham compared to sham-sham animals (43 ± 5% max vs. 23 ± 2% max, P < 0.05), and this increase was not found in CHF-CBD animals (25 ± 1% max, P < 0.05 vs. CHF-sham). Low frequency/high frequency heart rate variability ratio was similarly increased in CHF and reduced by CBD (P < 0.05). Respiratory ...

Neural Control of Respiration by the Retrotrapezoid Nucleus.

“…The apneas have been tentatively attributed to recurrent episodes of CNS hypocarbia that silence CRCs (Dempsey et al, 2012;Marcus et al, 2014). This interpretation agrees with the finding that respiratory alkalosis silences RTN in conscious rats (Basting et al, 2015).…”

“…In CCHS patients, breathing is much better maintained during REM than non-REM sleep (Fleming et al, 1980). In short, reduced CRC activity resulting from carotid body hyperactivity (hypoxia, CHF) (Marcus et al, 2014) or RTN lesion (putative cause of CCHS) appears to cause central sleep apnea (CSA) selectively during non-REM sleep.…”

Congestive Heart Failure and Central Sleep Apnea

“…Dynamic CO 2 therapy, applied during the hyperventilation phase of CSR to prevent hypocapnia, can resolve CSR during wakefulness without considerably raising mean ventilation (131,132). Finally, denervation of the carotid-body chemoreceptors has been shown in animal studies to improve survival in CHF, and a case patient with CHF improved sleep disordered breathing, exercise capacity and quality of life (133,134).…”

Carotid Body: A New Target for Rescuing Neural Control of Cardiorespiratory Balance in Disease

“…Ribeiro et al (2013) demonstrate how CBD prevents the development of insulin resistance and hypertension induced by hypercaloric diets. The most comprehensive animal study with which we are familiar is that of Marcus and his colleagues in CHF rabbits (Marcus et al, 2014). In brief, their study showed how CBD reduced sympathetic nerve activity, disordered breathing patterns, arrhythmia incidence, and sympatho-respiratory coupling in CHF rabbits.…”