Carotid body denervation improves autonomic and cardiac function and attenuates disordered breathing in congestive 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 (VE) 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 and VE 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 rate variability index, coefficient of variation of tidal volume and apnoea-hypopnoea index were increased in CHF-sham animals and reduced in CHF-CBD animals (P < 0.05). SRC (peak coherence) was increased in CHF-sham animals (sham-sham 0.49 ± 0.05; CHF-sham 0.79 ± 0.06), and was attenuated in CHF-CBD animals (0.59 ± 0.05) (P < 0.05 for all comparisons). Arrhythmia incidence was increased in CHF-sham and reduced in CHF-CBD animals (213 ± 58 events h(-1) CHF, 108 ± 48 events h(-1) CHF-CBD, P < 0.05). Furthermore, ventricular systolic (3.8 ± 0.7 vs. 6.3 ± 0.5 ml, P < 0.05) and diastolic (6.3 ± 1.0 vs. 9.1 ± 0.5 ml, P < 0.05) volumes were reduced, and ejection fraction preserved (41 ± 5% vs. 54 ± 2% reduction from pre-pace, P < 0.05) in CHF-CBD compared to CHF-sham rabbits. Similar patterns of changes were observed longitudinally within the CHF-CBD group before and after CBD. In conclusion, CBD is effective in reducing RSNA, SRC and arrhythmia incidence, while improving breathing stability and cardiac function in pacing-induced CHF rabbits.

Figure 1

Effect of CBD on RSNA and responses to hypoxia

Figure 2

Effect of CBD on resting RSNA in CHF

Figure 3

Effect of CBD on breathing patterns in CHF

Figure 4

Effect of CBD on oscillations in respiration and RSNA Representative recordings of V_t, RSNA and iSNA in sham–sham, CHF–sham and CHF–CBD animals. Qualitatively these tracings illustrate the concomitant oscillations in respiration and RSNA that occur in CHF, and the effect of CBD to normalize these oscillations. CBD, denervation of the carotid body; CHF, congestive heart failure; iSNA, integrated renal sympathetic nerve activity; RSNA, renal sympathetic nerve activity.

Figure 5

Effect of CBD on sympatho-respiratory coupling in CHF

Figure 6

Effect of CBD on arrhythmia incidence in CHF

Figure 7

Effect of CBD on left ventricular volumes and ejection fraction