Aims Augmented reflex responses from peripheral chemoreceptors, which are mainly localized in the carotid bodies (CBs), characterize patients with systolic heart failure and contribute to adrenergic hyperactivation. We investigated whether surgical resection of CBs in these patients can be performed safely to decrease sympathetic tone. Methods and results We studied 10 male patients with systolic heart failure (age, 59 ± 3 years; LVEF, 27 ± 7%) who underwent unilateral right‐sided CB resection (four patients) or bilateral CB resection (six patients). Primary endpoints of the study were changes in muscle sympathetic nerve activity (MSNA) and peripheral chemosensitivity measured as ventilatory response to hypoxia from baseline to 1 month post‐CB resection. Safety analysis included analysis of arterial blood gas and oxygenation at night through 2 months post‐procedure and adverse events assessed up to 12 months. At the 1‐month visit, CB resection was associated with a significant decrease both in MSNA (86.6 ± 3.1 vs. 79.7 ± 4.2 bursts/100 beats, P = 0.03) and in peripheral chemosensitivity (1.35 ± 0.19 vs. 0.41 ± 0.17 L/min/SpO₂, P = 0.005). It also resulted in improved exercise tolerance. Amongst some patients with bilateral CB resection, there was a trend towards worsening of oxygen saturation at night, which in one case required therapy with non‐invasive ventilation. Conclusion We present first‐in‐man evidence that CB resection in patients with systolic heart failure is associated with a decrease in sympathetic activity. A bilateral procedure may carry a risk of worsening oxygenation at night. CB modulation constitutes an interesting research avenue, but careful consideration of the balance between safety and efficacy is necessary before further clinical trials.

New Findings: What is the central question of this study? Carotid body denervation removes the ventilatory response to acute hypoxia, although haemodynamic responses to acute hypoxia after carotid body removal have not been described conclusively in humans. What is the main finding and its importance? Carotid body removal results in dissociation of heart rate and blood pressure responses to hypoxia in human subjects. While the heart rate response (tachycardia) is maintained, there is a significant attenuation of the blood pressure response (hypertension), which indicates the existence of different sensory afferent pathways in the haemodynamic response to hypoxia that has important clinical implications for this novel therapeutic modality. While the ventilatory response to hypoxia is known to be mediated by the carotid bodies, the origin of the haemodynamic alterations evoked by hypoxia is less certain. Bilateral carotid body removal (CBR) performed to treat congestive heart failure may serve as a model to improve our understanding of haemodynamic responses to hypoxia in humans. We studied six congestive heart failure patients before and 1 month after CBR [median (interquartile range): age, 58.5 (56–61) years old; and ejection fraction, 32 (25–34)%]. Peripheral chemosensitivity (hypoxic ventilatory response) was equated to the slope relating lowest oxygen saturation to highest minute ventilation following exposures to hypoxia. Likewise, systolic blood pressure (SBP), diastolic blood pressure (DBP) and heart rate (HR) slopes were calculated as slopes relating the lowest oxygen saturations to the highest SBP, DBP and HR responses. We found that CBR reduces the hypoxic ventilatory response (∆91%, P < 0.05), SBP (∆71%, P < 0.05) and DBP slopes (∆59%, P = 0.07). In contrast, the HR slope remained unchanged. The dissociation between the blood pressure and HR responses after CBR shows involvement of a different chemoreceptive site(s) maintaining the response to acute hypoxia. We conclude that carotid bodies are responsible for ventilatory and blood pressure responses, while the HR response might be mediated by the aortic bodies. The significant reduction of the blood pressure response to hypoxia after CBR suggests a decrease in sympathetic tone, which is of particular clinical relevance in congestive heart failure.

Key points: Low‐dose dopamine reduces the ventilatory response to acute hypoxia both in animal and in human studies. In this study we show that low‐dose dopamine also attenuates the haemodynamic responses (tachycardia, hypertension) to acute hypoxia in healthy humans. Moreover, we found that dopamine withdrawal results in a temporary increase in minute ventilation. The magnitude of the increase in minute ventilation after dopamine withdrawal correlates with the degree of ventilatory response to acute hypoxia and depends on the duration of dopamine administration. Dopamine may provide a novel method for assessing differences in the level of peripheral chemoreceptor activity, which has important clinical implications given the recently reported pathological role of the carotid body in cardiovascular diseases in animals and humans. Low‐dose dopamine inhibits peripheral chemoreceptors and attenuates the hypoxic ventilatory response (HVR) in humans. However, it is unknown: (1) whether it also modulates the haemodynamic reactions to acute hypoxia, (2) whether it also modulates cardiac baroreflex sensitivity (BRS) and (3) if there is any effect of dopamine withdrawal. We performed a double‐blind, placebo‐controlled study on 11 healthy male volunteers. At sea level over 2 days every subject was administered low‐dose dopamine (2 μg kg^–1 min^–1) or saline infusion, during which we assessed both ventilatory and haemodynamic responses to acute hypoxia. Separately, we evaluated effects of initiation and withdrawal of each infusion and BRS. The initiation of dopamine infusion did not affect minute ventilation (MV) or mean blood pressure (MAP), but increased both heart rate (HR) and cardiac output. Concomitantly, it decreased systemic vascular resistance. Dopamine blunted the ventilatory, MAP and HR reactions (hypertension, tachycardia) to acute hypoxia. Dopamine attenuated cardiac BRS to falling blood pressure. Dopamine withdrawal evoked an increase in MV. The magnitude of the increment in MV due to dopamine withdrawal correlated with the size of the HVR and depended on the duration of dopamine administration. The ventilatory reaction to dopamine withdrawal constitutes a novel index of peripheral chemoreceptor function.