(2017). Carotid body resection for sympathetic modulation in systolic heart failure -results from first-in-man study. ABSTRACT AimsAugmented reflex responses from peripheral chemoreceptors, which are mainly localized in the carotid bodies (CB), characterize patients with systolic heart failure (HF) and contribute to adrenergic hyperactivation. We investigated whether surgical resection of CB in these patients can be performed safely to decrease sympathetic tone. Methods and resultsWe studied 10 male patients with systolic HF (age: 59±3 years, left ventricular ejection fraction: 27±7%) who underwent unilateral right-sided CB resection (4 patients) or bilateral CB resection (6 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 1-month visit, CB resection was associated with a significant decrease in both 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. ConclusionWe present first-in-man evidence that CB resection in patients with systolic HF is associated with decrease in sympathetic activity. 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.

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New Findings r 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. r 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 553 Response to hypoxia after carotid body removal 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.

Stimulation of peripheral chemoreceptors by acute hypoxia causes an increase in minute ventilation (VI), heart rate (HR) and arterial blood pressure (BP). However, the contribution of particular chemosensory areas, such as carotid (CB) vs. aortic bodies, to this response in humans remains unknown. We performed a blinded, randomized and placebo-controlled study in 11 conscious patients (nine men, two women) undergoing common carotid artery angiography. Doses of adenosine ranging from 4 to 512 μg or placebo solution of a matching volume were administered in randomized order via a diagnostic catheter located in a common carotid artery. Separately, ventilatory and haemodynamic responses to systemic hypoxia were also assessed. Direct excitation of a CB with intra-arterial adenosine increased VI, systolic BP, mean BP and decreased HR. No responses in these variables were seen after injections of placebo. The magnitude of the ventilatory and haemodynamic responses depended on both the dose of adenosine used and on the level of chemosensitivity as determined by the ventilatory response to hypoxia. Percutaneous radiofrequency ablation of the CB abolished the adenosine evoked respiratory response and partially depressed the cardiovascular response in one participant. The results of the present study confirm the excitatory role of purines in CB physiology in humans and suggest that adenosine may be used for selective stimulation and assessment of CB activity. The trial is registered at ClinicalTrials.gov NCT01939912.