Effects of selective carotid body stimulation with adenosine in conscious humans

KEY POINTS: In humans, excitation of peripheral chemoreceptors with systemic hypoxia causes hyperventilation, hypertension and tachycardia. However, the contribution of particular chemosensory areas (carotid vs. aortic bodies) to this response is unclear. We showed that selective stimulation of the carotid body by the injection of adenosine into the carotid artery causes a dose‐dependent increase in minute ventilation and blood pressure with a concomitant decrease in heart rate in conscious humans. The ventilatory response was abolished and the haemodynamic response was diminished following carotid body ablation. We found that the magnitude of adenosine evoked responses in minute ventilation and blood pressure was analogous to the responses evoked by hypoxia. By contrast, opposing heart rate responses were evoked by adenosine (bradycardia) vs. hypoxia (tachycardia). Intra‐carotid adenosine administration may provide a novel method for perioperative assessment of the effectiveness of carotid body ablation, which has been recently proposed as a treatment strategy for sympathetically‐mediated diseases. ABSTRACT: 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

Unilateral Carotid Body Resection in Resistant Hypertension:A Safety and Feasibility Trial

SummaryAnimal and human data indicate pathological afferent signaling emanating from the carotid body that drives sympathetically mediated elevations in blood pressure in conditions of hypertension. This first-in-man, proof-of-principle study tested the safety and feasibility of unilateral carotid body resection in 15 patients with drug-resistant hypertension. The procedure proved to be safe and feasible. Overall, no change in blood pressure was found. However, 8 patients showed significant reductions in ambulatory blood pressure coinciding with decreases in sympathetic activity. The carotid body may be a novel target for treating an identifiable subpopulation of humans with hypertension

Early Hemodynamic Changes following Surgical Ablation of the Right Greater Splanchnic Nerve for the Treatment of Heart Failure with Preserved Ejection Fraction

Background: Permanent ablation of the right greater splanchnic nerve (GSN) has previously been demonstrated to improve quality of life and functional outcomes, as well as reduce abnormally high intracardiac filling pressures, in patients with heart failure with preserved ejection fraction (HFpEF) at 1, 3 and 12 months following the procedure. We hypothesize that hemodynamic changes that ensue from surgical right GSN ablation would be apparent as early as 24 h after the medical intervention. Methods and Results: This is a prespecified analysis of a single-arm, two-center, open-label study evaluating the effects of right GSN ablation via thoracoscopic surgery in HFpEF patients with pulmonary capillary wedge pressure (PCWP) ≥15 mmHg at rest or ≥25 mmHg with supine cycle ergometry. A total of seven patients (median age 67 years, 29% female) underwent GSN removal followed by invasive right heart catheterization within 24 h. GSN ablation resulted in a significant reduction in PCWP 24 h after the procedure compared to baseline for both 20 W exercise (baseline (28.0 ± 4.3 mmHg) to 24 h (19.6 ± 6.9 mmHg); p = 0.0124) and peak exercise (baseline (25.6 ± 2.4 mmHg) to 24 h (17.4 ± 5.9 mmHg); p = 0.0025). There were no significant changes in resting or leg-up hemodynamics. Conclusions: Permanent right GSN ablation leads to a reduction in intracardiac filling pressures during exercise, apparent as early as 24 h following the procedure

Hypertension is critically dependent on the carotid body input in the spontaneously hypertensive rat

The peripheral chemoreflex is known to be enhanced in individuals with hypertension. In pre-hypertensive (PH) and adult spontaneously hypertensive rats (SHRs) carotid body type I (glomus) cells exhibit hypersensitivity to chemosensory stimuli and elevated sympathoexcitatory responses to peripheral chemoreceptor stimulation. Herein, we eliminated carotid body inputs in both PH-SHRs and SHRs to test the hypothesis that heightened peripheral chemoreceptor activity contributes to both the development and maintenance of hypertension. The carotid sinus nerves were surgically denervated under general anaesthesia in 4- and 12-week-old SHRs. Control groups comprised sham-operated SHRs and aged-matched sham-operated and carotid sinus nerve denervated Wistar rats. Arterial blood pressure was recorded chronically in conscious, freely moving animals. Successful carotid sinus nerve denervation (CSD) was confirmed by testing respiratory responses to hypoxia (10% O(2)) or cardiovascular responses to i.v. injection of sodium cyanide. In the SHR, CSD reduced both the development of hypertension and its maintenance (P < 0.05) and was associated with a reduction in sympathetic vasomotor tone (as revealed by frequency domain analysis and reduced arterial pressure responses to administration of hexamethonium; P < 0.05 vs. sham-operated SHR) and an improvement in baroreflex sensitivity. No effect on blood pressure was observed in sham-operated SHRs or Wistar rats. In conclusion, carotid sinus nerve inputs from the carotid body are, in part, responsible for elevated sympathetic tone and critical for the genesis of hypertension in the developing SHR and its maintenance in later life

Hypertension is critically dependent on the carotid body input in the spontaneously hypertensive rat

The peripheral chemoreflex is known to be enhanced in individuals with hypertension. In pre-hypertensive (PH) and adult spontaneously hypertensive rats (SHRs) carotid body type I (glomus) cells exhibit hypersensitivity to chemosensory stimuli and elevated sympathoexcitatory responses to peripheral chemoreceptor stimulation. Herein, we eliminated carotid body inputs in both PH-SHRs and SHRs to test the hypothesis that heightened peripheral chemoreceptor activity contributes to both the development and maintenance of hypertension. The carotid sinus nerves were surgically denervated under general anaesthesia in 4- and 12-week-old SHRs. Control groups comprised sham-operated SHRs and aged-matched sham-operated and carotid sinus nerve denervated Wistar rats. Arterial blood pressure was recorded chronically in conscious, freely moving animals. Successful carotid sinus nerve denervation (CSD) was confirmed by testing respiratory responses to hypoxia (10% O(2)) or cardiovascular responses to i.v. injection of sodium cyanide. In the SHR, CSD reduced both the development of hypertension and its maintenance (P < 0.05) and was associated with a reduction in sympathetic vasomotor tone (as revealed by frequency domain analysis and reduced arterial pressure responses to administration of hexamethonium; P < 0.05 vs. sham-operated SHR) and an improvement in baroreflex sensitivity. No effect on blood pressure was observed in sham-operated SHRs or Wistar rats. In conclusion, carotid sinus nerve inputs from the carotid body are, in part, responsible for elevated sympathetic tone and critical for the genesis of hypertension in the developing SHR and its maintenance in later life