title: Effects of selective carotid body stimulation with adenosine in conscious humans.
abstract: 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.
  
  
  
  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.
authors.affiliation: Department of Cardiology, Centre for Heart Diseases, 4th Military Hospital, Wroclaw, Poland. stanislaw.tubek@gmail.com.|Department of Heart Diseases, Faculty of Health Sciences, Wroclaw Medical University, Wroclaw, Poland. stanislaw.tubek@gmail.com.
authors.forename: Stanislaw
authors.initials: S
authors.lastname: Tubek
authors.affiliation: Department of Cardiology, Centre for Heart Diseases, 4th Military Hospital, Wroclaw, Poland.
authors.forename: Piotr
authors.initials: P
authors.lastname: Niewinski
authors.affiliation: Department of Cardiology, Centre for Heart Diseases, 4th Military Hospital, Wroclaw, Poland.|Department of Heart Diseases, Faculty of Health Sciences, Wroclaw Medical University, Wroclaw, Poland.
authors.forename: Krzysztof
authors.initials: K
authors.lastname: Reczuch
authors.affiliation: Department of Vascular Surgery, 4th Military Hospital, Wroclaw, Poland.|Department of Clinical Proceedings, Faculty of Health Sciences, Wroclaw Medical University, Wroclaw, Poland.
authors.forename: Dariusz
authors.initials: D
authors.lastname: Janczak
authors.affiliation: Department of Vascular Surgery, 4th Military Hospital, Wroclaw, Poland.
authors.forename: Artur
authors.initials: A
authors.lastname: Rucinski
authors.affiliation: Department of Physiology, Wroclaw Medical University, Wroclaw, Poland.
authors.forename: Bartlomiej
authors.initials: B
authors.lastname: Paleczny
authors.affiliation: CIBIEM Inc, Los Altos, CA, USA.
authors.forename: Zoar J
authors.initials: ZJ
authors.lastname: Engelman
authors.affiliation: Department of Cardiology, Centre for Heart Diseases, 4th Military Hospital, Wroclaw, Poland.
authors.forename: Waldemar
authors.initials: W
authors.lastname: Banasiak
authors.affiliation: School of Physiology, Pharmacology & Neuroscience, Biomedical Sciences, University of Bristol, Bristol, UK.
authors.forename: Julian F R
authors.initials: JF
authors.lastname: Paton
authors.affiliation: Department of Cardiology, Centre for Heart Diseases, 4th Military Hospital, Wroclaw, Poland.|Department of Heart Diseases, Faculty of Health Sciences, Wroclaw Medical University, Wroclaw, Poland.
authors.forename: Piotr
authors.initials: P
authors.lastname: Ponikowski
mesh_terms: D000241:Adenosine / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D000368:Aged; D017704:Baroreflex; D002344:Carotid Body / Q000187:drug effects* / Q000502:physiology; D003243:Consciousness; D005260:Female; D006439:Hemodynamics; D006801:Humans; D000860:Hypoxia / Q000188:drug therapy* / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D012123:Pulmonary Ventilation
chemical_list: D000241:Adenosine
keywords: adenosine; carotid body; chemoreflex