Trial reportCirculation2017
Nitrite and S-Nitrosohemoglobin Exchange Across the Human Cerebral and Femoral Circulation: Relationship to Basal and Exercise Blood Flow Responses to Hypoxia.
Trial report in Circulation, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers, 2 of them syntheses that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
30 citing papers in PubMed, 2 syntheses or guidelines pooled it, 66 citations in OpenAlex.
- Predictive Value of Red Blood Cell Distribution Width for the Prognosis of Cardiac Arrest: A Systematic Review and Meta-Analysis.Reviews in cardiovascular medicine · 2025Pooled it
- Peripheral Blood and Salivary Biomarkers of Blood-Brain Barrier Permeability and Neuronal Damage: Clinical and Applied Concepts.Frontiers in neurology · 2020Pooled it
- Psychological stress catalyses free radical-mediated activation of coagulation in humans.The Journal of physiology · 2026Trial
- Acute hypoxia impairs posterior cerebral bioenergetics and memory in man.Experimental physiology · 2023Trial
- Effects of continuous hypoxia on flow-mediated dilation in the cerebral and systemic circulation: on the regulatory significance of shear rate phenotype.The journal of physiological sciences : JPS · 2022Trial
- Integrative regulation of cerebral blood flow in response to exercise and environmental extremes.Experimental physiology · 2026Article
- Linking dynamic cerebral autoregulation and inhibitory executive function: Role of modifiable behaviours.Experimental physiology · 2026Review
- Exercise-induced potentiation of the acute hypoxic ventilatory response: Neural mechanisms and implications for cerebral blood flow.Experimental physiology · 2024Review
- My sojourn with cerebral sympathetic nervous activity.Experimental physiology · 2024Article
- Supervised exercise training improves cardiorespiratory fitness and reduces perioperative risk in peripheral artery disease patients with intermittent claudication.Annals of the Royal College of Surgeons of England · 2024Article
- Professor Niels Henry Secher: Celebrating success from boat to bench to bedside.Experimental physiology · 2023Article
- Hemoglobin and cerebral hypoxic vasodilation in humans: Evidence for nitric oxide-dependent andJournal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2023Article
- Lower systemic nitric oxide bioactivity, cerebral hypoperfusion and accelerated cognitive decline in formerly concussed retired rugby union players.Experimental physiology · 2023Article
- Lifelong exposure to high-altitude hypoxia in humans is associated with improved redox homeostasis and structural-functional adaptations of the neurovascular unit.The Journal of physiology · 2023Article
- Flipping Off and On the Redox Switch in the Microcirculation.Annual review of physiology · 2023Review
- Cerebral OJournal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2023Article
- The role of globins in cardiovascular physiology.Physiological reviews · 2022Review
- The enzymatic function of the honorary enzyme: S-nitrosylation of hemoglobin in physiology and medicine.Molecular aspects of medicine · 2022Review
- Red Blood Cell and Endothelial eNOS Independently Regulate Circulating Nitric Oxide Metabolites and Blood Pressure.Circulation · 2021Article
- Comodulation of NO-Dependent Vasodilation by Erythroid Band 3 and Hemoglobin: A GP.Mur Athlete Study.Frontiers in cardiovascular medicine · 2021Article
Corrections and comments
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Authors and funding
11 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundThe mechanisms underlying red blood cell (RBC)-mediated hypoxic vasodilation remain controversial, with separate roles for nitrite () and S-nitrosohemoglobin (SNO-Hb) widely contested given their ability to transduce nitric oxide bioactivity within the microcirculation. To establish their relative contribution in vivo, we quantified arterial-venous concentration gradients across the human cerebral and femoral circulation at rest and during exercise, an ideal model system characterized by physiological extremes of O
methodsTen healthy participants (5 men, 5 women) aged 24±4 (mean±SD) years old were randomly assigned to a normoxic (21% O
resultsHypoxia was associated with a mild increase in both cerebral blood flow and femoral blood flow (P<0.05 versus normoxia) with further, more pronounced increases observed in femoral blood flow during exercise (P<0.05 versus rest) in proportion to the reduction in RBC oxygenation (r=0.680-0.769, P<0.001). Plasma gradients reflecting consumption (arterial>venous; P<0.05) were accompanied by RBC iron nitrosylhemoglobin formation (venous>arterial; P<0.05) at rest in normoxia, during hypoxia (P<0.05 versus normoxia), and especially during exercise (P<0.05 versus rest), with the most pronounced gradients observed across the bioenergetically more active, hypoxemic, and acidotic femoral circulation (P<0.05 versus cerebral). In contrast, we failed to observe any gradients consistent with RBC SNO-Hb consumption and corresponding delivery of plasma S-nitrosothiols (P>0.05).
conclusionsThese findings suggest that hypoxia and, to a far greater extent, exercise independently promote arterial-venous delivery gradients of intravascular nitric oxide, with deoxyhemoglobin-mediated reduction identified as the dominant mechanism underlying hypoxic vasodilation.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.