It has been shown in in vitro and animal models that hypoxia can have pro-inflammatory effects and hyperoxia can have anti-inflammatory effects. The pro-inflammatory effect could be the result of activation of Hypoxia Inducible Factor, a transcription factor that is known to activate many cell systems aimed at cell survival, including the inflammatory response. The anti-inflammatory effects of hyperoxia could be the annihilation of Hypoxia Inducible Factor, but also a decrease in inflammation due to oxygen toxicity resulting in a decrease in clearance of pathogens. These effects have been sparsely studied in humans. Therefore, we hypothesize that hypoxia results in an increase in Hypoxia Inducible Factor in circulating leukocytes and increases inflammatory reactions, whereas hyperoxia decreases these reactions.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
BASIC_SCIENCE
Masking
NONE
Enrollment
20
Subjects will be breathing an individualized mix of nitrogen and room air titrated to an oxygen saturation of 80-85%.
Subjects will be breathing 100% oxygen
Intensive Care Medicine, Radboud University Nijmegen Medical Centre
Nijmegen, Nijmegen, Gelderland, Netherlands
Hypoxia Inducible Factor 1 alpha in circulating leukocytes
Hypoxia Inducible Factor 1 alpha in circulating neutrophils, lymphocytes and monocytes as measured with flow cytometry
Time frame: 24 hours
Hypoxia Inducible Factor mRNA and anti Hypoxia Inducible Factor mRNA in circulating leukocytes
Time frame: 24 hours
Reactive Oxygen Species in circulating leukocytes
ROS in circulating leukocytes, subclassified in neutrophils and monocytes
Time frame: 24 hours
Phagocytic function of circulating leukocytes
Time frame: 24 hours
cytokine production after ex vivo stimulation of leukocytes
Time frame: 24 hours
circulating cytokines (including but not limited to IL-6, IL-10, IL-1RA)
Time frame: 24 hours
Hemodynamic parameters
Blood pressure, heart frequency, cardiac output measurement
Time frame: 24 hours
ventilatory response
Measures of ventilation: respiratory rate, blood gas changes
Time frame: 24 hours
adenosine metabolism
urine and plasma adenosine,adenosine receptor mRNA, purines
Time frame: 24 hours
alkaline phosphatase
Time frame: 24 hours
cognitive function
neuropsychologic assessment of cognitive function
Time frame: 24 hours
Hepcidin and iron parameters
Time frame: 24 hours
catecholamines
adrenaline, noradrenaline and dopamine
Time frame: 24 hours
Neutrophil function
Time frame: 24 hours
body temperature
Time frame: 24 hours
oxygen saturation and PaO2
Time frame: 24 hours
subjective symptoms
Time frame: 24 hours
high sensitive troponin
Time frame: 24 hours
iFABP
Time frame: 24 hours
Brain specific proteins
Time frame: 24 hours
endocan
Time frame: 24 hours
adrenomedullin
Time frame: 24 hours
EPO
Time frame: 24 hours
VEGF
Time frame: 24 hours
Heart rate variability
Time frame: 24 hours
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