Hyperoxia, Hypoxia
Conditions
Keywords
Oxygen, Hypoxia, Hyperoxia, Inflammation, Innate immunity
Brief summary
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.
Interventions
OTHERHypoxia
Subjects will be breathing an individualized mix of nitrogen and room air titrated to an oxygen saturation of 80-85%.
OTHERHyperoxia
Subjects will be breathing 100% oxygen
Sponsors
Radboud University Medical Center
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
18 Years to 35 Years
Healthy volunteers
Yes
Inclusion criteria
* Age ≥18 and ≤35 yrs * Male * Healthy
Exclusion criteria
* Use of any medication * Smoking * History, signs or symptoms of cardiovascular disease * History of atrial or ventricular arrhythmia * (Family) history of myocardial infarction or stroke under the age of 65 years * Cardiac conduction abnormalities on the ECG consisting of a 2nd degree atrioventricular block or a complex bundle branch block * Hypertension (defined as RR systolic \> 160 or RR diastolic \> 90 mmHg) * Hypotension (defined as RR systolic \< 100 or RR diastolic \< 50 mmHg) * Renal impairment (defined as plasma creatinine \>120 μmol/l) * Liver enzyme abnormalities alkaline phosphatase\>230 U/L and/or ALT\>90 U/L * Medical history of any obvious disease associated with immune deficiency * CRP \> 20 mg/L, WBC \> 12x109/L, or clinically significant acute illness, including infections, within 4 weeks before endotoxemia day * Participation in a drug trial or donation of blood 3 months prior to the experiment * Pre-existent lung disease or asthma * Use of recreational drugs within 21 days prior to experiment day * Visit to altitude \>1500m within 4 weeks prior to the experiment * Air travel with flight time over 3 hours within 4 weeks prior to the experiment * History of acute mountain sickness * Recent hospital admission or surgery with general anaesthesia (\<3 months) * Claustrophobia * Feelings of discomfort during a 10 minute test wearing the transparent respiratory helmet at the screening visit
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Hypoxia Inducible Factor 1 alpha in circulating leukocytes | 24 hours | Hypoxia Inducible Factor 1 alpha in circulating neutrophils, lymphocytes and monocytes as measured with flow cytometry |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Hypoxia Inducible Factor mRNA and anti Hypoxia Inducible Factor mRNA in circulating leukocytes | 24 hours | — |
| Reactive Oxygen Species in circulating leukocytes | 24 hours | ROS in circulating leukocytes, subclassified in neutrophils and monocytes |
| Phagocytic function of circulating leukocytes | 24 hours | — |
| cytokine production after ex vivo stimulation of leukocytes | 24 hours | — |
| circulating cytokines (including but not limited to IL-6, IL-10, IL-1RA) | 24 hours | — |
| Hemodynamic parameters | 24 hours | Blood pressure, heart frequency, cardiac output measurement |
| adenosine metabolism | 24 hours | urine and plasma adenosine,adenosine receptor mRNA, purines |
| alkaline phosphatase | 24 hours | — |
| cognitive function | 24 hours | neuropsychologic assessment of cognitive function |
| Hepcidin and iron parameters | 24 hours | — |
| catecholamines | 24 hours | adrenaline, noradrenaline and dopamine |
| ventilatory response | 24 hours | Measures of ventilation: respiratory rate, blood gas changes |
| body temperature | 24 hours | — |
| oxygen saturation and PaO2 | 24 hours | — |
| subjective symptoms | 24 hours | — |
| high sensitive troponin | 24 hours | — |
| iFABP | 24 hours | — |
| Brain specific proteins | 24 hours | — |
| endocan | 24 hours | — |
| adrenomedullin | 24 hours | — |
| EPO | 24 hours | — |
| VEGF | 24 hours | — |
| Heart rate variability | 24 hours | — |
| Neutrophil function | 24 hours | — |
Countries
Netherlands
Outcome results
None listed