High Inspiratory Oxygen Fraction on Endothelial Function in Healthy Volunteers

Study Overview
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Brief Summary
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The frequency of preoperative cardiac ischemia and the 30-days postoperative mortality is much higher than previously assumed, with approximately 10 % of patients undergoing non-cardiac surgery suffering from postoperative myocardial injury. A recent danish study furthermore showed that patients treated with a high inspiratory oxygen fraction during surgery had a higher 1 year mortality compared with patients treated with a low inspiratory fraction. This was especially significant among patients undergoing cancer surgery. A possible explanation, is that a high oxygen fraction results in oxidative stress and endothelial dysfunction. With this randomized cross-over study we wish to investigate the effect of a high inspiratory oxygen fraction on the endothelial function among healthy male volunteers. The primary outcome is the endothelial function assessed by the EndoPat system. Secondary outcomes are changes in oxidative biomarkers. Heart rate variability (HRV) recordings will serve as a measure for the effect of oxygen on the autonomic nervous system.

Official Title
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Effect of High Inspiratory Oxygen Fraction on Endothelial Function in Healthy Volunteers: a Randomized Controlled Cross-over Trial

Conditions
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Endothelial Dysfunction

Intervention / Treatment
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* Other: 80% oxygen
* Other: 30% oxygen


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy male volunteers between 18 and 30 years who has given an oral and written informed consent Exclusion Criteria: Smoking, or ex-smoker Any kind of medication on a daily basis History of atopic dermatitis Known familiar hypercholesterolemia History of arteriosclerotic disease in the first and second-degree relatives Known or unknown arrhythmias, as measured by the baseline HRV-recording

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 30 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: 30% oxygen<br>Inhalation of 30% oxygen | Other: 30% oxygen<br> <br> |
| Experimental: 80% oxygen<br>Inhalation of 80% oxygen | Other: 80% oxygen<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Endothelial dysfunction assessed by the EndoPat-system | Changes in baseline pulse-wave-amplitude (PWA) after ischemia-reperfusion from the baseline PWA measurement until 5 minutes after ischemia as a measure of altered endothelial cell function caused by high inspiratory oxygen fractions | After 2 hours of preoxygenation | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Heart rate variability (HRV) after ischemia-reperfusion as a measure of altered balance in the Autonomic nervous system |  | Baseline measure conducted from baseline until 20 minutes of pre oxygenation. Secondary measures is conducted 20 minutes before withdrawal of the oxygen | 
| Plasma-Malondialdehyde (MDA) |  | Meaured at baseline, after 2 hours of oxygenation and after 30, 60, 120, 240 minutes after the EndoPat measure | 
| Plasma-Arginine/Asymmetric dimethylarginine(ADMA) |  | Meaured at baseline, after 2 hours of oxygenation and after 30, 60, 120, 240 minutes after the EndoPat measure | 
| Plasma-Tetrahydrobiopterin |  | Meaured at baseline, after 2 hours of oxygenation and after 30, 60, 120, 240 minutes after the EndoPat measure | 
| Plasma-Advanced oxidation protein products (AOPP) |  | Meaured at baseline, after 2 hours of oxygenation and after 30, 60, 120, 240 minutes after the EndoPat measure | 
| Plasma-Ascorbate/Dehydroascorbate (AA/DHA) |  | Meaured at baseline, after 2 hours of oxygenation and after 30, 60, 120, 240 minutes after the EndoPat measure | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Oxidative stress, Nitrogen oxide, Reactive oxygen species