Oxygen Toxicity: Mechanisms in Humans

Study Overview
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Brief Summary
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The goal of this clinical trial is to learn about the mechanisms of oxygen toxicity in scuba divers. The main questions it aims to answer are: How does the training of respiratory muscles affect oxygen toxicity? How do environmental factors, such as sleep deprivation, the ingestion of commonly utilized medications, and chronic exposure to carbon dioxide, impact the risk of oxygen toxicity? How does immersion in water affect the development of oxygen toxicity? Participants will be asked to do the following: Undergo a basic screening exam composed of health history, vital signs, and some respiratory function tests Train their respiratory muscles at regular intervals Exercise on a cycle ergometer both in dry conditions and underwater/under pressure in the context of medication, sleep deprivation, or carbon dioxide exposure Researchers will compare the performance of each subject before and after the possible interventions described above to see if there are changes in exercise performance, respiratory function, cerebral blood flow, and levels of gene expression.

Official Title
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Applied Physiology of Oxygen Toxicity: Mechanisms in Humans

Conditions
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Oxygen Toxicity, Hypercapnia, Seizures

Intervention / Treatment
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* Behavioral: Sleep Deprivation
* Drug: Caffeine
* Drug: Methylphenidate
* Drug: Carbon Dioxide


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Equal numbers of male and female Non-smokers Aged 18-45 years Males will be required to have VO2 peak > or equal to mL/kg min and females > or equal to 30 mL/kg min Exclusion Criteria: Pregnancy Cardiorespiratory disease, including hypertension Neuromuscular disease Anemia History of hemoglobinopathy, including sick cell disease and trait

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 45 Years

Sexes Eligible for Study
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All

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: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Sleep Deprivation<br>Effect of sleep deprivation on HCVR and arterial PCO2 during submersed rest and exercise at 98 fsw. Ten subjects will be tested before and after 24 hours of sleep deprivation. The order of sleep deprivation vs. control will be randomized. Measurements at 98 fsw will be obtained at rest and during 10 minutes of moderate exercise in thermoneutral (29-30°C) water. | Behavioral: Sleep Deprivation<br>* 24 hours sleep deprivation<br>|
| Experimental: Caffeine<br>Effect of caffeine and methylphenidate on HCVR and arterial PCO2 during submersed rest and exercise at 98 fsw. Twenty subjects will be similarly sleep-deprived, tested as above and then re-tested tested following oral administration of administration of either oral caffeine (N=10) or methylphenidate (N=10). Pre-dive caffeine will be administered 500 mg orally [59]. Pre-dive methylphenidate will be administered as a single dose of 5 mg [60]. The order of drug administration vs. control will be randomized. Measurements at 98 fsw will be obtained at rest and during 10 minutes of moderate exercise in thermoneutral (29-30°C) water. fNIRS will be used to assess cerebral oxygenation and regional blood volume. | Drug: Caffeine<br>* Oral administration of caffeine<br>|
| Experimental: Methylphenidate<br>Effect of caffeine and methylphenidate on HCVR and arterial PCO2 during submersed rest and exercise at 98 fsw. Twenty subjects will be similarly sleep-deprived, tested as above and then re-tested tested following oral administration of administration of either oral caffeine (N=10) or methylphenidate (N=10). Pre-dive caffeine will be administered 500 mg orally [59]. Pre-dive methylphenidate will be administered as a single dose of 5 mg [60]. The order of drug administration vs. control will be randomized. Measurements at 98 fsw will be obtained at rest and during 10 minutes of moderate exercise in thermoneutral (29-30°C) water. fNIRS will be used to assess cerebral oxygenation and regional blood volume. | Drug: Methylphenidate<br>* Oral administration of methylphenidate<br>|
| Experimental: Carbon Dioxide Exposure<br>Effect of simulated chronic CO2 exposure on HCVR and arterial PCO2 during submersed rest and exercise at 98 fsw. Ten subjects will be studied before and after induction of metabolic alkalosis as described above with daily oral administration of sodium bicarbonate. Oral bicarbonate to simulate hypercapnia exposure will seek to increase serum bicarbonate to 30 mM/L via daily oral intake of 6 teaspoons of NaHCO3 for five days. Subsequently, blood will be drawn and intake adjusted as necessary [61]. The order of alkalization vs. control will be randomized. Measurements at 98 fsw will be obtained at rest and during 10 minutes of moderate exercise in thermoneutral (29-30°C) water. | Drug: Carbon Dioxide<br>* Oral administration of sodium bicarbonate to simulate carbon dioxide exposure<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Hypercapnic ventilatory response |  | 3 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Lactate, pyruvate |  | 3 months | 
| Arterial PCO2 |  | Baseline and after Intervention/arm | 
| Integrated diaphragmatic function (IDF) composite score | A composite score comprised of maximum breathing capacity (MBC), maximum inspiratory pressure (MIP), maximum expiratory pressure (MEP), and diaphragmatic thickness will be used as the measure of Integrated diaphragmatic function (IDF). | Baseline and after Intervention/arm, which averages 3 months | 
| Cerebral blood oxygenation |  | Baseline and after Intervention/arm, which averages 3 months | 
| Hormone levels (leptin, adiponectin) |  | Baseline and after Intervention/arm, which averages 3 months |