Cytokine and Stress Hormone Responses to Exercise-induced Hypoxemia Among Endurance-trained

Study Overview
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Brief Summary
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It is well documented that exercise-induced arterial hypoxemia (EIAH) is highly prevalent among endurance-trained athletes performing heavy intensity exercise, regardless of sex and age. Although it has been shown that a drop in arterial oxyhemoglobin saturation (SaO2) during exercise (i.e. EIAH) negatively affects aerobic capacity measures such as VO2max and time trial performance, there remains a gap in the literature as to the physiological consequences of EIAH, and specifically acute cytokines and stress-related responses to hypoxemia during exercise. Exposure to hypoxic environments in which SaO2 is reduced and exercise can each, independently, alter/activate various pro- and anti-inflammatory markers and increases stress hormones. It follows then that EIAH athletes could be more susceptible to, and encounter more frequently, episodes of elevated levels of inflammatory cytokines and an exaggerated stress response than non-EIAH athletes; however, to the best of the investigators knowledge, this is yet to be confirmed. Therefore, it is hypothesized that highly trained endurance athletes who develop EIAH will experience more pronounced increases in inflammatory cytokines and stress hormones following a bout of heavy intensity exercise compared to athletes without EIAH.

Detailed Description
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Fifty highly trained endurance runners (men and women, age: 18-35 years) will be recruited for this study. The first testing session will serve as a screening tool to determine subject eligibility. Following the first testing sessions subjects will be divided into EIAH or non-EIAH groups based on SaO2 at VO2max (EIAH < 93%, non-EIAH > 95%; Dempsey and Wagner criteria). Subjects with intermediate SaO2 (93-95% at VO2max) values will be included in the study for correlational analyses only. All subjects will be advised orally, and in writing, as to the nature of the experiments and will give written, informed consent to the study protocol. Study Design & protocol: Subjects will be asked to visit the Exercise Performance Laboratory at the Sylvan Adams Sports Institute on three occasions. During the first visit subject will perform resting pulmonary function tests (PFTs) followed by a graded exercise test to exhaustion on either a motorized-treadmill for the determination of VO2max, degree of EIAH (SaO2 at VO2max) and maximal heart rate (HRmax). On the second visit, subjects will perform PFTs, followed by a brief warm-up run for 10 min at a moderate intensity equivalent to 60% of HRmax, as obtained from the incremental test and a 30-min trial at either half-marathon pace (HM30), designed to simulate a tempo workout often practiced by endurance runners. The third visit, conducted 24 hours after the 30-min trial, will include a blood draw only.

Official Title
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Effect of Exercise-induced Hypoxemia on Cytokine and Stress Hormone Responses Among Endurance-trained Athletes

Conditions
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Exercise-induced Arterial Hypoxemia

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 1) Physically active (minimum of 50 km running/week) and maximal oxygen consumption > 55 and 50 ml/kg-1/min-1 for men and women, respectively. 2) classified as low risk based on a medical questionnaire, body mass index and non-smoking status. 3) No history of pulmonary, metabolic and/or cardiovascular disease. 4) normal pulmonary function as defined by a ≥ 80% of predicted forced vital capacity (FVC), forced expired volume in one second (FEV1) and FEV1/FVC according the American Thoracic Society standards. Exclusion Criteria: Smoking and/or any pulmonary, metabolic and/or cardiovascular disease. maximal oxygen consumption lower than set criteria.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 35 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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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| EIAH athletes<br>Athletes with arterial oxyhemoglobin saturation at maximal exercise during a graded exercise test <93% | |
| Non-EIAH athletes<br>Athletes with arterial oxyhemoglobin saturation at maximal exercise during a graded exercise test >95% | |
| Intermediate EIAH athletes<br>Athletes with arterial oxyhemoglobin saturation at maximal exercise during a graded exercise test of 93-95% | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Inflammatory cytokines | Changes in Inflammatory cytokines (e.g. IL-6, IL-1b, IL-ra, IL-10) | Changes from baseline to immediately, 2 hour and 24 hour post 30 minutes run at half marathon pace (HM30) | 
| Inflammatory cytokine | Changes in Inflammatory cytokine TNF-a | Changes from baseline to immediately, 2 hour and 24 hour post 30 minutes run at half marathon pace (HM30) | 
| Changes in Cortisol level | Stress hormones | Changes from baseline to immediately, 2 hour and 24 hour post 30 minutes run at half marathon pace (HM30) | 
| Changes in epinephrine level | Stress hormones | Changes from baseline to immediately, 2 hour and 24 hour post 30 minutes run at half marathon pace (HM30) | 
| Changes in norepinephrine level | Stress hormones | Changes from baseline to immediately, 2 hour and 24 hour post 30 minutes run at half marathon pace (HM30) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in number of Neutrophiles |  | Changes from baseline to immediately, 2 hour and 24 hour post 30 minutes run at half marathon pace (HM30) | 
| Changes in number of lymphocytes |  | Changes from baseline to immediately, 2 hour and 24 hour post 30 minutes run at half marathon pace (HM30) | 
| Changes in number of monocytes |  | Changes from baseline to immediately, 2 hour and 24 hour post 30 minutes run at half marathon pace (HM30) | 
| Immune markers | Changes in basophiles count (number of) | Changes from baseline to immediately, 2 hour and 24 hour post 30 minutes run at half marathon pace (HM30) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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High intensity exercise, Endurance, Athletes, Desaturation, Stress response, Inflammatory markers