Influence of Intermittent Hypoxia on Loop Gain in Healthy Subjects

Sleep apnoea-hypopnoea syndrome (SAHOS), which causes numerous comorbidities, particularly cardiovascular ones, is widespread worldwide today and incurs significant healthcare costs. Current research in this field focuses on identifying different phenotypes in affected patients in order to provide more personalised treatment. One of these phenotypes appears to be linked to instability in ventilatory control due to an increase in loop gain (LG) in these subjects. However, the pathophysiology of this ventilatory control instability due to increased LG is not fully understood. It is still difficult to determine whether subjects have an intrinsically high LG or if exposure to intermittent hypoxia during OSA promotes an increase in LG. It has also been demonstrated that OSA causes vascular hyperreactivity by increasing oxidative stress through elevated ROS production. This leads to endothelial dysfunction in response to intermittent hypoxia associated with apnoea. Extracellular vesicles (microvesicles and exosomes) have been shown to play a role in this endothelial response. These extracellular vesicles are essential for intercellular communication in both physiological and pathological situations, such as SAHOS. Therefore, the objective of this research is to determine whether exposure to intermittent hypoxia and changes in microvesicle phenotype could influence LG, which could lead to new therapeutic advances in the context of SAHOS.

Inclusion Criteria: * Healthy subjects aged 18 to 45 * BMI between \[18-25\] kg/m2 * No known sleep disorders * Free subjects, not under guardianship or curatorship or subordination * Persons affiliated with or beneficiaries of a Social Security scheme * Signature of informed consent after clear and honest information about the study Non-inclusion Criteria: * Active smoking or cessation within the last 3 months and total consumption \> 10 pack-years * Alcohol or drug addiction * Excessive coffee consumption (\> 3 espressos/day) * History of acute mountain sickness (presence of symptoms such as dizziness, headaches, nausea/vomiting, and incapacitating fatigue during or after a stay at high altitude) * Living at high altitude (above 3,000 meters, continuously for more than 6 months during the last 10 years) * History of respiratory and/or cardiovascular and/or renal and/or neurological disease (migraines, epilepsy) * Diabetes * Anemia, sickle cell anemia * Any medication associated with oxygen metabolism and any psychotropic medication (anxiolytics, sedatives, antidepressants, neuroleptics, muscle relaxants, etc.) that may interfere with motor and respiratory control, muscle strength, or sleep quality * Women of childbearing age who do not use effective contraception (hormonal/mechanical: oral, injectable, transcutaneous, implantable, intrauterine device, or surgical: tubal ligation, hysterectomy, total ovariectomy) * Concurrent participation in another clinical research study affecting respiratory control or respiratory muscles * Persons benefiting from enhanced protection, namely minors, persons deprived of their liberty by judicial or administrative decision, persons staying in a healthcare facility Post-inclusion exclusion criteria: * SpO2 \< 97% in ambient air at rest. * Detection of pregnancy in women of childbearing age. * Detection of acute mountain sickness (Lake Louise score \> 0). * Abnormalities in spirometry, ventilatory polygraphy, electrocardiogram, and/or hemoglobinometry prior to randomization. * Ventilation minute signal, PETCO2 or PETO2 unusable. * Irreversible deterioration in the volunteer's health during the study period, likely to affect the experimental conditions.