The Effects of Intermittent Hypoxia on Acute Hypoxic Injury

Acute exposure to hypoxia can induce acute hypoxic injury (AHI), according to the severity of the injury, it can be divided into acute mountain sickness (AMS), high altitude pulmonary edema (HAPE) and high altitude cerebral edema (HACE). AMS is the most common type, it mostly occurs within 6-12 hours after rapidly entering the altitude above 2500m, sometimes within 1h, and can be manifested as headache, nausea, diarrhea, sleep disorders, etc. The incidence of AMS at the altitude of 2500-3000m is 10-20%, which reaches 50-85% at 4500-5000m above sea level.

Intermittent hypoxia (IH) refers to periodic hypoxic-normoxic training performed with brief exposure to hypoxia. Previous studies have found that short-term intermittent hypoxia can increase the sensitivity of hypoxia and reduce the severity of acute hypoxia injury, and alleviate acute hypoxia injury by reducing the inflammatory response caused by hypoxia. Therefore, this study aims to conduct a randomized controlled trial to further reveal the effectiveness of IH and explore its potential mechanisms.

• Intermittent Hypoxia (Other): The intermittent hypoxia protocol refers to four cycles of 10 minutes hypoxia inhaling interval by 5 minutes normoxia, which is performed twice a day (at least 6 hours apart) in 5 days.
• Sham Intermittent Hypoxia (Other): The sham intermittent hypoxia protocol refers to 55 minutes normoxia inhaling, which is performed twice a day (at least 6 hours apart) in 5 days.

Primary outcomes

• Incidence of acute mountain sickness between IH group and control group [After the 6-hour acute hypoxia exposuring.]: A questionnaire called 2018 Lake Louise Scoring System (LLSS) score \[0-12\] will be used in this primary outcome assessment. The higher LLS scores mean the worse symptoms of acute mountain sickness (AMS).

Secondary outcomes

• Concentration of serum parameters between IH group and control group [After the 6-hour acute hypoxia exposuring.]
• Incidence of intracranial hypertension between IH group and control group [After the 6-hour acute hypoxia exposuring.]: A noninvasive cranial pressure detector will be used to monitor the intracranial pressure.
• Incidence of decreased reaction and executive ability between IH group and control group [After the 6-hour acute hypoxia exposuring.]: Related questionnaires will be used to assess the relevant cognitive domain.

Sex: All, ages: 18 Years to 45 Years, accepts healthy volunteers

Inclusion Criteria:

* Informed written consent from the volunteers.
* Healthy volunteers between ages of 18 and 45 years, body mass index (BMI) of 19.0 and 24.9 kg/m2.
* Long-term residence at flatland (altitude of <100 m), not having been to an altitude ≥1500 m in 30 days.
* Resting peripheral oxygen saturation of more than 90%, cerebral oxygen saturation between 58%-82%, heart rate between 60 bpm and 100 bpm, and blood pressure within the normal range (90-130/60-80 mmHg).

Exclusion Criteria:

* History of cardiovascular, cerebrovascular, pulmonary, hepatic, dermatologic, or hematologic diseases.
* History of substance abuse.
* The use of medications or medical devices.
* Pregnancy, hypertension, diabetes mellitus, obesity, sleep apnea and neurological disorders.