The aim of this study is to investigate the effect of pre-acclimatization in a nitrogen tent at home, ventilated with a slightly increased nitrogen percentage, in preparation for an expedition at extreme altitude. Specifically, the current study aims to gather knowledge, whether pre-acclimatization, first, leads to improved capillary function during an expedition to extreme altitude, and second, affects incidence of altitude sickness and the likelihood of reaching the expedition destination without oxygen supplementation.

The project will be carried out in two phases corresponding to two randomized controlled trials in healthy volunteers, who are participating in an expedition at extreme altitudes with or without pre-acclimatization.

Expeditions to the world's highest peaks are attempted by increasing numbers of alpinists, taking advantage of broad commercial support. At extreme altitude successful functioning, and even survival, are only possible with adequate acclimatization, which consists of time-consuming exposure to gradually higher sleeping altitudes. Generally, an increase in 300-600 m per day at altitudes above 3000 m, and the minimization of cumulative time spend above 6500 m, are considered safe practice. Mainly in an attempt to accelerate expeditions to extreme altitudes, a preacclimatization technique using nitrogen concentration tent induced normobaric hypoxia is increasingly employed in practice, and already part commercial expedition plans. Some previous research indicates that intermittent normobaric hypoxia may reduce the incidence of acute mountain sickness, while the results from other studies remain inconclusive or negative. One study has not found serious adverse effects related to intermittent normobaric hypoxia, such as high-altitude pulmonary or cerebral edema.

Thus, despite the emergence of increasing numbers of commercial expedition programs making use of nitrogen concentration tent preacclimatization protocols, many factors remain unclear. Next to remaining uncertainties regarding the extent of the hypoxic condition induced by these devices, current data does not allow adequate conclusions regarding the choice of optimal preacclimatization protocol, optimal associated ascent profiles, and possible effects on oxygen delivery capacity to the tissue, incidence of high-altitude related disease, and even summit success. Thus, the present study aims to conduct a randomized controlled trial to assess the efficacy of nitrogen concentration tent preacclimatization as part of two expeditions to extreme altitude. The immediate effects of nitrogen concentration tent preacclimatization are assessed through continuous monitoring of oxygen partial pressure in the tent and the hemoglobin oxygen saturation throughout preacclimatization. To test whether preacclimatization is associated with physiologic adaptation, tissue red blood cell perfusion as a main contributor to increase oxygen delivery capacity in the microcirculation throughout acclimatization to extreme altitude, is assessed using non-invasive handheld vital microscopy during preacclimatization and throughout the expedition, and the incidence and severity of high-altitude related disease and summit success, are recorded during the expeditions.

Inclusion Criteria:

• Healthy
• Active alpinists (active alpinists denotes individuals with regular experience in alpine high mountain climbing in rock, ice and snow terrain of difficulty WS - ZS according to the Swiss Alpine Club (SAC-CAS) grading scale assessed in a self-reporting questionnaire
• age > 18 years

Exclusion Criteria:

• history of high-altitude pulmonary edema or cerebral edema
• pregnancy or lactation
• heart failure (AHA Stage B and above)
• pulmonary hypertension
• pulmonary disease excluding mild bronchial asthma
• chronic kidney failure (KDIGO Stage 1 and above)
• chronic liver disease
• subjects with a history of smoking (> 5 PY), and high familiar predisposition for cardiovascular disease, when combined with smoking