INTRODUCTION:
Physical exertion under acute hypoxic conditions leads to a progressive reduction in oxygen saturation (SpO₂). This event, in turn, further exacerbates oxidative stress and inflammatory responses, often leading to cellular oxidative damage at different organ/tissue levels. Exposure above 4,000 m altitude is frequently associated with the so-called acute mountain sickness (AMS), a syndrome reflecting the substantial physiological strain imposed by high-altitude environments, yet its neuro-endocrine and molecular mechanisms remain elusive.
METHODS:
Using a non-invasive saliva and urine sampling approach, we tested the impact of high altitude on a neuroendocrine portfolio (cortisol, dopamine, and BDNF levels) and a redox-inflammatory portfolio. The latter consisted of the evaluation of redox markers, such as lipid peroxidation, 8-isoprostane, total antioxidant capacity (TAC), and glycation: RAGE, and pro-inflammatory and bactericidal proteins, such as interleukin 6 (IL-6) and surfactant Protein D (SP-D), respectively. Italian Air Force (AF) specialists (all males; n=9) were enrolled in the study during their mission (Artemis 4554) in the Italian Alps. The team walked from Alagna (T0) to the Rifugio Gnifetti (T1), then continued to Capanna Margherita (T2–T3), and finally returned to Alagna (T4). To assess the extent of AMS sickness, we used the subjective scale (VAS), and the Lake Louise Score (LLS).
RESULTS:
The AF specialists exhibited a marked increase in the extent of oxidative stress (8-iso =+151%; TAC=-41%) and inflammation (IL-6 = +244%) that peaked at 4558 m, when SaO2 plummeted. Concomitantly, cortisol levels rose (+13%), whereas dopamine and BDNF declined by -40 and 28%, respectively. During the mission, 4 cases (44%) of AMS (score >3) were reported, including 1 case at Rifugio Gnifetti that interrupted the ascent, and 3 cases at Capanna Margherita.
CONCLUSION:
Our data indicate that high-altitude exposure, i.e., hypobaric hypoxia, engages neuroendocrine pathways, resulting in reduced dopamine levels and BDNF concentrations that could underscore loss of cognitive capacity. At the same time, elevated cortisol levels, in conjunction with a pro-oxidative/inflammatory milieu, attest to stress conditions. When combined and prolonged, these factors can impair alertness, thus affecting the operational readiness/performance of military personnel operating at high altitudes.