Neuromuscular fatigability at high altitude: Lowlanders with acute and chronic exposure, and native highlanders.

Ascent to high altitude is accompanied by a reduction in partial pressure of inspired oxygen, which leads to interconnected adjustments within the neuromuscular system. This review describes the unique challenge that such an environment poses to neuromuscular fatigability (peripheral, central and supraspinal) for individuals who normally reside near to sea level (SL) (<1000 m; ie, lowlanders) and for native highlanders, who represent the manifestation of high altitude-related heritable adaptations across millennia. Firstly, the effect of acute exposure to high altitude-related hypoxia on neuromuscular fatigability will be examined. Under these conditions, both supraspinal and peripheral fatigability are increased compared with SL. The specific mechanisms contributing to impaired performance are dependent on the exercise paradigm and amount of muscle mass involved. Next, the effect of chronic exposure to high altitude (ie, acclimatization of ~7-28 days) will be considered. With acclimatization, supraspinal fatigability is restored to SL values, regardless of the amount of muscle mass involved, whereas peripheral fatigability remains greater than SL except when exercise involves a small amount of muscle mass (eg, knee extensors). Indeed, when whole-body exercise is involved, peripheral fatigability is not different to acute high-altitude exposure, due to competing positive (haematological and muscle metabolic) and negative (respiratory-mediated) effects of acclimatization on neuromuscular performance. In the final section, we consider evolutionary adaptations of native highlanders (primarily Himalayans of Tibet and Nepal) that may account for their superior performance at altitude and lesser degree of neuromuscular fatigability compared with acclimatized lowlanders, for both single-joint and whole-body exercise.