title: Energy metabolism and the high-altitude environment.
abstract: At high altitude the barometric pressure falls, challenging oxygen delivery to the tissues. Thus, whilst hypoxia is not the only physiological stress encountered at high altitude, low arterial P(O2) is a sustained feature, even after allowing adequate time for acclimatization. Cardiac and skeletal muscle energy metabolism is altered in subjects at, or returning from, high altitude. In the heart, energetic reserve falls, as indicated by lower phosphocreatine-to-ATP ratios. The underlying mechanism is unknown, but in the hypoxic rat heart fatty acid oxidation and respiratory capacity are decreased, whilst pyruvate oxidation is also lower after sustained hypoxic exposure. In skeletal muscle, there is not a consensus. With prolonged exposure to extreme high altitude (>5500 m) a loss of muscle mitochondrial density is seen, but this was not observed in a simulated ascent of Everest in hypobaric chambers. At more moderate high altitude, decreased respiratory capacity may occur without changes in mitochondrial volume density, and fat oxidation may be downregulated, although this is not seen in all studies. The underlying mechanisms, including the possible role of hypoxia-signalling pathways, remain to be resolved, particularly in light of confounding factors in the high-altitude environment. In high-altitude-adapted Tibetan natives, however, there is evidence of natural selection centred around the hypoxia-inducible factor pathway, and metabolic features in this population (e.g. low cardiac phosphocreatine-to-ATP ratios, increased cardiac glucose uptake and lower muscle mitochondrial densities) share similarities with those in acclimatized lowlanders, supporting a possible role for the hypoxia-inducible factor pathway in the metabolic response of cardiac and skeletal muscle energy metabolism to high altitude.
authors: Department of Physiology, Development and Neuroscience, University of Cambridge, Cambridge, UK.
authors: Andrew J
authors: AJ
authors: Murray
mesh_terms: D000064:Acclimatization / Q000502:physiology; D000399:Air Pressure; D000531:Altitude; D000818:Animals; D004734:Energy Metabolism / Q000502:physiology*; D006321:Heart / Q000502:physiology; D006801:Humans; D018482:Muscle, Skeletal / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism