Limiting factors to oxygen transport on Mount Everest 30�years after: a critique of Paolo Cerretelli?s contribution to the study of altitude physiology

Abstract

In 1976, Paolo Cerretelli published an article entitled "Limiting factors to oxygen transport on Mount Everest" in the Journal of Applied Physiology. The paper demonstrated the role of cardiovascular oxygen transport in limiting maximal oxygen consumption (VO2max). In agreement with the predominant view of VO2max limitation at that time, however, its results were taken to mean that cardiovascular oxygen transport does not limit VO2max at altitude. So it was argued that the limiting factor could be in the periphery, and muscle blood flow was proposed as a possible candidate. Despite this suggestion, the conclusion generated a series of papers on muscle structural characteristics. These experiments demonstrated a loss of muscle oxidative capacity in chronic hypoxia, and thus provided an unambiguous refutation of the then widespread hypothesis that an increased muscle oxidative capacity is needed at altitude to compensate for the lack of oxygen. This analysis is followed by a short account of Cerretelli's more recent work, with a special attention to the subject of the so-called "lactate paradox".

Changes in mitochondrial enzymatic activities of monocytes during prolonged hypobaric hypoxia and influence of antioxidants: A randomized controlled study

“…35,36 Contrasting this regulatory process in immune cells at high altitudes and in sepsis is the loss of mitochondrial structure -rather than functional change of the mitochondrial activity -in muscle cells at high altitudes. [25][26][27][28][29] In our study, antioxidant dietary supplements did not have any effect on the observed mitochondrial abnormalities. In human subjects at high altitude, results of trials on antioxidative treatment have shown mixed results.…”

“…Examining subjects before and after high-altitude exposure, different authors found decreases in enzyme activities of aerobic-oxidative metabolism which were related to decrements in mitochondrial volume density, suggesting a cellular loss of mitochondrial structure rather than qualitative changes of the mitochondrial function. [25][26][27][28][29] In these subjects, significant reduction of muscle-fiber cross-sectional area, and an unchanged capillary-to-muscle-fiber ratio and therefore increased capillary density, have been reported. The effect of hypoxic exposure on citrate synthase activity which is a marker of mitochondrial volume density and oxidative capacity remains controversial.…”

Metabolic adaptation of skeletal muscle to high altitude hypoxia: how new technologies could resolve the controversies

“…Mitochondrial volume density is consistently and substantially decreased in the skeletal muscle of climbers acclimatizing to high altitude [12,13], and was found to be lower in the muscles of Himalayan Sherpas than those of unacclimatized lowlanders [13]. Prolonged exposure to altitude is also associated with accumulation of lipofuscin in skeletal muscle [14], a lipid peroxidation product that may be indicative of mitochondrial damage.…”

Developmental plasticity of mitochondrial function in American alligators,Alligator mississippiensis

“…In particular, structural and functional remodeling of the mitochondria has emerged as a critical component of hypoxic survival (24, 53, 55). Mitochondrial volume density has been observed to decrease with chronic hypoxia in a range of adult vertebrates, and this is often associated with large-scale reductions in ETC Complex activities and aerobic capacity (15, 21, 24, 25, 33, 34, 42, 55, 56). Mitochondrial efficiency can be improved by CIV subunit switching which maximizes the yield of ATP per oxygen molecule consumed and minimizes the production of harmful ROS (23).…”