The role of O2 supply in muscle fatigue

It is well established that altering O-2 delivery to contracting skeletal muscle affects human performance. In this respect, a reduced O-2 supply (e.g., hypoxia) increases the rate of muscle fatigue, whereas increasing O-2 supply (e.g., hyperoxia) reduces the rate of fatigue. Interestingly, the faster onset of fatigue in moderate hypoxia does not appear to be a consequence of mitochondrial O-2 limitation because these effects occur at submaximal rates of O-2 consumption for these conditions and at O-2 tensions well above that which impairs mitochondrial O-2 uptake in vitro. Alterations in O-2 supply modulate the regulation of cellular respiration and may affect the onset of impaired Ca2+ handling with fatigue. Specifically, changes in O-2 supply alter the coupling between phosphocreatine hydrolysis and O-2 uptake in contracting muscles, which by determining the rate of inorganic phosphate (Pi) accumulation may affect Ca2+ release. Partial ischemia differs somewhat in that the reduction in force could be due to reduced O-2 supply and/or impaired removal of metabolic by-products secondary to insufficient blood flow. Nonetheless, recent evidence shows a parallel decline and restoration of force with alterations in O-2 supply but not blood flow alone during submaximal contractions. Furthermore, the causes of fatigue are similar when O-2 is plentiful and when it is reduced.