Cellular P O 2 as a determinant of maximal mitochondrial O₂consumption in trained human skeletal muscle

Abstract

Previously, by measuring myoglobin-associated PO(2) (P(Mb)O(2)) during maximal exercise, we have demonstrated that 1) intracellular PO(2) is 10-fold less than calculated mean capillary PO(2) and 2) intracellular PO(2) and maximum O(2) uptake (VO(2 max)) fall proportionately in hypoxia. To further elucidate this relationship, five trained subjects performed maximum knee-extensor exercise under conditions of normoxia (21% O(2)), hypoxia (12% O(2)), and hyperoxia (100% O(2)) in balanced order. Quadriceps O(2) uptake (VO(2)) was calculated from arterial and venous blood O(2) concentrations and thermodilution blood flow measurements. Magnetic resonance spectroscopy was used to determine myoglobin desaturation, and an O(2) half-saturation pressure of 3.2 Torr was used to calculate P(Mb)O(2) from saturation. Skeletal muscle VO(2 max) at 12, 21, and 100% O(2) was 0.86 +/- 0.1, 1.08 +/- 0.2, and 1.28 +/- 0.2 ml. min(-1). ml(-1), respectively. The 100% O(2) values approached twice that previously reported in human skeletal muscle. P(Mb)O(2) values were 2.3 +/- 0.5, 3.0 +/- 0.7, and 4.1 +/- 0.7 Torr while the subjects breathed 12, 21, and 100% O(2), respectively. From 12 to 21% O(2), VO(2) and P(Mb)O(2) were again proportionately related. However, 100% O(2) increased VO(2 max) relatively less than P(Mb)O(2), suggesting an approach to maximal mitochondrial capacity with 100% O(2). These data 1) again demonstrate very low cytoplasmic PO(2) at VO(2 max), 2) are consistent with supply limitation of VO(2 max) of trained skeletal muscle, even in hyperoxia, and 3) reveal a disproportionate increase in intracellular PO(2) in hyperoxia, which may be interpreted as evidence that, in trained skeletal muscle, very high mitochondrial metabolic limits to muscle VO(2) are being approached.

Reduced muscle oxidative capacity is independent of O2 availability in elderly people

“…3) also suggests that, in normoxia, the diffusion of O 2 from capillary to mitochondria is able to compensate for the reduction in convective O 2 delivery commonly associated with aging (Proctor and Parker 2006). If true, this increased O 2 diffusion during exercise in the elderly would then result in a preserved intracellular O 2 pressure (iPO 2 ), which drives mitochondrial respiration (Wilson et al 1977;Richardson et al 1999;Richardson et al 1995). In line with this possibility, O 2 diffusing capacity appears to be well preserved in the elderly as the capillary to fiber area ratios is maintained (Chilibeck et al 1997;Proctor et al 1995) and may actually be increased when capillary to fiber area is normalized for mitochondrial volume (Mathieu-Costello et al 2005).…”

Maximum aerobic performance in lines ofMusselected for high wheel-running activity: effects of selection, oxygen availability and the mini-muscle phenotype

“…Accordingly, previous studies have reported relatively minor increases in V O 2 max with increased O 2 delivery (Spriet et al, 1986;Lindstedt et al, 1988;Richardson et al, 1999;Lindstedt and Conley, 2001), which suggests that O 2 delivery was enhanced beyond the capacity of mitochondria to metabolize the O 2 available. Although it is possible that mitochondrial capacity might be reaching its limit in 30% O 2 (e.g.…”

“…Factors limiting maximum O 2 uptake may be broadly broken into four categories: (1) pulmonary diffusing capacity, (2) maximum cardiac output, (3) oxygen transport in the blood and (4) skeletal muscle characteristics (Wagner, 1996;Richardson et al, 1999;Bassett and Howley, 2000;see Hochachka, 2003, for details of O 2 transport within cells). According to Fick's law of diffusion and the Fick principle, the relative importance of each of these factors in determining V O 2 max may vary at different atmospheric P O 2.…”

“…Although it is possible that mitochondrial capacity might be reaching its limit in 30% O 2 (e.g. Richardson et al, 1999 in humans at 100% P O 2), two lines of evidence suggest that V O 2 max in S and C lines under normal conditions (i.e. normoxia) is constrained by pulmonary and cardiovascular systems.…”

“…Effects of hyperoxia on V O 2 max are not as straightforward, because limitations at different levels in the O 2 cascade may lead to different experimental outcomes (Richardson et al, 1999;Lindstedt and Conley, 2001;Noakes et al, 2001). Increased V O 2 max in hyperoxia may suggest that O 2 uptake and delivery systems are more relevant for V O 2 max in normoxia than mitochondrial oxidative capacity (i.e.…”