SUMMARY Human endurance performance is often evaluated on the basis of the maximal rate of oxygen uptake during exercise (V̇ O 2 max ). Methods for overcoming limits to V̇ O 2 max are touted as means for increasing athletic endurance performance. Here, we argue that the respiratory system is well designed for delivering O 2 to meet O 2 demands and that no single factor is rate-determining for O 2 uptake. We show that V̇ O 2 max can vary 5000-fold among mammals, while any limitation to O 2 delivery by a single component of the respiratory system affects V̇ O 2 max by 10% or less. Attempts to increase O 2 delivery by enhancing one step in the respiratory system are shown to have little effect. Blood doping, hyperoxia and O 2 supplementation of high-altitude natives all raise O 2 availability substantially to the working muscles, but these treatments increase V̇ O 2 max only minimally. Finally, we argue that O 2 uptake is only one of a number of properties important to human aerobic performance.

The mean minimal transit time for blood in muscle capillaries (tc) was estimated in six species, spanning two orders of magnitude in body mass and aerobic capacity: horse, steer, dog, goat, fox and agouti. Arterial (CaO2) and mixed venous (CvO2) blood O2 concentrations, blood hemoglobin concentrations ([Hb]) and oxygen uptake rates were measured while the animals ran on a treadmill at a speed that elicited the maximal oxygen consumption rate (VO2max) from each animal. Blood flow to the muscles (Qm) was assumed to be 85% of cardiac output, which was calculated using the Fick relationship. Total muscle capillary blood volume (Vc) and total muscle mitochondrial volume were estimated by morphometry, using a whole-body muscle sampling scheme. The tc was computed as Vc/Qm. The tc was 0.3-0.5 s in the 4 kg foxes and agoutis, 0.7-0.8 s in the 25 kg dogs and goats, and 0.8-1.0 s in the 400 kg horses and steers. The tc was positively correlated with body mass and negatively correlated with transcapillary O2 release rate per unit capillary length. Mitochondrial content was positively correlated with VO2max and with the product of Qm and [Hb]. These data suggested that Qm, Vc, maximal hemoglobin flux, and consequently tc, are co-adjusted to result in muscle O2 supply conditions that are matched to the O2 demands of the muscles at VO2max.

The quantitative structural composition of skeletal muscle tissue shows a wide range of variability among different species of animals and in any one species among muscles with a different function. Moreover, experimental manipulations such as exercise training or chronic electrical stimulation can dramatically change the ultrastructural appearance of the muscles involved. Both in endurance exercise and in chronic electrical stimulation the volume density of mitochondria can be increased greatly (by more than three-fold in the stimulation experiments). This happens without an apparent change of the internal architecture of the mitochondria, since the surface density of the inner mitochondrial membranes remains constant. In situations where both the mitochondrial volume and the maximal rate of oxygen consumption of the muscle tissue are known, these two variables are found to be linearly related. It can be calculated that the ‘maximal’ oxygen consumption of a unit volume of mitochondria in muscle is close to 5 ml O2 min-1 cm-3 under comparable conditions in man, mouse and a series of African mammals. It is hypothesized that there is a constant volume of oxygen metabolized per unit volume of mitochondria and unit time under limiting conditions in working skeletal muscle tissue. Given the efficiency of muscular energy conversion, this would allow an estimate of the potential for aerobic power production of a muscle from measurement of its volume density of mitochondria.