Myoglobin O2 desaturation during exercise. Evidence of limited O2 transport.

The assumption that cellular oxygen pressure (PO2) is close to zero in maximally exercising muscle is essential for the hypothesis that O2 transport between blood and mitochondria has a finite conductance that determines maximum O2 consumption. The unique combination of isolated human quadriceps exercise, direct measures of arterial, femoral venous PO2, and 1H nuclear magnetic resonance spectroscopy to detect myoglobin desaturation enabled this assumption to be tested in six trained men while breathing room air (normoxic, N) and 12% O2 (hypoxic, H). Within 20 s of exercise onset partial myoglobin desaturation was evident even at 50% of maximum O2 consumption, was significantly greater in H than N, and was then constant at an average of 51 +/- 3% (N) and 60 +/- 3% (H) throughout the incremental exercise protocol to maximum work rate. Assuming a myoglobin PO2 where 50% of myoglobin binding sites are bound with O2 of 3.2 mmHg, myoglobin-associated PO2 averaged 3.1 +/- .3 (N) and 2.1 +/- .2 mmHg (H). At maximal exercise, measurements of arterial PO2 (115 +/- 4 [N] and 46 +/- 1 mmHg [H]) and femoral venous PO2 (22 +/- 1.6 [N] and 17 +/- 1.3 mmHg [H]) resulted in calculated mean capillary PO2 values of 38 +/- 2 (N) and 30 +/- 2 mmHg(H). Thus, for the first time, large differences in PO2 between blood and intracellular tissue have been demonstrated in intact normal human muscle and are found over a wide range of exercise intensities. These data are consistent with an O2 diffusion limitation across the 1-5-microns path-length from red cell to the sarcolemma that plays a role in determining maximal muscle O2 uptake in normal humans.

High muscle blood flow in man: is maximal O2 extraction compromised?

During conventional cycle ergometry, as work rate (WR) is increased toward maximum, O2 extraction increases hyperbolically, typically achieving values of 80-90% at peak O2 uptake (VO2). In contrast, studies using isolated knee-extensor exercise report much higher mass-specific blood flows (Q) and lower maximal O2 extractions (approximately 70%), which have been interpreted as transit time limitation to O2 movement out of the muscle capillary. However, maximal achievable WR levels during conventional cycle ergometry are generally reached (over 10-15 min) after rapid increases in WR, whereas the reported knee-extensor studies have used only more lengthy protocols (45 min). The duration of these protocols may have prevented the attainment of high WR levels and thus high O2 extraction ratios. Accordingly, this investigation examined leg Q and O2 extraction responses during single-leg knee-extensor exercise incremented rapidly (steps of 15-25 W per 2- to 3-min interval), which produced fatigue in 13-15 min. Q and muscle VO2 increased linearly with WR to fatigue with Q-WR and VO2-WR slopes similar to those reported in previous knee-extensor studies. However, with the use of this protocol, very high maximal achievable WR [99 +/- 6 (SE) W] and muscle Q (385 +/- 26 ml.min-1 x 100 g-1) levels were attained, some 80% greater than previously reported. An O2 extraction of 84.6 +/- 2.1% was reached, giving a maximal VO2 of 60.2 +/- 5.8 ml.min-1 x 100 g-1. We conclude that, even under the high Q conditions of single-leg knee-extensor exercise, O2 extraction does not reach a plateau on the basis of short transit times and that previous conclusions to the contrary reflect failure to attain sufficiently high WR levels. Maximal VO2, Q, and O2 extraction in this model have yet to be defined.