Human aerobic performance: too much ado about limits to O2
1 Physiology and Functional Morphology Group, Department of Biological Sciences, Northern Arizona University, Flagstaff, AZ 86011-5640, USA and
2 Departments of Radiology, Physiology and Biophysics, and Bioengineering, University of Washington Medical Center, Seattle, WA 98195-7115, USA
*e-mail: Stan.Lindstedt{at}nau.edu
Accepted July 2, 2001
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Summary |
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Key words: oxygen delivery, oxygen transport cascade, O2max, human, aerobic performance, endurance
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Introduction |
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Underlying this approach is our belief that no single step in the O2 delivery cascade dictates total flux but rather that each step contributes to flux. This notion of shared flux control is common to current thinking in biochemical pathways (Fell and Thomas, 1995; Kascar and Burns, 1973), the concept of symmorphosis (Weibel and Taylor, 1981; Weibel et al., 1991) and a recent physical analysis of the cardiovascular system (West et al., 1999).
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Insights from the animal world |
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The human system is unique |
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O2max varies with mitochondrial content
An early study of muscle properties and O2max showed that mitochondrial volume density, Vv(mt,f), was proportional to
O2max from sedentary humans to athletes (Hoppeler et al., 1973). Exercise training studies seemed to contradict this proportionality by showing a 40% increase in quadriceps Vv(mt,f) but only a 15% increase in whole-body
O2max (Hoppeler et al., 1985). However, a quantitative comparison of the expected change in muscle versus whole-organism
O2max revealed the problem with this comparison of relative changes at the whole-body and muscle levels. The first step was to compare the changes that occurred at the level of the leg. This comparison showed that the increase in muscle power output agreed closely with the increase in muscle Vv(mt,f) with training. Thus, ATP use, as measured by leg power output, increased in proportion to the mitochondrial capacity for O2 uptake and ATP supply. The mitochondrial volume in the muscle increased as would be expected on the basis of the increased O2 demand for muscle power output. The second step was to compare O2 uptake estimated for the leg with whole-body
O2. This comparison revealed that the
O2 needed for this increase in power was close to the whole-body increase in
O2max that occurred with training. Thus, no discrepancy existed between changes at the level of the leg or between the leg and whole-body levels when the estimated change in
O2 at the leg was compared directly with the whole-body
O2 changes after training. This quantitative approach revealed that muscle mitochondrial volume, the estimated rate of O2 consumption and the actual rate of O2 uptake all increased proportionately with training. These results, and recent studies of sedentary subjects showing no increase in
O2max after breathing supplemental O2 (Cardus et al., 1998), suggest that
O2max reflects the muscle oxidative capacity recruited during exercise, as it does in quadrupedal mammals.
A quantitative approach also helps us understand the factors responsible for the decline in O2max with age. Elderly subjects show a large decline in
O2max relative to the young. A recent study showed that this decline in
O2max was accompanied by parallel changes in the oxidative capacity of the quadriceps muscle group with age (Conley et al., 2000). The end result was that a significant fraction of the decline in
O2max could be accounted for by the age-related change in the oxidative capacity of the quadriceps. In both adult and elderly subjects, the oxidative capacity of the quadriceps accounted for 30% of the whole-body rate of O2 uptake in accord with the fraction of quadriceps versus whole-limb power output during cycling. The implication of this study is clear: the drop in
O2max with age reflects the loss of O2-consuming muscle. This study demonstrates that the kind of quantitative O2 balance studies that have been accomplished in quadrupedal animals are also possible in humans even with the limitations of the bipedal gait. The result of this analysis in humans is the same as in quadrupeds: the range of
O2max corresponds quantitatively with the range of the oxidative capacity of muscle involved in exercise.
O2max varies with cardiovascular O2 delivery
Meeting the muscle O2 demand is the cardiovascular capacity for O2 delivery, which is determined by the product of cardiac output and O2 extraction. Both normally active and athletic subjects have similar and high (up to 90%) O2 extractions at O2max, and the increase in O2 delivery that underlies the twofold increase in
O2max results from an increase in cardiac output (see Fig.5.2)(Rowell, 1993). This difference in cardiac output is due to a higher stroke volume in athletes in accord with the larger heart of endurance-trained athletes. These findings indicate that a twofold difference in cardiovascular O2 delivery capacity underlies the twofold difference in
O2max between sedentary and athletic subjects.
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Limiting factors |
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Does oxygen delivery limit oxygen uptake or is it adequate to meet oxygen uptake?
Cardiovascular O2 delivery is the single identifiable factor most often implicated as the limit to oxygen uptake. Consequently, most of the recent drug scandals in endurance sports, starting with blood doping in the 1984 US Olympic cycling team, are designed to increase oxygen delivery. The current drug of choice, erythropoietin, can boost hematocrit dramatically and, until only recently, exogenous erythropoietin has been undetectable. This focus on boosting O2 delivery seems to assume that humans do not conform to the general pattern of balance among respiratory system capacities. It also begs the question of what is responsible for the remaining respiratory structures being over-built (i.e. possessing capacity in excess of need or demand) if cardiovascular O2 delivery is a single rate-limiting step.
One explanation for why cardiovascular O2 delivery is thought to limit O2max is that this step is the simplest to manipulate experimentally. Resultant correlations between rates of O2 delivery and
O2max have been interpreted as demonstrating a rate-limiting role of oxygen delivery. On the surface, the evidence supports this concept. For example, when O2 delivery is diminished, either by the withdrawal of erythrocytes or by the imposition of hypoxia, the rate of oxygen uptake is nearly always reduced in direct proportion. However, these results do not exclude the alternative interpretation that delivery is merely adequate (rather than limiting). How strong is the evidence supporting this single-step limitation to
O2max?
Arterial oxygen content can be easily manipulated by changing the concentration of inspired oxygen or by the withdrawal or addition of red blood cells to alter hematocrit. In all cases, oxygen delivery varies with arterial oxygen content. In fact, when delivery is reduced by anemia or hypoxia, the oxygen extraction remains high (90%) and O2max declines in direct proportion to O2 delivery (Lindstedt et al., 1988). However, when delivery is enhanced rather than reduced, a very different pattern emerges. A meticulous study (Spriet et al., 1986) measured arterial oxygen content, cardiac output and
O2max in very highly trained endurance runners (mean
O2max 77.5mlO2kg-1min-1) given up to three units (500ml each) of additional blood. They reported that a large increase in O2 delivery (up to 30%) was accompanied by a slight increase (<7%) in
O2max. As a consequence, O2 extraction dropped from over 90% to under 75% (Fig.3). The simple interpretation of these data is that oxygen delivery exceeded the capacity of the oxygen sink (mitochondria) in the exercising muscles and, hence, that muscle power output was unable to profit from the available oxygen.
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Taken together, these data demonstrate using three different model systems that O2 does track O2 delivery, but only when delivery is reduced not when delivery is supplemented. This suggests to us that delivery is apparently rarely excessive. However, the fact that
O2 does increase somewhat in response to increased O2 delivery also argues against some other single rate-limiting step in the cascade. In other words, just as we see a structural balance accompanying the greatly varying
O2 among mammals, so too within humans there is more evidence for a balance of structures and shared limitation than there is for a single-step limitation. When delivery is enhanced, unless there is a concomitant increase in the aerobic capacity of the muscles, little gain in
O2max is realized.
Are there general rules that apply to human endurance performance?
By expanding our comparisons from within humans to among all mammals, there is a huge ratio of signal to noise such that O2max varies by many orders of magnitude, not just a few per cent. What emerges is a consistent pattern of oxygen balance structures ensuring supply are adequate to supply and utilize the oxygen required to meet the locomotor costs. Furthermore, those structures with the greatest plasticity will vary in proportion to oxygen uptake. These structures seem to be muscle mitochondrial volume and capillary density, cardiac output and hemoglobin concentration. In contrast, structures lacking plasticity (trachea, lungs) must be built with sufficient capacity to accommodate use-induced increases in oxygen demand during an animals lifetime. There is no consistent evidence for a single rate-limiting step across the 5000-fold range of
O2 among mammals, including humans. Finally,
O2max is just one of many interacting factors that collectively conspire to set the upper limits of human endurance performance.
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Acknowledgments |
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