Maximal O2 Transport Research Articles

Effects of lung ventilation-perfusion and muscle metabolism-perfusion heterogeneities on maximal O2 transport and utilization.

We expanded a prior model of whole-body O2 transport and utilization based on diffusive O2 exchange in the lungs and tissues to additionally allow for both lung ventilation-perfusion and tissue metabolism-perfusion heterogeneities, in order to estimate V̇O2 and mitochondrial PO2 (PmO2) during maximal exercise. Simulations were performed using data from (a) healthy fit subjects exercising at sea level and at altitudes up to the equivalent of Mount Everest and (b) patients with mild and severe chronic obstructive pulmonary disease (COPD) exercising at sea level. Heterogeneity in skeletal muscle may affect maximal O2 availability more than heterogeneity in lung, especially if mitochondrial metabolic capacity (V̇ MAX ) is only slightly higher than the potential to deliver O2 , but when V̇ MAX is substantially higher than O2 delivery, the effect of muscle heterogeneity is comparable to that of lung heterogeneity. Skeletal muscle heterogeneity may result in a wide range of potential mitochondrial PO 2 values, a range that becomes narrower as V̇ MAX increases; in regions with a low ratio of metabolic capacity to blood flow, PmO2 can exceed that of mixed muscle venous blood. The combined effects of lung and peripheral heterogeneities on the resistance to O2 flow in health decreases with altitude. Previous models of O2 transport and utilization in health considered diffusive exchange of O2 in lung and muscle, but, reasonably, neglected functional heterogeneities in these tissues. However, in disease, disregarding such heterogeneities would not be justified. Here, pulmonary ventilation-perfusion and skeletal muscle metabolism-perfusion mismatching were added to a prior model of only diffusive exchange. Previously ignored O2 exchange in non-exercising tissues was also included. We simulated maximal exercise in (a) healthy subjects at sea level and altitude, and (b) COPD patients at sea level, to assess the separate and combined effects of pulmonary and peripheral functional heterogeneities on overall muscle O2 uptake (V̇O2) and on mitochondrial PO2 (PmO2). In healthy subjects at maximal exercise, the combined effects of pulmonary and peripheral heterogeneities reduced arterial PO2 (PaO2) at sea level by 32mmHg, but muscle V̇O2 by only 122mlmin(-1) (-3.5%). At the altitude of Mt Everest, lung and tissue heterogeneity together reduced PaO2 by less than 1mmHg and V̇O2 by 32mlmin(-1) (-2.4%). Skeletal muscle heterogeneity led to a wide range of potential PmO2 among muscle regions, a range that becomes narrower asV̇ MAX increases, and in regions with a low ratio of metabolic capacity to blood flow, PmO2 can exceed that of mixed muscle venous blood. For patients with severe COPD, peak V̇O2 was insensitive to substantial changes in the mitochondrial characteristics for O2 consumption or the extent of muscle heterogeneity. This integrative computational model of O2 transport and utilization offers the potential for estimating profiles of PmO2 both in health and in diseases such as COPD if the extent for both lung ventilation-perfusion and tissue metabolism-perfusion heterogeneity is known.

Importance of mitochondrial [formula omitted] in maximal O2 transport and utilization: A theoretical analysis

In previous calculations of how the O2 transport system limits V˙O2max, it was reasonably assumed that mitochondrial PO2 (PmO2) could be neglected (set to zero). However, in reality, PmO2 must exceed zero and the red cell to mitochondrion diffusion gradient may therefore be reduced, impairing diffusive transport of O2 and V˙O2max. Accordingly, we investigated the influence of PmO2 on these calculations by coupling previously used equations for O2 transport to one for mitochondrial respiration relating mitochondrial V˙O2 to PO2. This hyperbolic function, characterized by its P50 and V˙MAX, allowed PmO2 to become a model output (rather than set to zero as previously). Simulations using data from exercising normal subjects showed that at V˙O2max, PmO2 was usually <1mmHg, and that the effects on V˙O2max were minimal. However, when O2 transport capacity exceeded mitochondrial V˙MAX, or if P50 were elevated, PmO2 often reached double digit values, thereby reducing the diffusion gradient and significantly decreasing V˙O2max.

Determinant factors of the decrease in aerobic performance in moderate acute hypoxia in women endurance athletes

The purpose of this study was to evaluate the limiting factors of maximal aerobic performance in endurance trained (TW) and sedentary (UW) women. Subjects performed four incremental tests on a cycle ergometer at sea level and in normobaric hypoxia corresponding to 1000, 2500 and 4500 m. Maximal oxygen uptake decrement (Delta VO2 max) was larger in TW at each altitude. Maximal heart rate and ventilation decreased at 4500 m in TW. Maximal cardiac output remained unchanged. In both groups, arterialized oxygen saturation (Sa'O2 max) decreased at and above 2500 m and maximal O2 transport (QaO2 max) decreased from 1000 m. At 4500 m, there was no more difference in QaO2 max between TW and UW. Mixed venous O2 pressure (PvO2 max) was lower and O2 extraction (O2ERmax) greater in TW at each altitude. The primary determinant factor of VO2 max decrement in moderate acute hypoxia in trained and untrained women is a reduced maximal O2 transport that cannot be compensate by tissue O2 extraction.

Living high–training low: effect on erythropoiesis and maximal aerobic performance in elite Nordic skiers

The "living high-training low" model (Hi-Lo) may improve aerobic performance in athletes, and the main mechanism of this improvement is thought to be augmented erythropoiesis. A positive effect of Hi-Lo has been demonstrated previously by using altitudes of 2,000-3,000 m. Since the rate of erythropoiesis is altitude-dependent, we tested whether a higher altitude (3,500 m) during Hi-Lo increases erythropoiesis and maximal aerobic performance. Nordic skiers trained for 18 days at 1,200 m, while sleeping at 1,200 m in ambient air (control group, n = 5) or in hypoxic rooms (Hi-Lo, n = 6; 3 x 6 days at simulated altitudes of 2,500, 3,000 and finally 3,500 m, 11 h day(-1)). Measurements were done before, during (blood samples only) and 2 weeks after the intervention (POST). Maximal aerobic performance was examined from VO(2max) and time to exhaustion (T(exh)) at vVO(2max) (minimum speed associated with VO(2max)), respectively. Erythropoietin and soluble transferrin receptor responses were higher during Hi-Lo, whereas reticulocytes did not change. In POST (vs. before): hematological parameters were similar to basal levels, as well as red blood cell volume, being 2.68 +/- 0.83 l (vs. 2.64+/-0.54 l) in Hi-Lo and 2.62+/-0.57 l (vs. 2.87 +/- 0.59 l) in controls. At that time, neither VO(2max) nor T(exh) were improved by Hi-Lo, VO(2max) being non-significantly decreased by 2.0% (controls) and 3.7% (Hi-Lo). The present results suggest that increasing the altitude up to 3,500 m during Hi-Lo stimulates erythropoiesis but does not confer any advantage for maximal O2 transport.

Counterpoint: In health and in a normoxic environment, V̇o2 max is not limited primarily by cardiac output and locomotor muscle blood flow

Counterpoint: In health and in a normoxic environment, V̇<scp>o</scp>_{2 max} is not limited primarily by cardiac output and locomotor muscle blood flow

The John Sutton Lecture: CSEP, 2002]. Pulmonary system limitations to exercise in health.

It is commonly held that the structural capacity of the normal lung is "overbuilt" and exceeds the demand for pulmonary O2 and CO2 transport in the healthy, exercising human. On the other hand, the adaptability of pulmonary system structures to habitual physical training is substantially less than are other links in the O2 transport system. Accordingly, in some highly fit, and even in some not so fit habitually active individuals, the lung's diffusion surface, airways, and/or chest-wall musculature are underbuilt relative to the demand for maximal O2 transport. Two specific pulmonary limitations to exercise performance are proposed: (1) exercise-induced arterial hypoxemia secondary to excessive widening of the alveolar to arterial O2 difference, inadequate hyperventilation, and metabolic acidosis; and (2) highly fatiguing levels of respiratory muscle work which effectively steals blood flow from locomotor muscles via sympathetically mediated reflexes and heightens the perception of limb discomfort and dyspnea. In this brief review, we describe the characteristics and causes of each of these proposed pulmonary limitations and their consequences to maximal O2 uptake and exercise performance.