Effects of ATP-induced leg vasodilation on VO2 peak and leg O2 extraction during maximal exercise in humans

[EN] During maximal whole body exercise VO2 peak is limited by O2 delivery. In turn, it is though that blood flow at near-maximal exercise must be restrained by the sympathetic nervous system to maintain mean arterial pressure. To determine whether enhancing vasodilation across the leg results in higher O2 delivery and leg VO2 during near-maximal and maximal exercise in humans, seven men performed two maximal incremental exercise tests on the cycle ergometer. In random order, one test was performed with and one without (control exercise) infusion of ATP (8 mg in 1 ml of isotonic saline solution) into the right femoral artery at a rate of 80 microg.kg body mass-1.min-1. During near-maximal exercise (92% of VO2 peak), the infusion of ATP increased leg vascular conductance (+43%, P<0.05), leg blood flow (+20%, 1.7 l/min, P<0.05), and leg O2 delivery (+20%, 0.3 l/min, P<0.05). No effects were observed on leg or systemic VO2. Leg O2 fractional extraction was decreased from 85+/-3 (control) to 78+/-4% (ATP) in the infused leg (P<0.05), while it remained unchanged in the left leg (84+/-2 and 83+/-2%; control and ATP; n=3). ATP infusion at maximal exercise increased leg vascular conductance by 17% (P<0.05), while leg blood flow tended to be elevated by 0.8 l/min (P=0.08). However, neither systemic nor leg peak VO2 values where enhanced due to a reduction of O2 extraction from 84+/-4 to 76+/-4%, in the control and ATP conditions, respectively (P<0.05). In summary, the VO2 of the skeletal muscles of the lower extremities is not enhanced by limb vasodilation at near-maximal or maximal exercise in humans. The fact that ATP infusion resulted in a reduction of O2 extraction across the exercising leg suggests a vasodilating effect of ATP on less-active muscle fibers and other noncontracting tissues and that under normal conditions these regions are under high vasoconstrictor influence to ensure the most efficient flow distribution of the available cardiac output to the most active muscle fibers of the exercising limb.

Muscular and pulmonary O2 uptake kinetics during moderate- and high-intensity sub-maximal knee-extensor exercise in humans

[EN] The purpose of this investigation was to determine the contribution of muscle O(2) consumption (mVO2) to pulmonary O(2) uptake (pVO2) during both low-intensity (LI) and high-intensity (HI) knee-extension exercise, and during subsequent recovery, in humans. Seven healthy male subjects (age 20-25 years) completed a series of LI and HI square-wave exercise tests in which mVO2 (direct Fick technique) and pVO2 (indirect calorimetry) were measured simultaneously. The mean blood transit time from the muscle capillaries to the lung (MTTc-l) was also estimated (based on measured blood transit times from femoral artery to vein and vein to artery). The kinetics of mVO2 and pVO2 were modelled using non-linear regression. The time constant (tau) describing the phase II pVO2 kinetics following the onset of exercise was not significantly different from the mean response time (initial time delay + tau) for mVO2 kinetics for LI (30 +/- 3 vs 30 +/- 3 s) but was slightly higher (P < 0.05) for HI (32 +/- 3 vs 29 +/- 4 s); the responses were closely correlated (r = 0.95 and r = 0.95; P < 0.01) for both intensities. In recovery, agreement between the responses was more limited both for LI (36 +/- 4 vs 18 +/- 4 s, P < 0.05; r = -0.01) and HI (33 +/- 3 vs 27 +/- 3 s, P > 0.05; r = -0.40). MTTc-l was approximately 17 s just before exercise and decreased to 12 and 10 s after 5 s of exercise for LI and HI, respectively. These data indicate that the phase II pVO2 kinetics reflect mVO2 kinetics during exercise but not during recovery where caution in data interpretation is advised. Increased mVO2 probably makes a small contribution to during the first 15-20 s of exercise.

Air to muscle O2 delivery during exercise at altitude

[EN] Hypoxia-induced hyperventilation is critical to improve blood oxygenation, particularly when the arterial Po2 lies in the steep region of the O2 dissociation curve of the hemoglobin (ODC). Hyperventilation increases alveolar Po2 and, by increasing pH, left shifts the ODC, increasing arterial saturation (Sao2) 6 to 12 percentage units. Pulmonary gas exchange (PGE) is efficient at rest and, hence, the alveolar-arterial Po2 difference (Pao2-Pao2) remains close to 0 to 5mm Hg. The (Pao2-Pao2) increases with exercise duration and intensity and the level of hypoxia. During exercise in hypoxia, diffusion limitation explains most of the additional Pao2-Pao2. With altitude, acclimatization exercise (Pao2-Pao2) is reduced, but does not reach the low values observed in high altitude natives, who possess an exceptionally high DLo2. Convective O2 transport depends on arterial O2 content (Cao2), cardiac output (Q), and muscle blood flow (LBF). During whole-body exercise in severe acute hypoxia and in chronic hypoxia, peak Q and LBF are blunted, contributing to the limitation of maximal oxygen uptake (Vo2max). During small-muscle exercise in hypoxia, PGE is less perturbed, Cao2 is higher, and peak Q and LBF achieve values similar to normoxia. Although the Po2 gradient driving O2 diffusion into the muscles is reduced in hypoxia, similar levels of muscle O2 diffusion are observed during small-mass exercise in chronic hypoxia and in normoxia, indicating that humans have a functional reserve in muscle O2 diffusing capacity, which is likely utilized during exercise in hypoxia. In summary, hypoxia reduces Vo2max because it limits O2 diffusion in the lung.

Effects of recovery mode on performance, O2 uptake, and O2 deficit during high-intensity intermittent exercise

[EN] The aim of this study was to determine the influence of activity performed during the recovery period on the aerobic and anaerobic energy yield, as well as on performance, during high-intensity intermittent exercise (HIT). Ten physical education students participated in the study. First they underwent an incremental exercise test to assess their maximal power output (Wmax) and VO2max. On subsequent days they performed three different HITs. Each HIT consisted of four cycling bouts until exhaustion at 110% Wmax. Recovery periods of 5 min were allowed between bouts. HITs differed in the kind of activity performed during the recovery periods: pedaling at 20% VO2max (HITA), stretching exercises, or lying supine. Performance was 3-4% and aerobic energy yield was 6-8% (both p < 0.05) higher during the HITA than during the other two kinds of HIT. The greater contribution of aerobic metabolism to the energy yield during the high-intensity exercise bouts with active recovery was due to faster VO2 kinetics (p< 0.01) and a higher VO2peak during the exercise bouts preceded by active recovery (p < 0.05). In contrast, the anaerobic energy yield (oxygen deficit and peak blood lactate concentrations) was similar in all HITs. Therefore, this study shows that active recovery facilitates performance by increasing aerobic contribution to the whole energy yield turnover during high-intensity intermittent exercise.

Effect of blood haemoglobin concentration on V(O2,max) and cardiovascular function in lowlanders acclimatised to 5260 m

[EN] The principal aim of this investigation was to determine the influence of blood haemoglobin concentration ([Hb]) on maximal exercise capacity and maximal O(2) consumption (V(O(2),max)) in healthy subjects acclimatised to high altitude. Secondarily, we examined the effects of [Hb] on the regulation of cardiac output (CO), blood pressure and muscular blood flow (LBF) during exercise. Eight Danish lowlanders (three females and five males; 24 +/- 0.6 years, mean +/- S.E.M.) performed submaximal and maximal exercise on a cycle ergometer after 9 weeks at an altitude of 5260 m (Mt Chacaltaya, Bolivia). This was done first with the high [Hb] resulting from acclimatisation and again 2-4 days later, 1 h after isovolaemic haemodilution with Dextran 70 to near sea level [Hb]. After measurements at maximal exercise while breathing air at each [Hb], subjects were switched to hyperoxia (55 % O(2) in N(2)) and the measurements were repeated, increasing the work rate as tolerated. Hyperoxia increased maximal power output and leg V(O(2),max), showing that breathing ambient air at 5260 m, V(O(2),max) is limited by the availability of O(2) rather than by muscular oxidative capacity. Altitude increased [Hb] by 36 % from 136 +/- 5 to 185 +/- 5 g l(-1) (P < 0.001), while haemodilution (replacing 1 l of blood with 1 l of 6 % Dextran) lowered [Hb] by 24 % to 142 +/- 6 g l(-1) (P < 0.001). Haemodilution had no effect on maximal pulmonary or leg V(O(2),max), or power output. Despite higher LBF, leg O(2) delivery was reduced and maximal V(O(2)) was thus maintained by higher O(2) extraction. While CO increased linearly with work rate irrespective of [Hb] or inspired oxygen fraction (F(I,O(2))), both LBF and leg vascular conductance were systematically higher when [Hb] was low. Close and significant relationships were seen between LBF (and CO) and both plasma noradrenaline and K(+) concentrations, independently of [Hb] and F(I,O(2)). In summary, under conditions where O(2) supply limits maximal exercise, the increase in [Hb] with altitude acclimatisation does not improve maximal exercise capacity or V(O(2),max), and does not alter peak CO. However, LBF and vascular conductance are higher at altitude when [Hb] is lowered to sea level values, with both relating closely to catecholamine and potassium concentrations. This suggests that the lack of effect of [Hb] on V(O(2),max) may involve reciprocal changes in LBF via local metabolic control of the muscle vasculature.

Why is VO2 max after altitude acclimatization still reduced despite normalization of arterial O2 content?

[EN] Acute hypoxia (AH) reduces maximal O2 consumption (VO2 max), but after acclimatization, and despite increases in both hemoglobin concentration and arterial O2 saturation that can normalize arterial O2 concentration ([O2]), VO2 max remains low. To determine why, seven lowlanders were studied at VO2 max (cycle ergometry) at sea level (SL), after 9-10 wk at 5,260 m [chronic hypoxia (CH)], and 6 mo later at SL in AH (FiO2 = 0.105) equivalent to 5,260 m. Pulmonary and leg indexes of O2 transport were measured in each condition. Both cardiac output and leg blood flow were reduced by approximately 15% in both AH and CH (P < 0.05). At maximal exercise, arterial [O2] in AH was 31% lower than at SL (P < 0.05), whereas in CH it was the same as at SL due to both polycythemia and hyperventilation. O2 extraction by the legs, however, remained at SL values in both AH and CH. Although at both SL and in AH, 76% of the cardiac output perfused the legs, in CH the legs received only 67%. Pulmonary VO2 max (4.1 +/- 0.3 l/min at SL) fell to 2.2 +/- 0.1 l/min in AH (P < 0.05) and was only 2.4 +/- 0.2 l/min in CH (P < 0.05). These data suggest that the failure to recover VO2 max after acclimatization despite normalization of arterial [O2] is explained by two circulatory effects of altitude: 1) failure of cardiac output to normalize and 2) preferential redistribution of cardiac output to nonexercising tissues. Oxygen transport from blood to muscle mitochondria, on the other hand, appears unaffected by CH.

Arterial O2 content and tension in regulation of cardiac output and leg blood flow during exercise in humans

[EN] A universal O2 sensor presumes that compensation for impaired O2 delivery is triggered by low O2 tension, but in humans, comparisons of compensatory responses to altered arterial O2 content (CaO2) or tension (PaO2) have not been reported. To directly compare cardiac output (QTOT) and leg blood flow (LBF) responses to a range of CaO2 and PaO2, seven healthy young men were studied during two-legged knee extension exercise with control hemoglobin concentration ([Hb] = 144.4 +/- 4 g/l) and at least 1 wk later after isovolemic hemodilution ([Hb] = 115 +/- 2 g/l). On each study day, subjects exercised twice at 30 W and on to voluntary exhaustion with an FIO2 of 0.21 or 0.11. The interventions resulted in two conditions with matched CaO2 but markedly different PaO2 (hypoxia and anemia) and two conditions with matched PaO2 and different CaO2 (hypoxia and anemia + hypoxia). PaO2 varied from 46 +/- 3 Torr in hypoxia to 95 +/- 3 Torr (range 37 to >100) in anemia (P < 0.001), yet LBF at exercise was nearly identical. However, as CaO2 dropped from 190 +/- 5 ml/l in control to 132 +/- 2 ml/l in anemia + hypoxia (P < 0.001), QTOT and LBF at 30 W rose to 12.8 +/- 0.8 and 7.2 +/- 0.3 l/min, respectively, values 23 and 47% above control (P < 0.01). Thus regulation of QTOT, LBF, and arterial O2 delivery to contracting intact human skeletal muscle is dependent for signaling primarily on CaO2, not PaO2. This finding suggests that factors related to CaO2 or [Hb] may play an important role in the regulation of blood flow during exercise in humans.