Cardiac output and leg and arm blood flow during incremental exercise to exhaustion on the cycle ergometer

[EN] To determine central and peripheral hemodynamic responses to upright leg cycling exercise, nine physically active men underwent measurements of arterial blood pressure and gases, as well as femoral and subclavian vein blood flows and gases during incremental exercise to exhaustion (Wmax). Cardiac output (CO) and leg blood flow (BF) increased in parallel with exercise intensity. In contrast, arm BF remained at 0.8 l/min during submaximal exercise, increasing to 1.2 +/- 0.2 l/min at maximal exercise (P < 0.05) when arm O(2) extraction reached 73 +/- 3%. The leg received a greater percentage of the CO with exercise intensity, reaching a value close to 70% at 64% of Wmax, which was maintained until exhaustion. The percentage of CO perfusing the trunk decreased with exercise intensity to 21% at Wmax, i.e., to approximately 5.5 l/min. For a given local Vo(2), leg vascular conductance (VC) was five- to sixfold higher than arm VC, despite marked hemoglobin deoxygenation in the subclavian vein. At peak exercise, arm VC was not significantly different than at rest. Leg Vo(2) represented approximately 84% of the whole body Vo(2) at intensities ranging from 38 to 100% of Wmax. Arm Vo(2) contributed between 7 and 10% to the whole body Vo(2). From 20 to 100% of Wmax, the trunk Vo(2) (including the gluteus muscles) represented between 14 and 15% of the whole body Vo(2). In summary, vasoconstrictor signals efficiently oppose the vasodilatory metabolites in the arms, suggesting that during whole body exercise in the upright position blood flow is differentially regulated in the upper and lower extremities.

Chronic hypoxia increases blood pressure and noradrenaline spillover in healthy humans

[EN] Chronic hypoxia is associated with elevated sympathetic activity and hypertension in patients with chronic pulmonary obstructive disease. However, the effect of chronic hypoxia on systemic and regional sympathetic activity in healthy humans remains unknown. To determine if chronic hypoxia in healthy humans is associated with hyperactivity of the sympathetic system, we measured intra-arterial blood pressure, arterial blood gases, systemic and skeletal muscle noradrenaline (norepinephrine) spillover and vascular conductances in nine Danish lowlanders at sea level and after 9 weeks of exposure at 5260 m. Mean blood pressure was 28 % higher at altitude (P < 0.01) due to increases in both systolic (18 % higher, P < 0.05) and diastolic (41 % higher, P < 0.001) blood pressures. Cardiac output and leg blood flow were not altered by chronic hypoxia, but systemic vascular conductance was reduced by 30 % (P < 0.05). Plasma arterial noradrenaline (NA) and adrenaline concentrations were 3.7- and 2.4-fold higher at altitude, respectively (P < 0.05). The elevation of plasma arterial NA concentration was caused by a 3.8-fold higher whole-body NA release (P < 0.001) since whole-body noradrenaline clearance was similar in both conditions. Leg NA spillover was increased similarly (x 3.2, P < 0.05). These changes occurred despite the fact that systemic O2 delivery was greater after altitude acclimatisation than at sea level, due to 37 % higher blood haemoglobin concentration. In summary, this study shows that chronic hypoxia causes marked activation of the sympathetic nervous system in healthy humans and increased systemic arterial pressure, despite normalisation of the arterial O2 content with acclimatisation.

On the mechanisms that limit oxygen uptake during exercise in acute and chronic hypoxia: role of muscle mass

[EN] Peak aerobic power in humans (VO2,peak) is markedly affected by inspired O2 tension (FIO2). The question to be answered in this study is what factor plays a major role in the limitation of muscle peak VO2 in hypoxia: arterial O2 partial pressure (Pa,O2) or O2 content (Ca,O2)? Thus, cardiac output (dye dilution with Cardio-green), leg blood flow (thermodilution), intra-arterial blood pressure and femoral arterial-to-venous differences in blood gases were determined in nine lowlanders studied during incremental exercise using a large (two-legged cycle ergometer exercise: Bike) and a small (one-legged knee extension exercise: Knee)muscle mass in normoxia, acute hypoxia (AH) (FIO2 = 0.105) and after 9 weeks of residence at 5260 m (CH). Reducing the size of the active muscle mass blunted by 62% the effect of hypoxia on VO2,peak in AH and abolished completely the effect of hypoxia on VO2,peak after altitude acclimatization. Acclimatization improved Bike peak exercise Pa,O2 from 34 +/- 1 in AH to 45 +/- 1 mmHg in CH(P <0.05) and Knee Pa,O2 from 38 +/- 1 to 55 +/- 2 mmHg(P <0.05). Peak cardiac output and leg blood flow were reduced in hypoxia only during Bike. Acute hypoxia resulted in reduction of systemic O2 delivery (46 and 21%) and leg O2 delivery (47 and 26%) during Bike and Knee, respectively, almost matching the corresponding reduction in VO2,peak. Altitude acclimatization restored fully peak systemic and leg O(2) delivery in CH (2.69 +/- 0.27 and 1.28 +/- 0.11 l min(-1), respectively) to sea level values (2.65 +/- 0.15 and 1.16 +/- 0.11 l min(-1), respectively) during Knee, but not during Bike. During Knee in CH, leg oxygen delivery was similar to normoxia and, therefore, also VO2,peak in spite of a Pa,O2 of 55 mmHg. Reducing the size of the active mass improves pulmonary gas exchange during hypoxic exercise, attenuates the Bohr effect on oxygen uploading at the lungs and preserves sea level convective O2 transport to the active muscles. Thus, the altitude-acclimatized human has potentially a similar exercising capacity as at sea level when the exercise model allows for an adequate oxygen delivery (blood flow x Ca,O2), with only a minor role of Pa,O2 per se, when Pa,O2 is more than 55 mmHg.

Maximal muscular vascular conductances during whole body upright exercise in humans

[EN] That muscular blood flow may reach 2.5 l kg(-1) min(-1) in the quadriceps muscle has led to the suggestion that muscular vascular conductance must be restrained during whole body exercise to avoid hypotension. The main aim of this study was to determine the maximal arm and leg muscle vascular conductances (VC) during leg and arm exercise, to find out if the maximal muscular vasodilatory response is restrained during maximal combined arm and leg exercise. Six Swedish elite cross-country skiers, age (mean +/-s.e.m.) 24 +/- 2 years, height 180 +/- 2 cm, weight 74 +/- 2 kg, and maximal oxygen uptake (VO(2,max)) 5.1 +/- 0.1 l min(-1) participated in the study. Femoral and subclavian vein blood flows, intra-arterial blood pressure, cardiac output, as well as blood gases in the femoral and subclavian vein, right atrium and femoral artery were determined during skiing (roller skis) at approximately 76% of VO(2,max) and at VO(2,max) with different techniques: diagonal stride (combined arm and leg exercise), double poling (predominantly arm exercise) and leg skiing (predominantly leg exercise). During submaximal exercise cardiac output (26-27 l min(-1)), mean blood pressure (MAP) (approximately 87 mmHg), systemic VC, systemic oxygen delivery and pulmonary VO2(approximately 4 l min(-1)) attained similar values regardless of exercise mode. The distribution of cardiac output was modified depending on the musculature engaged in the exercise. There was a close relationship between VC and VO2 in arms (r= 0.99, P < 0.001) and legs (r= 0.98, P < 0.05). Peak arm VC (63.7 +/- 5.6 ml min(-1) mmHg(-1)) was attained during double poling, while peak leg VC was reached at maximal exercise with the diagonal technique (109.8 +/- 11.5 ml min(-1) mmHg(-1)) when arm VC was 38.8 +/- 5.7 ml min(-1) mmHg(-1). If during maximal exercise arms and legs had been vasodilated to the observed maximal levels then mean arterial pressure would have dropped at least to 75-77 mmHg in our experimental conditions. It is concluded that skeletal muscle vascular conductance is restrained during whole body exercise in the upright position to avoid hypotension.

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.

The ergogenic effect of recombinant human erythropoietin on VO2max depends on the severity of arterial hypoxemia

Treatment with recombinant human erythropoietin (rhEpo) induces a rise in blood oxygen-carrying capacity (CaO(2)) that unequivocally enhances maximal oxygen uptake (VO(2)max) during exercise in normoxia, but not when exercise is carried out in severe acute hypoxia. This implies that there should be a threshold altitude at which VO(2)max is less dependent on CaO(2). To ascertain which are the mechanisms explaining the interactions between hypoxia, CaO(2) and VO(2)max we measured systemic and leg O(2) transport and utilization during incremental exercise to exhaustion in normoxia and with different degrees of acute hypoxia in eight rhEpo-treated subjects. Following prolonged rhEpo treatment, the gain in systemic VO(2)max observed in normoxia (6-7%) persisted during mild hypoxia (8% at inspired O(2) fraction (F(I)O(2)) of 0.173) and was even larger during moderate hypoxia (14-17% at F(I)O(2) = 0.153-0.134). When hypoxia was further augmented to F(I)O(2) = 0.115, there was no rhEpo-induced enhancement of systemic VO(2)max or peak leg VO(2). The mechanism highlighted by our data is that besides its strong influence on CaO(2), rhEpo was found to enhance leg VO(2)max in normoxia through a preferential redistribution of cardiac output toward the exercising legs, whereas this advantageous effect disappeared during severe hypoxia, leaving augmented CaO(2) alone insufficient for improving peak leg O(2) delivery and VO(2). Finally, that VO(2)max was largely dependent on CaO(2) during moderate hypoxia but became abruptly CaO(2)-independent by slightly increasing the severity of hypoxia could be an indirect evidence of the appearance of central fatigue.

Reductions in systemic and skeletal muscle blood flow and oxygen delivery limit maximal aerobic capacity in humans

[EN] BACKGROUND: A classic, unresolved physiological question is whether central cardiorespiratory and/or local skeletal muscle circulatory factors limit maximal aerobic capacity (VO2max) in humans. Severe heat stress drastically reduces VO2max, but the mechanisms have never been studied. METHODS AND RESULTS: To determine the main contributing factor that limits VO2max with and without heat stress, we measured hemodynamics in 8 healthy males performing intense upright cycling exercise until exhaustion starting with either high or normal skin and core temperatures (+10 degrees C and +1 degrees C). Heat stress reduced VO2max, 2-legged VO2, and time to fatigue by 0.4+/-0.1 L/min (8%), 0.5+/-0.2 L/min (11%), and 2.2+/-0.4 minutes (28%), respectively (all P<0.05), despite heart rate and core temperature reaching similar peak values. However, before exhaustion in both heat stress and normal conditions, cardiac output, leg blood flow, mean arterial pressure, and systemic and leg O2 delivery declined significantly (all 5% to 11%, P<0.05), yet arterial O2 content and leg vascular conductance remained unchanged. Despite increasing leg O2 extraction, leg VO2 declined 5% to 6% before exhaustion in both heat stress and normal conditions, accompanied by enhanced muscle lactate accumulation and ATP and creatine phosphate hydrolysis. CONCLUSIONS: These results demonstrate that in trained humans, severe heat stress reduces VO2max by accelerating the declines in cardiac output and mean arterial pressure that lead to decrements in exercising muscle blood flow, O2 delivery, and O2 uptake. Furthermore, the impaired systemic and skeletal muscle aerobic capacity that precedes fatigue with or without heat stress is largely related to the failure of the heart to maintain cardiac output and O2 delivery to locomotive muscle.

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.

The re-establishment of the normal blood lactate response to exercise in humans after prolonged acclimatization to altitude

[EN] 1. One to five weeks of chronic exposure to hypoxia has been shown to reduce peak blood lactate concentration compared to acute exposure to hypoxia during exercise, the high altitude 'lactate paradox'. However, we hypothesize that a sufficiently long exposure to hypoxia would result in a blood lactate and net lactate release from the active leg to an extent similar to that observed in acute hypoxia, independent of work intensity. 2. Six Danish lowlanders (25-26 years) were studied during graded incremental bicycle exercise under four conditions: at sea level breathing either ambient air (0 m normoxia) or a low-oxygen gas mixture (10 % O(2) in N(2), 0 m acute hypoxia) and after 9 weeks of acclimatization to 5260 m breathing either ambient air (5260 m chronic hypoxia) or a normoxic gas mixture (47 % O(2) in N(2), 5260 m acute normoxia). In addition, one-leg knee-extensor exercise was performed during 5260 m chronic hypoxia and 5260 m acute normoxia. 3. During incremental bicycle exercise, the arterial lactate concentrations were similar at sub-maximal work at 0 m acute hypoxia and 5260 m chronic hypoxia but higher compared to both 0 m normoxia and 5260 m acute normoxia. However, peak lactate concentration was similar under all conditions (10.0 +/- 1.3, 10.7 +/- 2.0, 10.9 +/- 2.3 and 11.0 +/- 1.0 mmol l(-1)) at 0 m normoxia, 0 m acute hypoxia, 5260 m chronic hypoxia and 5260 m acute normoxia, respectively. Despite a similar lactate concentration at sub-maximal and maximal workload, the net lactate release from the leg was lower during 0 m acute hypoxia (peak 8.4 +/- 1.6 mmol min(-1)) than at 5260 m chronic hypoxia (peak 12.8 +/- 2.2 mmol min(-1)). The same was observed for 0 m normoxia (peak 8.9 +/- 2.0 mmol min(-1)) compared to 5260 m acute normoxia (peak 12.6 +/- 3.6 mmol min(-1)). Exercise after acclimatization with a small muscle mass (one-leg knee-extensor) elicited similar lactate concentrations (peak 4.4 +/- 0.2 vs. 3.9 +/- 0.3 mmol l(-1)) and net lactate release (peak 16.4 +/- 1.8 vs. 14.3 mmol l(-1)) from the active leg at 5260 m chronic hypoxia and 5260 m acute normoxia. 4. In conclusion, in lowlanders acclimatized for 9 weeks to an altitude of 5260 m, the arterial lactate concentration was similar at 0 m acute hypoxia and 5260 m chronic hypoxia. The net lactate release from the active leg was higher at 5260 m chronic hypoxia compared to 0 m acute hypoxia, implying an enhanced lactate utilization with prolonged acclimatization to altitude. The present study clearly shows the absence of a lactate paradox in lowlanders sufficiently acclimatized to altitude.

Muscle blood flow is reduced with dehydration during prolonged exercise in humans

[EN] 1. The present study examined whether the blood flow to exercising muscles becomes reduced when cardiac output and systemic vascular conductance decline with dehydration during prolonged exercise in the heat. A secondary aim was to determine whether the upward drift in oxygen consumption (VO2) during prolonged exercise is confined to the active muscles. 2. Seven euhydrated, endurance-trained cyclists performed two bicycle exercise trials in the heat (35 C; 40-50 % relative humidity; 61 +/- 2 % of maximal VO2), separated by 1 week. During the first trial (dehydration trial, DE), they bicycled until volitional exhaustion (135 +/- 4 min, mean +/- s.e.m.), while developing progressive dehydration and hyperthermia (3.9 +/- 0.3 % body weight loss; 39.7 +/- 0.2 C oesophageal temperature, Toes). In the second trial (control trial), they bicycled for the same period of time while maintaining euhydration by ingesting fluids and stabilizing Toes at 38.2 +/- 0.1 C after 30 min exercise. 3. In both trials, cardiac output, leg blood flow (LBF), vascular conductance and VO2 were similar after 20 min exercise. During the 20 min-exhaustion period of DE, cardiac output, LBF and systemic vascular conductance declined significantly (8-14 %; P < 0.05) yet muscle vascular conductance was unaltered. In contrast, during the same period of control, all these cardiovascular variables tended to increase. After 135 +/- 4 min of DE, the 2.0 +/- 0.6 l min-1 lower blood flow to the exercising legs accounted for approximately two-thirds of the reduction in cardiac output. Blood flow to the skin also declined markedly as forearm blood flow was 39 +/- 8 % (P < 0.05) lower in DE vs. control after 135 +/- 4 min. 4. In both trials, whole body VO2 and leg VO2 increased in parallel and were similar throughout exercise. The reduced leg blood flow in DE was accompanied by an even greater increase in femoral arterial-venous O2 (a-vO2) difference. 5. It is concluded that blood flow to the exercising muscles declines significantly with dehydration, due to a lowering in perfusion pressure and systemic blood flow rather than increased vasoconstriction. Furthermore, the progressive increase in oxygen consumption during exercise is confined to the exercising skeletal muscles.