Jose A. L. Calbet

Reductions in Systemic and Skeletal Muscle Blood Flow and Oxygen Delivery Limit Maximal Aerobic Capacity in Humans

Background—A classic, unresolved physiological question is whether central cardiorespiratory and/or local skeletal muscle circulatory factors limit maximal aerobic capacity (&OV0312;o2max) in humans. Severe heat stress drastically reduces &OV0312;o2max, but the mechanisms have never been studied. Methods and Results—To determine the main contributing factor that limits &OV0312;o2max 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°C and +1°C). Heat stress reduced &OV0312;o2max, 2-legged &OV0312;o2, 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 &OV0312;o2 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 &OV0312;o2max 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.

Exercise and Bone Mass in Adults

There is a substantial body of evidence indicating that exercise prior to the pubertal growth spurt stimulates bone growth and skeletal muscle hypertrophy to a greater degree than observed during growth in non-physically active children. Bone mass can be increased by some exercise programmes in adults and the elderly, and attenuate the losses in bone mass associated with aging. This review provides an overview of cross-sectional and longitudinal studies performed to date involving training and bone measurements. Cross-sectional studies show in general that exercise modalities requiring high forces and/or generating high impacts have the greatest osteogenic potential. Several training methods have been used to improve bone mineral density (BMD) and content in prospective studies. Not all exercise modalities have shown positive effects on bone mass. For example, unloaded exercise such as swimming has no impact on bone mass, while walking or running has limited positive effects.It is not clear which training method is superior for bone stimulation in adults, although scientific evidence points to a combination of high-impact (i.e. jumping) and weight-lifting exercises. Exercise involving high impacts, even a relatively small amount, appears to be the most efficient for enhancing bone mass, except in postmenopausal women. Several types of resistance exercise have been tested also with positive results, especially when the intensity of the exercise is high and the speed of movement elevated. A handful of other studies have reported little or no effect on bone density. However, these results may be partially attributable to the study design, intensity and duration of the exercise protocol, and the bone density measurement techniques used. Studies performed in older adults show only mild increases, maintenance or just attenuation of BMD losses in postmenopausal women, but net changes in BMD relative to control subjects who are losing bone mass are beneficial in decreasing fracture risk. Older men have been less studied than women, and although it seems that men may respond better than their female counterparts, the experimental evidence for a dimorphism based on sex in the osteogenic response to exercise in the elderly is weak. A randomized longitudinal study of the effects of exercise on bone mass in elderly men and women is still lacking. It remains to be determined if elderly females need a different exercise protocol compared with men of similar age. Impact and resistance exercise should be advocated for the prevention of osteoporosis. For those with osteoporosis, weight-bearing exercise in general, and resistance exercise in particular, as tolerated, along with exercise targeted to improve balance, mobility and posture, should be recommended to reduce the likelihood of falling and its associated morbidity and mortality. Additional randomized controlled trials are needed to determine the most efficient training loads depending on age, sex, current bone mass and training history for improvement of bone mass.

Role of caloric content on gastric emptying in humans.

1. This study examined the effects of caloric content (caloric density and the nature of calories) on the rate of gastric emptying using the double‐sampling gastric aspiration technique. Four test meals of 600 ml (glucose, 0.1 kcal ml‐1; pea and whey peptide hydrolysates, both 0.2 kcal ml‐1; milk protein, 0.7 kcal ml‐1) were tested in six healthy subjects in random order on four separate occasions. 2. The glucose solution was emptied the fastest with a half‐time of 9.4 +/‐ 1.2 min (P < 0.05) and the milk protein the slowest with a half‐time of 26.4 +/‐ 10.0 min (P < 0.05); the pea peptide hydrolysate and whey peptide hydrolysate solutions had half‐times of emptying of 16.3 +/‐ 5.4 and 17.2 +/‐ 6.1 min, respectively. The rates of gastric emptying for the peptide hydrolysate solutions derived from different protein sources were not different. 3. Despite the lower rate of gastric emptying for the milk protein solution, the rate of caloric delivery to the duodenum during the early phase of the gastric emptying process was higher than that for the other three solutions (46.3 +/‐ 6, 63.5 +/‐ 22, 62.5 +/‐ 19 and 113.8 +/‐ 25 cal min‐1 kg‐1 for the glucose, pea peptide hydrolysate, whey peptide hydrolysate and milk protein meals, respectively; P < 0.05). The caloric density of the test solutions was linearly related to the half‐time of gastric emptying (r = 0.96, P < 0.05) as well as to the rate at which calories were delivered to the duodenum (r = 0.99, P < 0.001). 4. This study demonstrates that the rate of gastric emptying is a function of the caloric density of the ingested meal and that a linear relationship exists between these variables. Furthermore, the nature of the calories seems to play a minor role in determining the rate of gastric emptying in humans.

Point: In health and in a normoxic environment, V̇o2 max is limited primarily by cardiac output and locomotor muscle blood flow

Starting in the 1950s, a number of experiments provided the experimental evidence supporting the original concept elaborated on by Hill and Lupton ([12][1]): in health, Vo2 max in normoxia is limited primarily by cardiac output and locomotor muscle blood flow ([17][2]). The main variable

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

A universal O2 sensor presumes that compensation for impaired O2delivery is triggered by low O2tension, but in humans, comparisons of compensatory responses to altered arterial O2 content ([Formula: see text]) or tension ([Formula: see text]) have not been reported. To directly compare cardiac output (Q˙TOT) and leg blood flow (LBF) responses to a range of[Formula: see text] and[Formula: see text], 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[Formula: see text] of 0.21 or 0.11. The interventions resulted in two conditions with matched[Formula: see text] but markedly different [Formula: see text] (hypoxia and anemia) and two conditions with matched[Formula: see text] and different[Formula: see text] (hypoxia and anemia + hypoxia). [Formula: see text] 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[Formula: see text] dropped from 190 ± 5 ml/l in control to 132 ± 2 ml/l in anemia + hypoxia ( P < 0.001),Q˙TOT 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 ofQ˙TOT, LBF, and arterial O2 delivery to contracting intact human skeletal muscle is dependent for signaling primarily on[Formula: see text], not[Formula: see text]. This finding suggests that factors related to [Formula: see text]or [Hb] may play an important role in the regulation of blood flow during exercise in humans.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.

Chronic hypoxia increases blood pressure and noradrenaline spillover in healthy humans

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 (× 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.

Cycling efficiency and pedalling frequency in road cyclists.

Abstract The purpose of this study was to determine the influence of pedalling rate on cycling efficiency in road cyclists. Seven competitive road cyclists participated in the study. Four separate experimental sessions were used to determine oxygen uptake (V˙O2) and carbon dioxide output (V˙CO2) at six exercise intensities that elicited a V˙O2 equivalent to 54, 63, 73, 80, 87 and 93% of maximum V˙O2 (V˙O2max). Exercise intensities were administered in random order, separated by rest periods of 3–5 min; four pedalling frequencies (60, 80, 100 and 120 rpm) were randomly tested per intensity. The oxygen cost of cycling was always lower when the exercise was performed at 60 rpm. At each exercise intensity, V˙O2 showed a parabolic dependence on pedalling rate (r = 0.99–1, all P < 0.01) with a curvature that flattened as intensity increased. Likewise, the relationship between power output and gross efficiency (GE) was also best fitted to a parabola (r = 0.94–1, all P < 0.05). Regardless of pedalling rate, GE improved with increasing exercise intensity (P < 0.001). Conversely, GE worsened with pedalling rate (P < 0.001). Interestingly, the effect of pedalling cadence on GE decreased as a linear function of power output (r = 0.98, n = 6, P < 0.001). Similar delta efficiency (DE) values were obtained regardless of pedalling rate [21.5 (0.8), 22.3 (1.2), 22.6 (0.6) and 23.9 (1.0)%, for the 60, 80, 100 and 120 rpm, mean (SEM) respectively]. However, in contrast to GE, DE increased as a linear function of pedalling rate (r = 0.98, P < 0.05). The rate at which pulmonary ventilation increased was accentuated for the highest pedalling rate (P < 0.05), even after accounting for differences in exercise intensity and V˙O2 (P < 0.05). Pedalling rate per se did not have any influence on heart rate which, in turn, increased linearly with V˙O2. These results may help us to understand why competitive cyclists often pedal at cadences of 90–105 rpm to sustain a high power output during prolonged exercise.

Regular participation in sports is associated with enhanced physical fitness and lower fat mass in prepubertal boys

OBJECTIVE: To study the effect of physical activity on whole body fat (BF), its regional deposition and the influence of body fatness on physical performance in prepubertal children.DESSIGN: Cross-sectional study.SUBJECTS: A total of 114 boys (9.4±1.5 y, Tanner I–II), randomly sampled from the population of Gran Canaria (Spain), 63 of them physically active (PA, at least 3 h per week during the previous year) and 51 nonphysically active (non-PA).MEASUREMENTS: Body composition (DXA), anthropometric variables (body circumferences and skinfolds) and physical fitness were determined in all subjects.RESULTS: The PA obtained better results in maximal oxygen uptake, isometric leg extension force, vertical jump (muscular power), and 300 m (anaerobic capacity) and 30 m running tests (speed) than the non-PA. A lower percentage of body fat (% BF) (4 U less, P<0.05), whole BF mass (36% less, P<0.05) and regional fat mass (28, 25, and 30% less in the trunk, legs and arms, respectively, all P<0.05) was observed in the PA compared to the non-PA. The waist and hip circumferences correlated more closely with both the fat mass accumulated in the trunk region and the % BF (r=0.81–0.95, P<0.001) than the waist-to-hip ratio (WHR). The WHR correlated with the percentage of the whole fat mass accumulated in the trunk (PFT) (r=0.52–0.53, P<0.001). In both groups, the PFT increased curvilinearly with the % BF, regardless of the level of physical activity. ANCOVA analysis revealed that total and regional fat masses explained less than 40% of the difference in performance between the PA and non-PA group. The mean speed in the 30 m running test (V30), combined with the height and whole body mass, has predictive value for the BF mass (R=0.98, P<0.001). The % BF may be estimated from the body mass index (BMI) and V30 (% BF=8.09+2.44·BMI (kg m−2)–5.8·V30 (m s−1), R=0.94, P<0.001) in prepubertal boys.CONCLUSIONS: Regular participation in at least 3 h per week of sports activities and competitions on top of the compulsory physical education program is associated with increased physical fitness, lower whole body and trunkal fat mass in prepubertal boys.

Maximal muscular vascular conductances during whole body upright exercise in humans

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 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 ∼76% of and at 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) (∼87 mmHg), systemic VC, systemic oxygen delivery and pulmonary (∼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 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.

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

The purpose of this investigation was to determine the contribution of muscle O2 consumption () to pulmonary O2 uptake () 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 (direct Fick technique) and (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 and were modelled using non‐linear regression. The time constant (τ) describing the phase II kinetics following the onset of exercise was not significantly different from the mean response time (initial time delay +τ) for 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 ∼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 kinetics reflect kinetics during exercise but not during recovery where caution in data interpretation is advised. Increased probably makes a small contribution to during the first 15–20 s of exercise.