José Losa-Reyna

What limits performance during whole-body incremental exercise to exhaustion in humans?

At the end of an incremental exercise to exhaustion a large functional reserve remains in the muscles to generate power, even at levels far above the power output at which task failure occurs, regardless of the inspiratory O2 pressure during the incremental exercise. Exhaustion (task failure) is not due to lactate accumulation and the associated muscle acidification; neither the aerobic energy pathways nor the glycolysis are blocked at exhaustion. Muscle lactate accumulation may actually facilitate early recovery after exhaustive exercise even under ischaemic conditions. Although the maximal rate of ATP provision is markedly reduced at task failure, the resynthesis capacity remaining exceeds the rate of ATP consumption, indicating that task failure during an incremental exercise to exhaustion depends more on central than peripheral mechanisms.

Limitations to oxygen transport and utilization during sprint exercise in humans: evidence for a functional reserve in muscle O2 diffusing capacity

Severe acute hypoxia reduces sprint performance. Muscle V̇O2 during sprint exercise in normoxia is not limited by O2 delivery, O2 offloading from haemoglobin or structure‐dependent diffusion constraints in the skeletal muscle of young healthy men. A large functional reserve in muscle O2 diffusing capacity exists and remains available at exhaustion during exercise in normoxia; this functional reserve is recruited during exercise in hypoxia. During whole‐body incremental exercise to exhaustion in severe hypoxia, leg V̇O2 is primarily dependent on convective O2 delivery and less limited by diffusion constraints than previously thought. The kinetics of O2 offloading from haemoglobin does not limit V̇O2 peak in hypoxia. Our results indicate that the limitation to V̇O2 during short sprints resides in mechanisms regulating mitochondrial respiration.

Task Failure during Exercise to Exhaustion in Normoxia and Hypoxia Is Due to Reduced Muscle Activation Caused by Central Mechanisms While Muscle Metaboreflex Does Not Limit Performance

To determine whether task failure during incremental exercise to exhaustion (IE) is principally due to reduced neural drive and increased metaboreflex activation eleven men (22 ± 2 years) performed a 10 s control isokinetic sprint (IS; 80 rpm) after a short warm-up. This was immediately followed by an IE in normoxia (Nx, PIO2:143 mmHg) and hypoxia (Hyp, PIO2:73 mmHg) in random order, separated by a 120 min resting period. At exhaustion, the circulation of both legs was occluded instantaneously (300 mmHg) during 10 or 60 s to impede recovery and increase metaboreflex activation. This was immediately followed by an IS with open circulation. Electromyographic recordings were obtained from the vastus medialis and lateralis. Muscle biopsies and blood gases were obtained in separate experiments. During the last 10 s of the IE, pulmonary ventilation, VO2, power output and muscle activation were lower in hypoxia than in normoxia, while pedaling rate was similar. Compared to the control sprint, performance (IS-Wpeak) was reduced to a greater extent after the IE-Nx (11% lower P < 0.05) than IE-Hyp. The root mean square (EMGRMS) was reduced by 38 and 27% during IS performed after IE-Nx and IE-Hyp, respectively (Nx vs. Hyp: P < 0.05). Post-ischemia IS-EMGRMS values were higher than during the last 10 s of IE. Sprint exercise mean (IS-MPF) and median (IS-MdPF) power frequencies, and burst duration, were more reduced after IE-Nx than IE-Hyp (P < 0.05). Despite increased muscle lactate accumulation, acidification, and metaboreflex activation from 10 to 60 s of ischemia, IS-Wmean (+23%) and burst duration (+10%) increased, while IS-EMGRMS decreased (−24%, P < 0.05), with IS-MPF and IS-MdPF remaining unchanged. In conclusion, close to task failure, muscle activation is lower in hypoxia than in normoxia. Task failure is predominantly caused by central mechanisms, which recover to great extent within 1 min even when the legs remain ischemic. There is dissociation between the recovery of EMGRMS and performance. The reduction of surface electromyogram MPF, MdPF and burst duration due to fatigue is associated but not caused by muscle acidification and lactate accumulation. Despite metaboreflex stimulation, muscle activation and power output recovers partly in ischemia indicating that metaboreflex activation has a minor impact on sprint performance.

Muscle Activation During Exercise in Severe Acute Hypoxia: Role of Absolute and Relative Intensity

The aim of this study was to determine the influence of severe acute hypoxia on muscle activation during whole body dynamic exercise. Eleven young men performed four incremental cycle ergometer tests to exhaustion breathing normoxic (FIO2=0.21, two tests) or hypoxic gas (FIO2=0.108, two tests). Surface electromyography (EMG) activities of rectus femoris (RF), vastus medialis (VL), vastus lateralis (VL), and biceps femoris (BF) were recorded. The two normoxic and the two hypoxic tests were averaged to reduce EMG variability. Peak VO2 was 34% lower in hypoxia than in normoxia (p<0.05). The EMG root mean square (RMS) increased with exercise intensity in all muscles (p<0.05), with greater effect in hypoxia than in normoxia in the RF and VM (p<0.05), and a similar trend in VL (p=0.10). At the same relative intensity, the RMS was greater in normoxia than in hypoxia in RF, VL, and BF (p<0.05), with a similar trend in VM (p=0.08). Median frequency increased with exercise intensity (p<0.05), and was higher in hypoxia than in normoxia in VL (p<0.05). Muscle contraction burst duration increased with exercise intensity in VM and VL (p<0.05), without clear effects of FIO2. No significant FIO2 effects on frequency domain indices were observed when compared at the same relative intensity. In conclusion, muscle activation during whole body exercise increases almost linearly with exercise intensity, following a muscle-specific pattern, which is adjusted depending on the FIO2 and the relative intensity of exercise. Both VL and VM are increasingly involved in power output generation with the increase of intensity and the reduction in FIO2.

A new equation to estimate temperature-corrected PaCO2 from PET CO2 during exercise in normoxia and hypoxia.

End‐tidal PCO2 (PETCO2) has been used to estimate arterial pressure CO2 (PaCO2). However, the influence of blood temperature on the PaCO2 has not been taken into account. Moreover, there is no equation validated to predict PaCO2 during exercise in severe acute hypoxia. To develop a new equation to predict temperature‐corrected PaCO2 values during exercise in normoxia and severe acute hypoxia, 11 volunteers (21.2 ± 2.1 years) performed incremental exercise to exhaustion in normoxia (Nox, PIO2: 143 mmHg) and hypoxia (Hyp, PIO2: 73 mmHg), while arterial blood gases and temperature (ABT) were simultaneously measured together with end‐tidal PCO2 (PETCO2). The Jones et al. equation tended to underestimate the temperature corrected (tc) PaCO2 during exercise in hypoxia, with greater deviation the lower the PaCO2tc (r = 0.39, P < 0.05). The new equation has been developed using a random‐effects regression analysis model, which allows predicting PaCO2tc both in normoxia and hypoxia: PaCO2tc = 8.607 + 0.716 × PETCO2 [R2 = 0.91; intercept SE = 1.022 (P < 0.001) and slope SE = 0.027 (P < 0.001)]. This equation may prove useful in noninvasive studies of brain hemodynamics, where an accurate estimation of PaCO2 is needed to calculate the end‐tidal‐to‐arterial PCO2 difference, which can be used as an index of pulmonary gas exchange efficiency.

Androgen receptor gene polymorphism influence fat accumulation: A longitudinal study from adolescence to adult age

To determine the influence of androgen receptor CAG and GGN repeat polymorphisms on fat mass and maximal fat oxidation (MFO), CAG and GGN repeat lengths were measured in 128 young boys, from which longitudinal data were obtained in 45 of them [mean ± SD: 12.8 ± 3.6 years old at recruitment, and 27.0 ± 4.8 years old at adult age]. Subjects were grouped as CAG short (CAGS) if harboring repeat lengths ≤  21, the rest as CAG long (CAGL); and GGN short (GGNS) if GGN repeat lengths ≤  23, or long if >  23 (GGNL). CAGS and GGNS were associated with lower adiposity than CAGL or GGNL (P < 0.05). There was an association between the logarithm of CAG repeats polymorphism and the changes of body mass (r = 0.34, P = 0.03). At adult age, CAGS men showed lower accumulation of total body and trunk fat mass, and lower resting metabolic rate (RMR) and MFO per kg of total lean mass compared with CAGL (P < 0.05). GGNS men also showed lower percentage of body fat (P < 0.05). In summary, androgen receptor CAG and GGN repeat polymorphisms are associated with RMR, MFO, fat mass, and its regional distribution in healthy male adolescents, influencing fat accumulation from adolescence to adult age.

Increased PIO2 at Exhaustion in Hypoxia Enhances Muscle Activation and Swiftly Relieves Fatigue: A Placebo or a PIO2 Dependent Effect?

To determine the level of hypoxia from which muscle activation (MA) is reduced during incremental exercise to exhaustion (IE), and the role played by PIO2 in this process, ten volunteers (21 ± 2 years) performed four IE in severe acute hypoxia (SAH) (PIO2 = 73 mmHg). Upon exhaustion, subjects were asked to continue exercising while the breathing gas mixture was swiftly changed to a placebo (73 mmHg) or to a higher PIO2 (82, 92, 99, and 142 mmHg), and the IE continued until a new exhaustion. At the second exhaustion, the breathing gas was changed to room air (normoxia) and the IE continued until the final exhaustion. MA, as reflected by the vastus medialis (VM) and lateralis (VL) EMG raw and normalized root mean square (RMSraw, and RMSNz, respectively), normalized total activation index (TAINz), and burst duration were 8–20% lower at exhaustion in SAH than in normoxia (P < 0.05). The switch to a placebo or higher PIO2 allowed for the continuation of exercise in all instances. RMSraw, RMSNz, and TAINz were increased by 5–11% when the PIO2 was raised from 73 to 92, or 99 mmHg, and VL and VM averaged RMSraw by 7% when the PIO2 was elevated from 73 to 142 mmHg (P < 0.05). The increase of VM-VL average RMSraw was linearly related to the increase in PIO2, during the transition from SAH to higher PIO2 (R2 = 0.915, P < 0.05). In conclusion, increased PIO2 at exhaustion reduces fatigue and allows for the continuation of exercise in moderate and SAH, regardless of the effects of PIO2 on MA. At task failure, MA is increased during the first 10 s of increased PIO2 when the IE is performed at a PIO2 close to 73 mmHg and the PIO2 is increased to 92 mmHg or higher. Overall, these findings indicate that one of the central mechanisms by which severe hypoxia may cause central fatigue and task failure is by reducing the capacity for reaching the appropriate level of MA to sustain the task. The fact that at exhaustion in severe hypoxia the exercise was continued with the placebo-gas mixture demonstrates that this central mechanism has a cognitive component.

Arterial to end-tidal Pco2 difference during exercise in normoxia and severe acute hypoxia: importance of blood temperature correction

Negative arterial to end‐tidal Pco2 differences ((a‐ET)Pco2) have been reported in normoxia. To determine the influence of blood temperature on (a‐ET)Pco2, 11 volunteers (21 ± 2 years) performed incremental exercise to exhaustion in normoxia (Nx, PIo2: 143 mmHg) and hypoxia (Hyp, PIo2: 73 mmHg), while arterial blood gases and temperature (ABT) were simultaneously measured together with end‐tidal Pco2 (PETco2). After accounting for blood temperature, the (a‐ET) Pco2 was reduced (in absolute values) from −4.2 ± 1.6 to −1.1 ± 1.5 mmHg in normoxia and from −1.7 ± 1.6 to 0.9 ± 0.9 mmHg in hypoxia (both P < 0.05). The temperature corrected (a‐ET)Pco2 was linearly related with absolute and relative exercise intensity, VO2, VCO2, and respiratory rate (RR) in normoxia and hypoxia (R2: 0.52–0.59). Exercise CO2 production and PETco2 values were lower in hypoxia than normoxia, likely explaining the greater (less negative) (a‐ET)Pco2 difference in hypoxia than normoxia (P < 0.05). At near‐maximal exercise intensity the (a‐ET)Pco2 lies close to 0 mmHg, that is, the mean Paco2 and the mean PETco2 are similar. The mean exercise (a‐ET)Pco2 difference is closely related to the mean A‐aDO2 difference (r = 0.90, P < 0.001), as would be expected if similar mechanisms perturb the gas exchange of O2 and CO2 during exercise. In summary, most of the negative (a‐ET)Pco2 values observed in previous studies are due to lack of correction of Paco2 for blood temperature. The absolute magnitude of the (a‐ET)Pco2 difference is lower during exercise in hypoxia than normoxia.

Severe energy deficit upregulates leptin receptors, leptin signaling, and PTP1B in human skeletal muscle

In obesity, leptin receptors (OBR) and leptin signaling in skeletal muscle are downregulated. To determine whether OBR and leptin signaling are upregulated with a severe energy deficit, 15 overweight men were assessed before the intervention (PRE), after 4 days of caloric restriction (3.2 kcal·kg body wt-1·day-1) in combination with prolonged exercise (CRE; 8 h walking + 45 min single-arm cranking/day) to induce an energy deficit of ~5,500 kcal/day, and following 3 days of control diet (isoenergetic) and reduced exercise (CD). During CRE, the diet consisted solely of whey protein (n = 8) or sucrose (n = 7; 0.8 g·kg body wt-1·day-1). Muscle biopsies were obtained from the exercised and the nonexercised deltoid muscles and from the vastus lateralis. From PRE to CRE, serum glucose, insulin, and leptin were reduced. OBR expression was augmented in all examined muscles associated with increased maximal fat oxidation. Compared with PRE, after CD, phospho-Tyr1141OBR, phospho-Tyr985OBR, JAK2, and phospho-Tyr1007/1008JAK2 protein expression were increased in all muscles, whereas STAT3 and phospho-Tyr705STAT3 were increased only in the arms. The expression of protein tyrosine phosphatase 1B (PTP1B) in skeletal muscle was increased by 18 and 45% after CRE and CD, respectively (P < 0.05). Suppressor of cytokine signaling 3 (SOCS3) tended to increase in the legs and decrease in the arm muscles (ANOVA interaction: P < 0.05). Myosin heavy chain I isoform was associated with OBR protein expression (r = -0.75), phospho-Tyr985OBR (r = 0.88), and phospho-Tyr705STAT3/STAT3 (r = 0.74). In summary, despite increased PTP1B expression, skeletal muscle OBR and signaling are upregulated by a severe energy deficit with greater response in the arm than in the legs likely due to SOCS3 upregulation in the leg muscles.NEW & NOTEWORTHY This study shows that the skeletal muscle leptin receptors and their corresponding signaling cascade are upregulated in response to a severe energy deficit, contributing to increase maximal fat oxidation. The responses are more prominent in the arm muscles than in the legs but partly blunted by whey protein ingestion and high volume of exercise. This occurs despite an increase of protein tyrosine phosphatase 1B protein expression, a known inhibitor of insulin and leptin signaling.