Effect of acute hypoxia on maximal oxygen uptake and maximal performance during leg and upper-body exercise in Nordic combined skiers

We examined the effect of normobaric hypoxia (3200 m) on maximal oxygen uptake (VO2max) and maximal power output (Pmax) during leg and upper-body exercise to identify functional and structural correlates of the variability in the decrement of VO2max (DeltaVO2max) and of maximal power output (DeltaPmax). Seven well trained male Nordic combined skiers performed incremental exercise tests to exhaustion on a cycle ergometer (leg exercise) and on a custom built doublepoling ergometer for cross-country skiing (upper-body exercise). Tests were carried out in normoxia (560 m) and normobaric hypoxia (3200 m); biopsies were taken from m. deltoideus. DeltaVO2max was not significantly different between leg (-9.1+/-4.9%) and upper-body exercise (-7.9+/-5.8%). By contrast, Pmax was significantly more reduced during leg exercise (-17.3+/-3.3%) than during upper-body exercise (-9.6+/-6.4%, p<0.05). Correlation analysis did not reveal any significant relationship between leg and upper-body exercise neither for DeltaVO2max nor for DeltaPmax. Furthermore, no relationship was observed between individual DeltaVO2max and DeltaPmax. Analysis of structural data of m. deltoideus revealed a significant correlation between capillary density and DeltaPmax (R=-0.80, p=0.03), as well as between volume density of mitochondria and DeltaPmax (R=-0.75, p=0.05). In conclusion, it seems that VO2max and Pmax are differently affected by hypoxia. The ability to tolerate hypoxia is a characteristic of the individual depending in part on the exercise mode. We present evidence that athletes with a high capillarity and a high muscular oxidative capacity are more sensitive to hypoxia.

Is hypoxia training good for muscles and exercise performance?

Altitude training has become very popular among athletes as a means to further increase exercise performance at sea level or to acclimatize to competition at altitude. Several approaches have evolved during the last few decades, with "live high-train low" and "live low-train high" being the most popular. This review focuses on functional, muscular, and practical aspects derived from extensive research on the "live low-train high" approach. According to this, subjects train in hypoxia but remain under normoxia for the rest of the time. It has been reasoned that exercising in hypoxia could increase the training stimulus. Hypoxia training studies published in the past have varied considerably in altitude (2300-5700 m) and training duration (10 days to 8 weeks) and the fitness of the subjects. The evidence from muscle structural, biochemical, and molecular findings point to a specific role of hypoxia in endurance training. However, based on the available performance capacity data such as maximal oxygen uptake (Vo(2)max) and (maximal) power output, hypoxia as a supplement to training is not consistently found to be advantageous for performance at sea level. Stronger evidence exists for benefits of hypoxic training on performance at altitude. "Live low-train high" may thus be considered when altitude acclimatization is not an option. In addition, the complex pattern of gene expression adaptations induced by supplemental training in hypoxia, but not normoxia, suggest that muscle tissue specifically responds to hypoxia. Whether and to what degree these gene expression changes translate into significant changes in protein concentrations that are ultimately responsible for observable structural or functional phenotypes remains open. It is conceivable that the global functional markers such as Vo(2)max and (maximal) power output are too coarse to detect more subtle changes that might still be functionally relevant, at least to high-level athletes.

Block training periodization in alpine skiing: effects of 11-day HIT on VO2max and performance

Attempting to achieve the high diversity of training goals in modern competitive alpine skiing simultaneously can be difficult and may lead to compromised overall adaptation. Therefore, we investigated the effect of block training periodization on maximal oxygen consumption (VO2max) and parameters of exercise performance in elite junior alpine skiers. Six female and 15 male athletes were assigned to high-intensity interval (IT, N = 13) or control training groups (CT, N = 8). IT performed 15 high-intensity aerobic interval (HIT) sessions in 11 days. Sessions were 4 x 4 min at 90-95% of maximal heart rate separated by 3-min recovery periods. CT continued their conventionally mixed training, containing endurance and strength sessions. Before and 7 days after training, subjects performed a ramp incremental test followed by a high-intensity time-to-exhaustion (tlim) test both on a cycle ergometer, a 90-s high-box jump test as well as countermovement (CMJ) and squat jumps (SJ) on a force plate. IT significantly improved relative VO2max by 6.0% (P < 0.01; male +7.5%, female +2.1%), relative peak power output by 5.5% (P < 0.01) and power output at ventilatory threshold 2 by 9.6% (P < 0.01). No changes occurred for these measures in CT. tlim remained unchanged in both groups. High-box jump performance was significantly improved in males of IT only (4.9%, P < 0.05). Jump peak power (CMJ -4.8%, SJ -4.1%; P < 0.01), but not height decreased in IT only. For competitive alpine skiers, block periodization of HIT offers a promising way to efficiently improve VO2max and performance. Compromised explosive jump performance might be associated with persisting muscle fatigue.

Acclimatization improves submaximal exercise economy at 5533m

We tested whether the better subjective exercise tolerance perceived by mountaineers after altitude acclimatization relates to enhanced exercise economy. Thirty-two mountaineers performed progressive bicycle exercise to exhaustion at 490 m and twice at 5533 m (days 6–7 and day 11), respectively, during an expedition to Mt. Muztagh Ata. Maximal work rate (Wmax) decreased from mean ± SD 356 ± 73 watts at 490 m to 191 ± 49 watts and 193 ± 45 watts at 5533 m, days 6–7 and day 11, respectively; corresponding maximal oxygen uptakes (VO2max) were 50.7 ± 9.5, 26.3 ± 5.6, 24.7 ± 7.0 mL/min/kg (P = 0.0001 5533 m vs 490 m). On days 6–7 (5533 m), VO2 at 75% Wmax (152 ± 37 watts) was 1.75 ± 0.45 L/min, oxygen saturation 68 ± 8%. On day 11 (5533 m), at the same submaximal work rate, VO2 was lower (1.61 ± 0.47 L/min, P < 0.027) indicating improved net efficiency; oxygen saturation was higher (74 ± 7%, P < 0.0004) but ratios of VO2 to work rate increments remained unchanged. On day 11, mountaineers climbed faster from 4497 m to 5533 m than on days 5–6 but perceived less effort (visual analog scale 50 ± 15 vs 57 ± 20, P = 0.006) and reduced symptoms of acute mountain sickness. We conclude that the better performance and subjective exercise tolerance after acclimatization were related to regression of acute mountain sickness and improved submaximal exercise economy because of lower metabolic demands for non-external work-performing functions.

Exercise training in normobaric hypoxia in endurance runners. III. Muscular adjustments of selected gene transcripts

We hypothesized that specific muscular transcript level adaptations participate in the improvement of endurance performances following intermittent hypoxia training in endurance-trained subjects. Fifteen male high-level, long-distance runners integrated a modified living low-training high program comprising two weekly controlled training sessions performed at the second ventilatory threshold for 6 wk into their normal training schedule. The athletes were randomly assigned to either a normoxic (Nor) (inspired O2 fraction = 20.9%, n = 6) or a hypoxic group exercising under normobaric hypoxia (Hyp) (inspired O2 fraction = 14.5%, n = 9). Oxygen uptake and speed at second ventilatory threshold, maximal oxygen uptake (VO2 max), and time to exhaustion (Tlim) at constant load at VO2 max velocity in normoxia and muscular levels of selected mRNAs in biopsies were determined before and after training. VO2 max (+5%) and Tlim (+35%) increased specifically in the Hyp group. At the molecular level, mRNA concentrations of the hypoxia-inducible factor 1alpha (+104%), glucose transporter-4 (+32%), phosphofructokinase (+32%), peroxisome proliferator-activated receptor gamma coactivator 1alpha (+60%), citrate synthase (+28%), cytochrome oxidase 1 (+74%) and 4 (+36%), carbonic anhydrase-3 (+74%), and manganese superoxide dismutase (+44%) were significantly augmented in muscle after exercise training in Hyp only. Significant correlations were noted between muscular mRNA levels of monocarboxylate transporter-1, carbonic anhydrase-3, glucose transporter-4, and Tlim only in the group of athletes who trained in hypoxia (P < 0.05). Accordingly, the addition of short hypoxic stress to the regular endurance training protocol induces transcriptional adaptations in skeletal muscle of athletic subjects. Expressional adaptations involving redox regulation and glucose uptake are being recognized as a potential molecular pathway, resulting in improved endurance performance in hypoxia-trained subjects.

Exercise training in normobaric hypoxia in endurance runners. I. Improvement in aerobic performance capacity

This study investigates whether a 6-wk intermittent hypoxia training (IHT), designed to avoid reductions in training loads and intensities, improves the endurance performance capacity of competitive distance runners. Eighteen athletes were randomly assigned to train in normoxia [Nor group; n = 9; maximal oxygen uptake (VO2 max) = 61.5 +/- 1.1 ml x kg(-1) x min(-1)] or intermittently in hypoxia (Hyp group; n = 9; VO2 max = 64.2 +/- 1.2 ml x kg(-1) x min(-1)). Into their usual normoxic training schedule, athletes included two weekly high-intensity (second ventilatory threshold) and moderate-duration (24-40 min) training sessions, performed either in normoxia [inspired O2 fraction (FiO2) = 20.9%] or in normobaric hypoxia (FiO2) = 14.5%). Before and after training, all athletes realized 1) a normoxic and hypoxic incremental test to determine VO2 max and ventilatory thresholds (first and second ventilatory threshold), and 2) an all-out test at the pretraining minimal velocity eliciting VO2 max to determine their time to exhaustion (T(lim)) and the parameters of O2 uptake (VO2) kinetics. Only the Hyp group significantly improved VO2 max (+5% at both FiO2, P < 0.05), without changes in blood O2-carrying capacity. Moreover, T(lim) lengthened in the Hyp group only (+35%, P < 0.001), without significant modifications of VO2 kinetics. Despite similar training load, the Nor group displayed no such improvements, with unchanged VO2 max (+1%, nonsignificant), T(lim) (+10%, nonsignificant), and VO2 kinetics. In addition, T(lim) improvements in the Hyp group were not correlated with concomitant modifications of other parameters, including VO2 max or VO2 kinetics. The present IHT model, involving specific high-intensity and moderate-duration hypoxic sessions, may potentialize the metabolic stimuli of training in already trained athletes and elicit peripheral muscle adaptations, resulting in increased endurance performance capacity.

Biologically relevant sex differences for fitness-related parameters in active octogenarians

The number of elderly people is growing in western populations, but only few maximal performance data exist for people >75 years, in particular for European octogenarians. This study was performed to characterize maximal performance of 55 independently living subjects (32 women, 81.1 +/- 3.4 years; 23 men, 81.7 +/- 2.9 years) with a focus on sex differences. Maximal performance was determined in a ramp test to exhaustion on a bicycle ergometer with ergospirometry, electrocardiogram and blood lactate measurements. Maximal isometric extension strength of the legs (MEL) was measured on a force platform in a seated position. Body composition was quantified by X-ray absorptiometry. In >25% of the subjects, serious cardiac abnormalities were detected during the ramp test with men more frequently being affected than women. Maximal oxygen consumption and power output were 18.2 +/- 3.2 versus 25.9 +/- 5.9 ml min(-1) kg(-1) and 66 +/- 12 versus 138 +/- 40 W for women versus men, with a significant sex difference for both parameters. Men outperformed women for MEL with 19.0 +/- 3.8 versus 13.6 +/- 3.3 N kg(-1). Concomitantly, we found a higher proportion of whole body fat in women (32.1 +/- 6.2%) compared to men (20.5 +/- 4.4%). Our study extends previously available maximal performance data for endurance and strength to independently living European octogenarians. As all sex-related differences were still apparent after normalization to lean body mass, it is concluded that it is essential to differentiate between female and male subjects when considering maximal performance parameters in the oldest segment of our population.

Exercise capacity and biventricular function in adult patients with repaired tetralogy of Fallot

BACKGROUND: Adult patients with repaired tetralogy of Fallot (rTOF) often have diminished exercise capacity. The primary objective of this study was to examine whether abnormalities of biventricular function play a role in exercise limitation in patients with rTOF. METHODS: This was a retrospective review of 99 adult patients with rTOF. Right ventricular (RV) and left ventricular (LV) function were assessed echocardiographically using the myocardial performance index (MPI). Maximal oxygen consumption (VO(2) Max) was measured during a level 1 cardiopulmonary exercise test. RESULTS: The mean age of the cohort was 34 +/- 11 years (50% females). Although most of the patients reported good functional capacity, the peak Vo(2)max was decreased at 22 +/- 6 mL/kg per minute (66% +/- 13% predicted Vo(2)max for age and sex). The mean RV and LV MPI were 0.30 +/- 0.07 and 0.42 +/- 0.09, respectively. In the multivariate model, higher RV MPI (P = .04) and LV MPI (P = .005) values, representing impaired ventricular function, were associated with diminished Vo(2)max. There was a significant correlation between the RV and LV MPI (r = 0.54, P = .001). CONCLUSIONS: Impairment of RV and LV function, as measured by MPI, is associated with diminished exercise capacity in patients with repaired tetralogy of Fallot. Furthermore, there is a linear relationship between the RV and LV function suggesting that ventricular interactions are contributing to the limited exercise capacity in this group of patients. Strategies aimed at preserving biventricular function or improving adverse ventricular interactions could help to improve functional capacity in these patients.

Training in hypoxia and its effects on skeletal muscle tissue

It is well established that local muscle tissue hypoxia is an important consequence and possibly a relevant adaptive signal of endurance exercise training in humans. It has been reasoned that it might be advantageous to increase this exercise stimulus by working in hypoxia. However, as long-term exposure to severe hypoxia has been shown to be detrimental to muscle tissue, experimental protocols were developed that expose subjects to hypoxia only for the duration of the exercise session and allow recovery in normoxia (live low-train high or hypoxic training). This overview reports data from 27 controlled studies using some implementation of hypoxic training paradigms. Hypoxia exposure varied between 2300 and 5700 m and training duration ranged from 10 days to 8 weeks. A similar number of studies was carried out on untrained and on trained subjects. Muscle structural, biochemical and molecular findings point to a specific role of hypoxia in endurance training. However, based on the available data on global estimates of performance capacity such as maximal oxygen uptake (VO2max) and maximal power output (Pmax), hypoxia as a supplement to training is not consistently found to be of advantage for performance at sea level. There is some evidence mainly from studies on untrained subjects for an advantage of hypoxic training for performance at altitude. Live low-train high may be considered when altitude acclimatization is not an option.

Effect of 6-month supervised exercise on low-density lipoprotein apolipoprotein B kinetics in patients with type 2 diabetes mellitus

Although low-density lipoprotein (LDL) cholesterol is often normal in patients with type 2 diabetes mellitus, there is evidence for a reduced fractional catabolic rate and consequently an increased mean residence time (MRT), which can increase atherogenic risk. The dyslipidemia and insulin resistance of type 2 diabetes mellitus can be improved by aerobic exercise, but effects on LDL kinetics are unknown. The effect of 6-month supervised exercise on LDL apolipoprotein B kinetics was studied in a group of 17 patients with type 2 diabetes mellitus (mean age, 56.8 years; range, 38-68 years). Patients were randomized into a supervised group, who had a weekly training session, and an unsupervised group. LDL kinetics were measured with an infusion of 1-(13)C leucine at baseline in all groups and after 6 months of exercise in the patients. Eight body mass index-matched nondiabetic controls (mean age, 50.3 years; range, 40-67 years) were also studied at baseline only. At baseline, LDL MRT was significantly longer in the diabetic patients, whereas LDL production rate and fractional clearance rates were significantly lower than in controls. Percentage of glycated hemoglobin A(1c), body mass index, insulin sensitivity measured by the homeostasis model assessment, and very low-density lipoprotein triglyceride decreased (P < .02) in the supervised group, with no change in the unsupervised group. After 6 months, LDL cholesterol did not change in either the supervised or unsupervised group; but there was a significant change in LDL MRT between groups (P < .05) that correlated positively with very low-density lipoprotein triglyceride (r = 0.51, P < .04) and negatively with maximal oxygen uptake, a measure of fitness (r = -0.51, P = .035), in all patients. The LDL production and clearance rates did not change in either group. This study suggests that a supervised exercise program can reduce deleterious changes in LDL MRT.

Seasonal variation of VO 2 max and the VO2-work rate relationship in elite Alpine skiers

PURPOSE: Alpine ski performance relates closely to both anaerobic and aerobic capacities. During their competitive season, skiers greatly reduce endurance and weight training, and on-snow training becomes predominant. To typify this shift, we compared exhaustive ramp cycling and squat (SJ) and countermovement jumping (CMJ) performance in elite males before and after their competitive season. RESULTS: In postseason compared with preseason: 1) maximal oxygen uptake (VO 2 max) normalized to bodyweight was higher (55.2 +/- 5.2 vs 52.7 +/- 3.6 mL x kg(-1) x min(-1), P < 0.01), but corresponding work rate (W) was unchanged; 2) at ventilatory thresholds (VT), absolute and relative work rates were similar but heart rates were lower; 3) VO2/W slope was greater (9.59 +/- 0.6 vs 9.19 +/- 0.4 mL O2 x min(-1) x W(-1), P = 0.02), with similar flattening (P < 0.01) above V T1 at both time points; and 4) jump height was greater in SJ (47.4 +/- 4.4 vs 44.7 +/- 4.3 cm, P < 0.01) and CMJ (52.7 +/- 4.6 vs 50.4 +/- 5.0 cm, P < 0.01). DISCUSSION: We believe that aerobic capacity and leg power were constrained in preseason and that improvements primarily reflected an in-season recovery from a fatigued state, which was caused by incongruous preseason training. Residual adaptations to high-altitude exposure in preseason could have also affected the results. Nonetheless, modern alpine skiing seemingly provides an ample cardiovascular training stimulus for skiers to maintain their aerobic capacities during the racing season. CONCLUSIONS: We conclude that aerobic fitness and leg explosiveness can be maintained in-season but may be compromised by heavy or excessive preseason training. In addition, ramp test V O2/W slope analysis could be useful for monitoring both positive and negative responses to training.

Metabolic and hormonal response to intermittent high-intensity and continuous moderate intensity exercise in individuals with type 1 diabetes: a randomised crossover study.

AIMS/HYPOTHESIS To investigate exercise-related fuel metabolism in intermittent high-intensity (IHE) and continuous moderate intensity (CONT) exercise in individuals with type 1 diabetes mellitus. METHODS In a prospective randomised open-label cross-over trial twelve male individuals with well-controlled type 1 diabetes underwent a 90 min iso-energetic cycling session at 50% maximal oxygen consumption ([Formula: see text]), with (IHE) or without (CONT) interspersed 10 s sprints every 10 min without insulin adaptation. Euglycaemia was maintained using oral (13)C-labelled glucose. (13)C Magnetic resonance spectroscopy (MRS) served to quantify hepatocellular and intramyocellular glycogen. Measurements of glucose kinetics (stable isotopes), hormones and metabolites complemented the investigation. RESULTS Glucose and insulin levels were comparable between interventions. Exogenous glucose requirements during the last 30 min of exercise were significantly lower in IHE (p = 0.02). Hepatic glucose output did not differ significantly between interventions, but glucose disposal was significantly lower in IHE (p < 0.05). There was no significant difference in glycogen consumption. Growth hormone, catecholamine and lactate levels were significantly higher in IHE (p < 0.05). CONCLUSIONS/INTERPRETATION IHE in individuals with type 1 diabetes without insulin adaptation reduced exogenous glucose requirements compared with CONT. The difference was not related to increased hepatic glucose output, nor to enhanced muscle glycogen utilisation, but to decreased glucose uptake. The lower glucose disposal in IHE implies a shift towards consumption of alternative substrates. These findings indicate a high flexibility of exercise-related fuel metabolism in type 1 diabetes, and point towards a novel and potentially beneficial role of IHE in these individuals. TRIAL REGISTRATION ClinicalTrials.gov NCT02068638 FUNDING: Swiss National Science Foundation (grant number 320030_149321/) and R&A Scherbarth Foundation (Switzerland).

Effect of remifentanil on mitochondrial oxygen consumption of cultured human hepatocytes

During sepsis, liver dysfunction is common, and failure of mitochondria to effectively couple oxygen consumption with energy production has been described. In addition to sepsis, pharmacological agents used to treat septic patients may contribute to mitochondrial dysfunction. This study addressed the hypothesis that remifentanil interacts with hepatic mitochondrial oxygen consumption. The human hepatoma cell line HepG2 and their isolated mitochondria were exposed to remifentanil, with or without further exposure to tumor necrosis factor-α (TNF-α). Mitochondrial oxygen consumption was measured by high-resolution respirometry, Caspase-3 protein levels by Western blotting, and cytokine levels by ELISA. Inhibitory κBα (IκBα) phosphorylation, measurement of the cellular ATP content and mitochondrial membrane potential in intact cells were analysed using commercial ELISA kits. Maximal cellular respiration increased after one hour of incubation with remifentanil, and phosphorylation of IκBα occurred, denoting stimulation of nuclear factor κB (NF-κB). The effect on cellular respiration was not present at 2, 4, 8 or 16 hours of incubation. Remifentanil increased the isolated mitochondrial respiratory control ratio of complex-I-dependent respiration without interfering with maximal respiration. Preincubation with the opioid receptor antagonist naloxone prevented a remifentanil-induced increase in cellular respiration. Remifentanil at 10× higher concentrations than therapeutic reduced mitochondrial membrane potential and ATP content without uncoupling oxygen consumption and basal respiration levels. TNF-α exposure reduced respiration of complex-I, -II and -IV, an effect which was prevented by prior remifentanil incubation. Furthermore, prior remifentanil incubation prevented TNF-α-induced IL-6 release of HepG2 cells, and attenuated fragmentation of pro-caspase-3 into cleaved active caspase 3 (an early marker of apoptosis). Our data suggest that remifentanil increases cellular respiration of human hepatocytes and prevents TNF-α-induced mitochondrial dysfunction. The results were not explained by uncoupling of mitochondrial respiration.

Dissociated lateralization of transient and sustained blood oxygen level-dependent signal components in human primary auditory cortex

Among other auditory operations, the analysis of different sound levels received at both ears is fundamental for the localization of a sound source. These so-called interaural level differences, in animals, are coded by excitatory-inhibitory neurons yielding asymmetric hemispheric activity patterns with acoustic stimuli having maximal interaural level differences. In human auditory cortex, the temporal blood oxygen level-dependent (BOLD) response to auditory inputs, as measured by functional magnetic resonance imaging (fMRI), consists of at least two independent components: an initial transient and a subsequent sustained signal, which, on a different time scale, are consistent with electrophysiological human and animal response patterns. However, their specific functional role remains unclear. Animal studies suggest these temporal components being based on different neural networks and having specific roles in representing the external acoustic environment. Here we hypothesized that the transient and sustained response constituents are differentially involved in coding interaural level differences and therefore play different roles in spatial information processing. Healthy subjects underwent monaural and binaural acoustic stimulation and BOLD responses were measured using high signal-to-noise-ratio fMRI. In the anatomically segmented Heschl's gyrus the transient response was bilaterally balanced, independent of the side of stimulation, while in opposite the sustained response was contralateralized. This dissociation suggests a differential role at these two independent temporal response components, with an initial bilateral transient signal subserving rapid sound detection and a subsequent lateralized sustained signal subserving detailed sound characterization.

Postexercise fat intake repletes intramyocellular lipids but no faster in trained than in sedentary subjects

The hypotheses that postexercise replenishment of intramyocellular lipids (IMCL) is enhanced by endurance training and that it depends on fat intake were tested. Trained and untrained subjects exercised on a treadmill for 2 h at 50% peak oxygen consumption, reducing IMCL by 26-22%. During recovery, they were fed 55% (high fat) or 15% (low fat) lipid energy diets. Muscle substrate stores were estimated by (1)H (IMCL)- and (13)C (glycogen)-magnetic resonance spectroscopy in tibialis anterior muscle before and after exercise. Resting IMCL content was 71% higher in trained than untrained subjects and correlated significantly with glycogen content. Both correlated positively with indexes of insulin sensitivity. After 30 h on the high-fat diet, IMCL concentration was 30-45% higher than preexercise, whereas it remained 5-17% lower on the low-fat diet. Training status had no significant influence on IMCL replenishment. Glycogen was restored within a day with both diets. We conclude that fat intake postexercise strongly promotes IMCL repletion independently of training status. Furthermore, replenishment of IMCL can be completed within a day when fat intake is sufficient.