Live high, train low - influence on resting and post-exercise hepcidin levels.

The post-exercise hepcidin response during prolonged (>2 weeks) hypoxic exposure is not well understood. We compared plasma hepcidin levels 3 h after exercise [6 × 1000 m at 90% of maximal aerobic running velocity (vVO2max )] performed in normoxia and normobaric hypoxia (3000 m simulate altitude) 1 week before, and during 14 days of normobaric hypoxia [196.2 ± 25.6 h (median: 200.8 h; range: 154.3-234.8 h) at 3000 m simulated altitude] in 10 well-trained distance runners (six males, four females). Venous blood was also analyzed for hepcidin after 2 days of normobaric hypoxia. Hemoglobin mass (Hbmass ) was measured via CO rebreathing 1 week before and after 14 days of hypoxia. Hepcidin was suppressed after 2 (Cohen's d = -2.3, 95% confidence interval: [-2.9, -1.6]) and 14 days of normobaric hypoxia (d = -1.6 [-2.6, -0.6]). Hepcidin increased from baseline, 3 h post-exercise in normoxia (d = 0.8 [0.2, 1.3]) and hypoxia (d = 0.6 [0.3, 1.0]), both before and after exposure (normoxia: d = 0.7 [0.3, 1.2]; hypoxia: d = 1.3 [0.4, 2.3]). In conclusion, 2 weeks of normobaric hypoxia suppressed resting hepcidin levels, but did not alter the post-exercise response in either normoxia or hypoxia, compared with the pre-exposure response.

Stability of athlete blood passport parameters during air freight.

INTRODUCTION: Fluctuations in ambient temperature and pressure, as well as physical jostling, may affect the stability of whole blood samples transported by air freight. The aim of this study was to characterize the stability of key blood variables during air freight and to investigate whether vibration or reduced pressure alone affected results. METHODS: Over a 72-h interval, we evaluated the stability of full blood count indices (plus reticulocytes) in tubes that were air-freighted a total of 2, 10 and 28 h. We also examined the impact of 24 h of reduced atmospheric pressure (750 hpa or approximately 2500 m.a.s.l) and vibration (5 Hz). Samples were measured on a Sysmex XT-2000i instrument. RESULTS: The two key variables in the context of antidoping (haemoglobin concentration, reticulocytes) remained stable over a 72-h period regardless of the duration of air freight. Atmospheric pressure and vibration had no discernible effect. CONCLUSION: Whole blood samples stored in NanoCool devices can be relied upon to remain stable for at least 72 h despite interim air freight.

The effects of injury and illness on haemoglobin mass.

This study sought to quantify the effects of reduced training, surgery and changes in body mass on haemoglobin mass (Hbmass) in athletes. Hbmass of 15 athletes (6 males, 9 females) was measured 9±6 (mean±SD) times over 162±198 days, during reduced training following injury or illness. Additionally, body mass (n=15 athletes) and episodes of altitude training (n=2), iron supplementation (n=5), or surgery (n=3) were documented. Training was recorded and compared with pre-injury levels. Analysis used linear mixed models for ln(Hbmass), with Sex, Altitude, Surgery, Iron, Training and log(Body Mass) as fixed effects, and Athlete as a fixed and random effect. Reduced training and surgery led to 2.3% (p=0.02) and 2.7% (p=0.04) decreases in Hbmass, respectively. Altitude and iron increased Hbmass by 2.4% (p=0.03) and 4.2% (p=0.05), respectively. The effect of changes in body mass on Hbmass was not statistically significant (p=0.435).The estimates for the effects of surgery and altitude on Hbmass should be confirmed by future research using a larger sample of athletes. These estimates could be used to inform the judgements of experts examining athlete biological passports, improving their interpretation of Hbmass perturbations, which athletes claim are related to injury, thereby protecting innocent athletes from unfair sanctioning.

Stability of athlete passport parameters during extended storage.

INTRODUCTION: Extended intervals between sample collection and analyses render athlete's whole-blood specimens collected in the field for antidoping purposes susceptible to storage degradation. The aim of this study was to characterize the stability of key blood variables under different storage durations and temperatures. METHODS: We evaluated stability of full blood count indices (plus reticulocytes) in individual tubes left undisturbed during 36, 48, 72, 96, 120, 144 and 168 h of storage at approximately 4, 6 and 12 °C. Samples were measured on a Sysmex XT-2000i instrument. RESULTS: The two key variables in the context of antidoping (haemoglobin concentration, reticulocytes) were stable for at least 168 h, except under 12 °C (stable 48 h only). Volume-dependent variables changed in a predictable manner that enabled a nomogram to be generated to predict original values provided storage duration and temperature were known. CONCLUSION: Key blood results can be relied upon for at least 7 days if storage temperature is kept at 4-6 °C.

Spurious Hb mass increases following exercise.

Sensitivity of the Athlete Blood Passport for blood doping could be improved by including total haemoglobin mass (Hb(mass)), but this measure may be unreliable immediately following strenuous exercise. We examined the stability of Hb(mass) following ultra-endurance triathlon (3.8 km swim, 180 km bike, 42.2 km run). 26 male sub-elite triathletes, 18 Racers and 8 Controls, were tested for Hb(mass) using CO re-breathing, twice 1-5 days apart. Racers were measured before and 1-3 h after the triathlon. Controls did no vigorous exercise on either test day. Serum haptoglobin concentration and urine haemoglobin concentration were measured to assess intravascular haemolysis. There was a 3.2% (p<0.01) increase in Racers' Hb(mass) from pre-race (976 g ± 14.6%, mean ±% coefficient of variation) to post-race (1 007 g ± 13.8%), as opposed to a - 0.5% decrease in Controls (pre-race 900 g ± 13.9%, post-race 896 g ± 12.4%). Haptoglobin was - 67% (p<0.01) reduced in Racers (pre-race 0.48 g / L ± 150%, post-race 0.16 g / L ± 432%), compared to - 6% reduced in Controls (pre-race 1.08 g / L ± 37%, post-race 1.02 g / L ± 37%). Decreased serum haptoglobin concentration in Racers, which is suggestive of mild intravascular blood loss, was contrary to the apparent Hb(mass) increase post-race. Ultra-endurance triathlon racing may confound the accuracy of post-exercise Hb(mass) measures, possibly due to splenic contraction or an increased rate of CO diffusion to intramuscular myoglobin.

Detraining decreases Hb(mass) of triathletes.

Haemoglobin mass (Hbmass) determination using CO rebreathing may assist to detect illegal blood doping practices, however variations in Hbmass with periods of intensive training and detraining must be quantified. This study aimed to determine the effect of a 30-day period of detraining on Hbmass in ultra-endurance triathletes. 9 male recreational triathletes (29-44 years) participated in the study. Hbmass was assessed using CO rebreathing 30 days and 10 days before an ultra-endurance triathlon and after ~10, 20 and 30 days of detraining following the race. V˙O2max was assessed 10 days before the race and also after the 30-day detraining period, which consisted of an 87% reduction in training hours. After 30-days of detraining there was a 3.1% decrease in mean Hbmass from 868±99 to 840±94 g, (p=0.03), and a 4.7% decrease in mean V˙O2max from 4.83±0.29 to 4.61±0.41 L/min as well as a 2.8% increase of body mass from 75.1±6.4 to 77.1±6.1 kg and a 28% increase in skinfold total from 43.9±14.2 to 55.1±14.0 mm. Individual decreases in Hbmass following detraining would need to be considered if using Hbmass for anti-doping purposes.

No change in hemoglobin mass after 40 days of physical activity in previously untrained adults.

A high hemoglobin mass (Hb(mass)) is associated with a high maximum aerobic power (VO(2max)), however, the extent to which Hb(mass) is influenced by training is currently unclear. Accordingly, this study monitored changes in Hb(mass) and VO(2max) in 12 previously untrained adults (aged 18-25 years) following 40 days of regular physical activity. Hb(mass) and VO(2max) were assessed at the start and end of a 40-day physical activity program, which comprised of approximately 40 min of daily, moderate-intensity physical activity. Relative VO(2max) increased by 11.3%, yet there was no significant change in relative Hb(mass) (1.7%) and body mass (0.2%) during the 40-day period. There was a significant correlation between Hb(mass) and VO(2max) at the start of the study (r=0.58, P=0.05), but not between the change in relative VO(2max) and the change in relative Hb(mass) (r=-0.07, P=0.83). Our results support the concept of relative stability in Hb(mass) with approximately 1 month of moderate-intensity physical activity suggesting that Hb(mass) may be used for talent identification and possibly for anti-doping purposes.

Quality control technique to reduce the variability of longitudinal measurement of hemoglobin mass.

The sensitivity of the athlete blood passport to detect blood doping may be improved by the inclusion of total hemoglobin mass (Hb(mass)), but the comparability of Hb(mass) from different laboratories is unknown. To optimize detection sensitivity, the analytical variability associated with Hb(mass) measurement must be minimized. The aim of this study was to investigate the efficacy of using quality controls to minimize the variation in Hb(mass) between laboratories. Three simulated laboratories were set up in one location. Nine participants completed three carbon monoxide (CO) re-breathing tests in each laboratory. One participant completed two CO re-breathing tests in each laboratory. Simultaneously, quality controls containing Low (1-3%) and High (8-11%) concentrations of percent carboxyhemoglobin (%HbCO) were measured to compare hemoximeters in each laboratory. Linear mixed modeling was used to estimate the within-subject variation in Hb(mass), expressed as the coefficient of variation, and to estimate the effect of different laboratories. The analytic variation of Hb(mass) was 2.4% when tests were conducted in different laboratories, which reduced to 1.6% when the model accounted for between-laboratory differences. Adjustment of Hb(mass) values using quality controls achieved a comparable analytic variation of 1.7%. The majority of between-laboratory variation in Hb(mass) originated from the difference between hemoximeters, which could be eliminated using appropriate quality controls.

Detecting autologous blood transfusions: a comparison of three passport approaches and four blood markers.

Blood passport has been suggested as an indirect tool to detect various kinds of blood manipulations. Autologous blood transfusions are currently undetectable, and the objective of this study was to examine the sensitivities of different blood markers and blood passport approaches in order to determine the best approach to detect autologous blood transfusions. Twenty-nine subjects were transfused with either one (n=8) or three (n=21) bags of autologous blood. Hemoglobin concentration ([Hb]), percentage of reticulocytes (%ret) and hemoglobin mass (Hbmass) were measured 1 day before reinfusion and six times after reinfusion. The sensitivity and specificity of a novel marker, Hbmr (based on Hbmass and %ret), was evaluated together with [Hb], Hbmass and OFF-hr by different passport methods. Our novel Hbmr marker showed superior sensitivity in detecting the highest dosage of transfused blood, with OFF-hr showing equal or superior sensitivities at lower dosages. Hbmr and OFF-hr showed superior but equal sensitivities from 1 to 4 weeks after transfusion compared with [Hb] and Hbmass, with Hbmass being the only tenable prospect to detect acute transfusions. Because autologous blood transfusions can be an acute practice with blood withdrawal and reinfusion within a few days, Hbmass seems to be the only option for revealing this practice.

Time course of haemoglobin mass during 21 days live high:train low simulated altitude.

The aim of this study was to determine the time course of changes in haemoglobin mass (Hb(mass)) in well-trained cyclists in response to live high:train low (LHTL). Twelve well-trained male cyclists participated in a 3-week LHTL protocol comprising 3,000 m simulated altitude for ~14 h/day. Prior to LHTL duplicate baseline measurements were made of Hb(mass), maximal oxygen consumption (VO(2max)) and serum erythropoietin (sEPO). Hb(mass) was measured weekly during LHTL and twice in the week thereafter. There was a 3.3% increase in Hb(mass) and no change in VO(2max) after LHTL. The mean Hb(mass) increased at a rate of ~1% per week and this was maintained in the week after cessation of LHTL. The sEPO concentration peaked after two nights of LHTL but there was only a trivial correlation (r = 0.04, P = 0.89) between the increase in sEPO and the increase in Hb(mass). Athletes seeking to gain erythropoietic benefits from moderate altitude need to spend >12 h/day in hypoxia.

Improved running economy and increased hemoglobin mass in elite runners after extended moderate altitude exposure.

There is conflicting evidence whether hypoxia improves running economy (RE), maximal O(2) uptake (V(O)(2max)), haemoglobin mass (Hb(mass)) and performance, and what total accumulated dose is necessary for effective adaptation. The aim of this study was to determine the effect of an extended hypoxic exposure on these physiological and performance measures. Nine elite middle distance runners were randomly assigned to a live high-train low simulated altitude group (ALT) and spent 46+/-8 nights (mean+/-S.D.) at 2860+/-41m. A matched control group (CON, n=9) lived and trained near sea level ( approximately 600m). ALT decreased submaximal V(O)(2) (Lmin(-1)) (-3.2%, 90% confidence intervals, -1.0% to -5.2%, p=0.02), increased Hb(mass) (4.9%, 2.3-7.6%, p=0.01), decreased submaximal heart rate (-3.1%, -1.8% to -4.4%, p=0.00) and had a trivial increase in V(O)(2max) (1.5%, -1.6 to 4.8; p=0.41) compared with CON. There was a trivial correlation between change in Hb(mass) and change in V(O)(2max) (r=0.04, p=0.93). Hypoxic exposure of approximately 400h was sufficient to improve Hb(mass), a response not observed with shorter exposures. Although total O(2) carrying capacity was improved, the mechanism(s) to explain the lack of proportionate increase in V(O)(2max) were not identified.

Live and/or sleep high:train low, using normobaric hypoxia.

The increase in oxygen transport elicited by several weeks of exposure to moderate to high altitude is used to increase physical performance when returning to sea level. However, many studies have shown that aerobic performance may not increase at sea level after a training block at high altitude. Subsequently, the concept of living high and training low was introduced in the early 1990s and was further modified to include simulated altitude using hypobaric or normobaric hypoxia. Review is given of the main studies that have used this procedure. Hematological changes are limited to insignificant or moderate increase in red cell mass, depending on the "dose" of hypoxia. Maximal aerobic performance is increased when the exposure to hypoxia is at least over 18 days. Submaximal performance and running economy have been found increased in several, but not all, studies. The tolerance (fatigue, sleep, immunological status, cardiac function) is good when the altitude or simulated altitude is not higher than 3000 m. Virtually no data are available about the effect of this procedure upon anaerobic performance. The wide spread of these techniques deserves further investigations.

Preparation for football competition at moderate to high altitude.

Analysis of approximately 100 years of home-and-away South American World Cup matches illustrate that football competition at moderate/high altitude (>2000 m) favors the home team, although this is more than compensated by the likelihood of sea-level teams winning at home against the same opponents who have descended from altitude. Nevertheless, the home team advantage at altitudes above approximately 2000 m may reflect that traditionally, teams from sea level or low altitude have not spent 1-2 weeks acclimatizing at altitude. Despite large differences between individuals, in the first few days at high altitude (e.g. La Paz, 3600 m) some players experience symptoms of acute mountain sickness (AMS) such as headache and disrupted sleep, and their maximum aerobic power (VO2max) is approximately 25% reduced while their ventilation, heart rate and blood lactate during submaximal exercise are elevated. Simulated altitude for a few weeks before competition at altitude can be used to attain partial ventilatory acclimation and ameliorated symptoms of AMS. The variety of simulated altitude exposures usually created with enriched nitrogen mixtures of air include resting or exercising for a few hours per day or sleeping approximately 8 h/night in hypoxia. Preparation for competition at moderate/high altitude by training at altitude is probably superior to simulated exposure; however, the optimal duration at moderate/high altitude is unclear. Preparing for 1-2 weeks at moderate/high altitude is a reasonable compromise between the benefits associated with overcoming AMS and partial restoration of VO2max vs the likelihood of detraining.

The effect of acute simulated moderate altitude on power, performance and pacing strategies in well-trained cyclists.

Athletes regularly compete at 2,000-3,000 m altitude where peak oxygen consumption (VO2peak) declines approximately 10-20%. Factors other than VO2peak including gross efficiency (GE), power output, and pacing are all important for cycling performance. It is therefore imperative to understand how all these factors and not just VO2peak are affected by acute hypobaric hypoxia to select athletes who can compete successfully at these altitudes. Ten well-trained, non-altitude-acclimatised male cyclists and triathletes completed cycling tests at four simulated altitudes (200, 1,200, 2,200, 3,200 m) in a randomised, counter-balanced order. The exercise protocol comprised 5 x 5-min submaximal efforts (50, 100, 150, 200 and 250 W) to determine submaximal VO2 and GE and, after 10-min rest, a 5-min maximal time-trial (5-minTT) to determine VO2peak and mean power output (5-minTT(power)). VO2peak declined 8.2 +/- 2.0, 13.9 +/- 2.9 and 22.5 +/- 3.8% at 1,200, 2,200 and 3,200 m compared with 200 m, respectively, P < 0.05. The corresponding decreases in 5-minTT(power) were 5.8 +/- 2.9, 10.3 +/- 4.3 and 19.8 +/- 3.5% (P < 0.05). GE during the 5-minTT was not different across the four altitudes. There was no change in submaximal VO2 at any of the simulated altitudes, however, submaximal efficiency decreased at 3,200 m compared with both 200 and 1,200 m. Despite substantially reduced power at simulated altitude, there was no difference in pacing at the four altitudes for athletes whose first trial was at 200 or 1,200 m; whereas athletes whose first trial was at 2,200 or 3,200 m tended to mis-pace that effort. In conclusion, during the 5-minTT there was a dose-response effect of hypoxia on both VO2peak and 5-minTT(power) but no effect on GE.

Effects of exercise intensity and duration on the excess post-exercise oxygen consumption.

Recovery from a bout of exercise is associated with an elevation in metabolism referred to as the excess post-exercise oxygen consumption (EPOC). A number of investigators in the first half of the last century reported prolonged EPOC durations and that the EPOC was a major component of the thermic effect of activity. It was therefore thought that the EPOC was a major contributor to total daily energy expenditure and hence the maintenance of body mass. Investigations conducted over the last two or three decades have improved the experimental protocols used in the pioneering studies and therefore have more accurately characterized the EPOC. Evidence has accumulated to suggest an exponential relationship between exercise intensity and the magnitude of the EPOC for specific exercise durations. Furthermore, work at exercise intensities >or=50-60% VO2max stimulate a linear increase in EPOC as exercise duration increases. The existence of these relationships with resistance exercise at this stage remains unclear because of the limited number of studies and problems with quantification of work intensity for this type of exercise. Although the more recent studies do not support the extended EPOC durations reported by some of the pioneering investigators, it is now apparent that a prolonged EPOC (3-24 h) may result from an appropriate exercise stimulus (submaximal: >or=50 min at >or=70% VO2max; supramaximal: >or=6 min at >or=105% VO2max). However, even those studies incorporating exercise stimuli resulting in prolonged EPOC durations have identified that the EPOC comprises only 6-15% of the net total oxygen cost of the exercise. But this figure may need to be increased when studies utilizing intermittent work bouts are designed to allow the determination of rest interval EPOCs, which should logically contribute to the EPOC determined following the cessation of the last work bout. Notwithstanding the aforementioned, the earlier research optimism regarding an important role for the EPOC in weight loss is generally unfounded. This is further reinforced by acknowledging that the exercise stimuli required to promote a prolonged EPOC are unlikely to be tolerated by non-athletic individuals. The role of exercise in the maintenance of body mass is therefore predominantly mediated via the cumulative effect of the energy expenditure during the actual exercise.

Interspersed normoxia during live high, train low interventions reverses an early reduction in muscle Na+, K +ATPase activity in well-trained athletes.

Hypoxia and exercise each modulate muscle Na(+), K(+)ATPase activity. We investigated the effects on muscle Na(+), K(+)ATPase activity of only 5 nights of live high, train low hypoxia (LHTL), 20 nights consecutive (LHTLc) versus intermittent LHTL (LHTLi), and acute sprint exercise. Thirty-three athletes were assigned to control (CON, n = 11), 20-nights LHTLc (n = 12) or 20-nights LHTLi (4 x 5-nights LHTL interspersed with 2-nights CON, n = 10) groups. LHTLc and LHTLi slept at a simulated altitude of 2,650 m (F(I)O(2) 0.1627) and lived and trained by day under normoxic conditions; CON lived, trained, and slept in normoxia. A quadriceps muscle biopsy was taken at rest and immediately after standardised sprint exercise, before (Pre) and after 5-nights (d5) and 20-nights (Post) LHTL interventions and analysed for Na(+), K(+)ATPase maximal activity (3-O-MFPase) and content ([(3)H]-ouabain binding). After only 5-nights LHTLc, muscle 3-O-MFPase activity declined by 2% (P < 0.05). In LHTLc, 3-O-MFPase activity remained below Pre after 20 nights. In contrast, in LHTLi, this small initial decrease was reversed after 20 nights, with restoration of 3-O-MFPase activity to Pre-intervention levels. Plasma [K(+)] was unaltered by any LHTL. After acute sprint exercise 3-O-MFPase activity was reduced (12.9 +/- 4.0%, P < 0.05), but [(3)H]-ouabain binding was unchanged. In conclusion, maximal Na(+), K(+)ATPase activity declined after only 5-nights LHTL, but the inclusion of additional interspersed normoxic nights reversed this effect, despite athletes receiving the same amount of hypoxic exposure. There were no effects of consecutive or intermittent nightly LHTL on the acute decrease in Na(+), K(+)ATPase activity with sprint exercise effects or on plasma [K(+)] during exercise.

Acute weight loss followed by an aggressive nutritional recovery strategy has little impact on on-water rowing performance.

OBJECTIVES: To assess the influence of moderate, acute weight loss on on-water rowing performance when aggressive nutritional recovery strategies were used in the two hours between weigh in and racing. METHODS: Competitive rowers (n = 17) undertook three on-water 1800 m time trials under cool conditions (mean (SD) temperature 8.4 (2.0) degrees C), each separated by 48 hours. No weight limit was imposed for the first time trial--that is, unrestricted body mass (UNR1). However, one of the remaining two trials followed a 4% loss in body mass in the previous 24 hours (WT(-4%)). No weight limit was imposed for the other trial (UNR2). Aggressive nutritional recovery strategies (WT(-4%), 2.3 g/kg carbohydrate, 34 mg/kg Na+, and 28.4 ml/kg fluid; UNR, ad libitum) were used in the first 90 minutes of the two hours between weigh in and performance trials. RESULTS: WT(-4%) had only a small and statistically non-significant effect on the on-water time trial performance (mean 1.0 second, 95% confidence interval (CI) -0.9 to 2.8; p = 0.29) compared with UNR. This was despite a significant decrease in plasma volume at the time of weigh in for WT(-4%) compared with UNR (-9.2%, 95% CI -12.8% to -5.6%; p<0.001). CONCLUSIONS: Acute weight loss of up to 4% over 24 hours, when combined with aggressive nutritional recovery strategies, can be undertaken with minimal impact on on-water rowing performance, at least in cool conditions.

Sleep in athletes undertaking protocols of exposure to nocturnal simulated altitude at 2650 m.

A popular method to attempt to enhance performance is for athletes to sleep at natural or simulated moderate altitude (SMA) when training daily near sea level. Based on our previous observation of periodic breathing in athletes sleeping at SMA, we hypothesised that athletes' sleep quality would also suffer with hypoxia. Using two typical protocols of nocturnal SMA (2650 m), we examined the effect on the sleep physiology of 14 male endurance-trained athletes. The selected protocols were Consecutive (15 successive exposure nights) and Intermittent (3x 5 successive exposure nights, interspersed with 2 normoxic nights) and athletes were randomly assigned to follow either one. We monitored sleep for two successive nights under baseline conditions (B; normoxia, 600 m) and then at weekly intervals (nights 1, 8 and 15 (N1, N8 and N15, respectively)) of the protocols. Since there was no significant difference in response between the protocols being followed (based on n=7, for each group) we are unable to support a preference for either one, although the likelihood of a Type II error must be acknowledged. For all athletes (n=14), respiratory disturbance and arousal responses between B and N1, although large in magnitude, were highly individual and not statistically significant. However, SpO2 decreased at N1 versus B (p<0.001) and remained lower on N8 (p<0.001) and N15 (p<0.001), not returning to baseline level. Compared to B, arousals were more frequent on N8 (p=0.02) and N15 (p=0.01). The percent of rapid eye movement sleep (REM) increased from N1 to N8 (p=0.03) and N15 (p=0.01). Overall, sleeping at 2650 m causes sleep disturbance in susceptible athletes, yet there was some improvement in REM sleep over the study duration.

Chronic intermittent hypoxia and incremental cycling exercise independently depress muscle in vitro maximal Na+-K+-ATPase activity in well-trained athletes.

Athletes commonly attempt to enhance performance by training in normoxia but sleeping in hypoxia [live high and train low (LHTL)]. However, chronic hypoxia reduces muscle Na(+)-K(+)-ATPase content, whereas fatiguing contractions reduce Na(+)-K(+)-ATPase activity, which each may impair performance. We examined whether LHTL and intense exercise would decrease muscle Na(+)-K(+)-ATPase activity and whether these effects would be additive and sufficient to impair performance or plasma K(+) regulation. Thirteen subjects were randomly assigned to two fitness-matched groups, LHTL (n = 6) or control (Con, n = 7). LHTL slept at simulated moderate altitude (3,000 m, inspired O(2) fraction = 15.48%) for 23 nights and lived and trained by day under normoxic conditions in Canberra (altitude approximately 600 m). Con lived, trained, and slept in normoxia. A standardized incremental exercise test was conducted before and after LHTL. A vastus lateralis muscle biopsy was taken at rest and after exercise, before and after LHTL or Con, and analyzed for maximal Na(+)-K(+)-ATPase activity [K(+)-stimulated 3-O-methylfluorescein phosphatase (3-O-MFPase)] and Na(+)-K(+)-ATPase content ([(3)H]ouabain binding sites). 3-O-MFPase activity was decreased by -2.9 +/- 2.6% in LHTL (P < 0.05) and was depressed immediately after exercise (P < 0.05) similarly in Con and LHTL (-13.0 +/- 3.2 and -11.8 +/- 1.5%, respectively). Plasma K(+) concentration during exercise was unchanged by LHTL; [(3)H]ouabain binding was unchanged with LHTL or exercise. Peak oxygen consumption was reduced in LHTL (P < 0.05) but not in Con, whereas exercise work was unchanged in either group. Thus LHTL had a minor effect on, and incremental exercise reduced, Na(+)-K(+)-ATPase activity. However, the small LHTL-induced depression of 3-O-MFPase activity was insufficient to adversely affect either K(+) regulation or total work performed.