Changes in cycling economy and fractional utilization of V̇O2peak during a 40-min maximal effort exercise test with acute hypobaric hypoxia corresponding to 2800 m of altitude.

INTRODUCTION: Peak oxygen uptake (V̇O2peak ) declines by ~7% per 1000 m of increasing altitude, whereas exercise performance seems reduced to a lesser extent. For example, 800-10 000 m track and field performances are decreased by 0.4%-2.4% above 1000 m as compared to below and some studies show similar drops in cycling performance. A greater decline in V̇O2peak than in endurance performance with altitude suggests a higher fractional utilization of V̇O2peak (%V̇O2peak ). Therefore, we hypothesized that the %V̇O2peak is higher with acute hypoxic exposure than near sea level. METHODS: Sixteen lowlanders (8 women, age: 31 ± 7 years [mean ± SD], body mass: 68 ± 8 kg, V̇O2peak : 60 ± 8 mL min-1 kg-1 ) underwent cycling testing in a hypobaric hypoxic chamber on 6 test days, three conducted at 300 m and three at 2800 m of acute altitude. At both altitudes, V̇O2peak was determined, and during a 40-min all out maximal effort time trial (TT), mean power output (MPO) and mean V̇O2 (%V̇O2peak ) were assessed. RESULTS: V̇O2peak decreased by 11.2 ± 3.0% (p < 0.001), while MPO during the TT declined by 10.7 ± 3.1% (p < 0.001) at 2800 m as compared to 300 m. During the TT, %V̇O2peak was higher at altitude, corresponding to 75.9 ± 4.5% at 300 m and 78.8 ± 4.2% at 2800 m (p = 0.011), and cycling economy (mL O2 kJ-1 ) was poorer (+3.4 ± 2.7%, p < 0.001). CONCLUSION: The %V̇O2peak was higher during a cycling TT at 2800 m of altitude than near sea level, while cycling economy was poorer. This resulted in a similar reduction in performance and V̇O2peak . Future studies should address the physiological mechanisms underlying the elevated %V̇O2peak .

Distinguishing left ventricular hypertrophy from hypertrophic cardiomyopathy in adolescents: a longitudinal observation study.

AIMS: Echocardiographic characteristics to distinguish physiological left ventricular (LV) hypertrophy from pathology are warranted in early adolescent athletes. This study aimed to explore the phenotype, progression, and potential grey zone of LV hypertrophy during adolescence in athletes and hypertrophic cardiomyopathy (HCM) genotype-positive patients. METHODS AND RESULTS: In this longitudinal observation study, we compared seventy-six 12-year-old athletes with 55 age-matched and sex-matched HCM genotype-positive patients. Echocardiographic parameters were evaluated by using paediatric reference values (Z-scores). Hypertrophic cardiomyopathy genotype-positive patients were included if they had no or mild LV hypertrophy [maximum wall thickness <13 mm, Z-score <6 for interventricular septum diameter (ZIVSd), or posterior wall thickness]. We collected clinical data, including data on cardiac events. The mean follow-up-time was 3.2 ± 0.8 years. At baseline, LV hypertrophy was found in 28% of athletes and 21% of HCM genotype-positive patients (P = 0.42). Septum thickness values were similar (ZIVSd 1.4 ± 0.9 vs. 1.0 ± 1.3, P = 0.08) and increased only in HCM genotype-positive patients {ZIVSd progression rate -0.17 [standard error (SE) 0.05], P = 0.002 vs. 0.30 [SE 0.10], P = 0.001}. Left ventricular volume Z-scores (ZLVEDV) were greater in athletes [ZLVEDV 1.0 ± 0.6 vs. -0.1 ± 0.8, P < 0.001; ZLVEDV progression rate -0.05 (SE 0.04), P = 0.21 vs. -0.06 (SE 0.04), P = 0.12]. Cardiac arrest occurred in two HCM genotype-positive patients (ages 13 and 14), with ZIVSd 8.2-11.5. CONCLUSION: Left ventricular hypertrophy was found in a similar proportion in early adolescence but progressed only in HCM genotype-positive patients. A potential grey zone of LV hypertrophy ranged from a septum thickness Z-score of 2.0 to 3.3. Left ventricular volumes remained larger in athletes. Evaluating the progression of wall thickness and volume may help clinicians distinguish physiological LV hypertrophy from early HCM.

It is important to distinguish exercise-induced cardiac left ventricular (LV) hypertrophy from hypertrophic cardiomyopathy (HCM), because athletes with HCM may have an increased risk of sudden cardiac death. Limited data are available on this distinction in adolescent athletes. Therefore, we performed a longitudinal observation study comparing the development of LV hypertrophy during adolescence in athletes and HCM genotype­positive patients. In early adolescence, LV hypertrophy was found in a similar proportion of athletes and HCM genotype­positive patients, with a potential grey zone ranging from a septum thickness Z-score of 2.0 to 3.3. After 3 years of follow-up, LV hypertrophy had progressed only in HCM genotype­positive patients, while athletes had larger LV volumes throughout the study period.Evaluation of LV volume and septum thickness progression may assist clinicians in distinguishing exercise-induced LV hypertrophy from early HCM disease in adolescents.

Determinants and reference values for blood volume and total hemoglobin mass in women and men.

Blood volume (BV) is an important clinical parameter and is usually reported per kg of body mass (BM). When fat mass is elevated, this underestimates BV/BM. One aim was to study if differences in BV/BM related to sex, age, and fitness would decrease if normalized to lean body mass (LBM). The analysis included 263 women and 319 men (age: 10-93 years, body mass index: 14-41 kg/m2 ) and 107 athletes who underwent assessment of BV and hemoglobin mass (Hbmass ), body composition, and cardiorespiratory fitness. BV/BM was 25% lower (70.3 ± 11.3 and 80.3 ± 10.8 mL/kgBM ) in women than men, respectively, whereas BV/LBM was 6% higher in women (110.9 ± 12.5 and 105.3 ± 11.2 mL/kgLBM ). Hbmass /BM was 34% lower (8.9 ± 1.4 and 11.5 ± 11.2 g/kgBM ) in women than in men, respectively, but only 6% lower (14.0 ± 1.5 and 14.9 ± 1.5 g/kgLBM )/LBM. Age did not affect BV. Athlete's BV/BM was 17.2% higher than non-athletes, but decreased to only 2.5% when normalized to LBM. Of the variables analyzed, LBM was the strongest predictor for BV (R2 = .72, p < .001) and Hbmass (R2 = .81, p < .001). These data may only be valid for BV/Hbmass when assessed by CO re-breathing. Hbmass /LBM could be considered a valuable clinical matrix in medical care aiming to normalize blood homeostasis.

Effects of adding high-intensity training during an 8-week period on maximal oxygen uptake in 12-year-old youth athletes.

PURPOSE: Maximal oxygen uptake (V̇O2max ) increases during adolescence parallel to the increase in fat-free mass (FFM). How much endurance training adds to this effect is still controversial. Our aim was to investigate if inclusion of high-intensity training (HIT) during an 8-week training period was superior to low-intensity strength and coordination training in 12-year-old youth athletes concerning the effect on V̇O2max . METHODS: Thirty-five cross-country skiers were randomized into a HIT group (ET) and a strength and coordination group (SC), while 29 less active peers served as controls for growth and maturation (C). Anthropometrics and V̇O2max were assessed before and after the training period, and level of physical activity and training were monitored with accelerometers, training logs and a questionnaire. RESULTS: The number of weekly training sessions were higher for ET (4.6 ± 1.2) and SC (4.1 ± 1.0) compared with C (1.8 ± 2.0) (p < 0.01), with only ET conducting HIT sessions (1.9 ± 0.2 per week). C spent more time sedentary and less time in moderate and vigorous activity compared with ET (p < 0.05). All groups had a similar %-change pre-post in absolute V̇O2max (mL min-1 ) of 6% ± 6% for ET (p < 0.01), 5% ± 7 for SC (p = 0.14), and 5% ± 13% for C (p = 0.03), with no significant differences between groups. V̇O2max relative to FFM did not change significantly for any groups. CONCLUSION: The change in V̇O2max paralleled the change in FFM for all groups, questioning the effect of HIT on V̇O2max over an 8-week period in youth athletes.

Correction: Effects of Aerobic Exercise on Cardiorespiratory Fitness, Cardiovascular Risk Factors, and Patient-Reported Outcomes in Long-Term Breast Cancer Survivors: Protocol for a Randomized Controlled Trial.

[This corrects the article DOI: 10.2196/45244.].

Determinants of the maximal functional reserve during repeated supramaximal exercise by humans: The roles of Nrf2/Keap1, antioxidant proteins, muscle phenotype and oxygenation.

When high-intensity exercise is performed until exhaustion a "functional reserve" (FR) or capacity to produce power at the same level or higher than reached at exhaustion exists at task failure, which could be related to reactive oxygen and nitrogen species (RONS)-sensing and counteracting mechanisms. Nonetheless, the magnitude of this FR remains unknown. Repeated bouts of supramaximal exercise at 120% of VO2max interspaced with 20s recovery periods with full ischaemia were used to determine the maximal FR. Then, we determined which muscle phenotypic features could account for the variability in functional reserve in humans. Exercise performance, cardiorespiratory variables, oxygen deficit, and brain and muscle oxygenation (near-infrared spectroscopy) were measured, and resting muscle biopsies were obtained from 43 young healthy adults (30 males). Males and females had similar aerobic (VO2max per kg of lower extremities lean mass (LLM): 166.7 ± 17.1 and 166.1 ± 15.6 ml kg LLM-1.min-1, P = 0.84) and anaerobic fitness (similar performance in the Wingate test and maximal accumulated oxygen deficit when normalized to LLM). The maximal FR was similar in males and females when normalized to LLM (1.84 ± 0.50 and 2.05 ± 0.59 kJ kg LLM-1, in males and females, respectively, P = 0.218). This FR depends on an obligatory component relying on a reserve in glycolytic capacity and a putative component generated by oxidative phosphorylation. The aerobic component depends on brain oxygenation and phenotypic features of the skeletal muscles implicated in calcium handling (SERCA1 and 2 protein expression), oxygen transport and diffusion (myoglobin) and redox regulation (Keap1). The glycolytic component can be predicted by the protein expression levels of pSer40-Nrf2, the maximal accumulated oxygen deficit and the protein expression levels of SOD1. Thus, an increased capacity to modulate the expression of antioxidant proteins involved in RONS handling and calcium homeostasis may be critical for performance during high-intensity exercise in humans.

Effects of Aerobic Exercise on Cardiorespiratory Fitness, Cardiovascular Risk Factors, and Patient-Reported Outcomes in Long-Term Breast Cancer Survivors: Protocol for a Randomized Controlled Trial.

BACKGROUND: Anthracycline-based chemotherapy has been mainstay of adjuvant breast cancer therapy for decades. Although effective, anthracyclines place long-term breast cancer survivors at risk of late effects, such as reduced cardiorespiratory fitness and increased risk of cardiovascular disease. Previous research has shown beneficial effects of exercise training on cardiorespiratory fitness, but the effects of exercise on limiting factors for cardiorespiratory fitness, cardiovascular risk factors, and patient-reported outcomes in long-term survivors are less clear. Whether previous exposure to breast cancer therapy modulates the effects of exercise is also unknown. OBJECTIVE: The primary aim of the CAUSE (Cardiovascular Survivors Exercise) trial is to examine the effect of aerobic exercise on cardiorespiratory fitness in anthracycline-treated long-term breast cancer survivors. Secondary aims are to examine effects of exercise training on limiting factors for cardiorespiratory fitness, cardiovascular risk factors, and patient-reported outcomes, and to compare baseline values and effects of exercise training between similar-aged women with and those without prior breast cancer. A third aim is to examine the 24-month postintervention effects of aerobic exercise on primary and secondary outcomes. METHODS: The CAUSE trial is a 2-armed randomized controlled trial, where 140 long-term breast cancer survivors, 8-12 years post diagnosis, are assigned to a 5-month nonlinear aerobic exercise program with 3 weekly sessions or to standard care. Seventy similar-aged women with no history of cancer will undergo the same exercise program. Cardiorespiratory fitness measured as peak oxygen consumption (VO2peak), limiting factors for VO2peak (eg, cardiac function, pulmonary function, hemoglobin mass, blood volume, and skeletal muscle characteristics), cardiovascular risk factors (eg, hypertension, diabetes, dyslipidemia, obesity, physical activity level, and smoking status), and patient-reported outcomes (eg, body image, fatigue, mental health, and health-related quality of life) will be assessed at baseline, post intervention, and 24 months post intervention. RESULTS: A total of 209 patients were included from October 2020 to August 2022, and postintervention assessments were completed in January 2023. The 24-month follow-up will be completed in February 2025. CONCLUSIONS: The findings from the CAUSE trial will provide novel scientific understanding of the potential benefits of exercise training in long-term breast cancer survivors. TRIAL REGISTRATION: ClinicalTrials.gov NCT04307407; https://clinicaltrials.gov/ct2/show/NCT04307407. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/45244.

Young athlete's growing heart: sex differences in cardiac adaptation to exercise training during adolescence.

BACKGROUND: Athlete's heart is a condition of exercise-induced cardiac remodelling. Adult male endurance athletes more often remodel beyond reference values. The impact of sex on remodelling through adolescence remains unclear. Paediatric reference values do not account for patient sex or exercise history. We aimed to study the effect of sex on cardiac remodelling throughout adolescence. METHODS: We recruited 76 male (M) and female (F) 12-year-old cross-country skiers in a longitudinal cohort study. Echocardiography was performed and analysed according to guidelines at age 12 (48 M, 28 F), 15 (34 M, 14 F) and 18 (23 M, 11 F). Repeated echocardiographic measurements were analysed by linear mixed model regression. RESULTS: Males displayed greater indexed left ventricular end-diastolic volumes (LV EDVi) from age 12 (M 81±7 vs F 76±7, mL/m², p≤0.01), and progressed further until follow-up at age 18 (M 2.3±9.7 vs F -3.9±4.5 ΔmL/m², p≤0.01). LV EDVi remained above adult upper reference values in both groups. Males increased LV Mass Index from age 12 to 18 (M 33±27 vs F 4±19, Δg/m², p≤0.01). Males displayed LV mass above paediatric reference values at ages 15 and 18. A subset of males (35%) and females (25%) displayed wall thickness above paediatric reference values at age 12. Cardiac function was normal. There was no sex difference in exercise hours. CONCLUSION: Sex-related differences in athlete's heart were evident from age 12, and progressed throughout adolescence. Remodelling beyond reference values was more frequent than previously reported, particularly affecting males. Age, sex and exercise history may assist clinicians in distinguishing exercise-induced remodelling from pathology in adolescents.

Aerobic exercise training resets the human skeletal muscle methylome 10 years after breast cancer treatment and survival.

Cancer survivors suffer impairments in skeletal muscle in terms of reduced mass and function. Interestingly, human skeletal muscle possesses an epigenetic memory of earlier stimuli, such as exercise. Long-term retention of epigenetic changes in skeletal muscle following cancer survival and/or exercise training has not yet been studied. We, therefore, investigated genome-wide DNA methylation (methylome) in skeletal muscle following a 5-month, 3/week aerobic-training intervention in breast cancer survivors 10-14 years after diagnosis and treatment. These results were compared to breast cancer survivors who remained untrained and to age-matched controls with no history of cancer, who undertook the same training intervention. Skeletal muscle biopsies were obtained from 23 females before(pre) and after(post) the 5-month training period. InfiniumEPIC 850K DNA methylation arrays and RT-PCR for gene expression were performed. The breast cancer survivors displayed a significant retention of increased DNA methylation (i.e., hypermethylation) at a larger number of differentially methylated positions (DMPs) compared with healthy age-matched controls pre training. Training in cancer survivors led to an exaggerated number of DMPs with a hypermethylated signature occurring at non-regulatory regions compared with training in healthy age-matched controls. However, the opposite occurred in important gene regulatory regions, where training in cancer survivors elicited a considerable reduction in methylation (i.e., hypomethylation) in 99% of the DMPs located in CpG islands within promoter regions. Importantly, training was able to reverse the hypermethylation identified in cancer survivors back toward a hypomethylated signature that was observed pre training in healthy age-matched controls at 300 (out of 881) of these island/promoter-associated CpGs. Pathway enrichment analysis identified training in cancer survivors evoked a predominantly hypomethylated signature in pathways associated with cell cycle, DNA replication/repair, transcription, translation, mTOR signaling, and the proteosome. Differentially methylated region (DMR) analysis also identified genes: BAG1, BTG2, CHP1, KIFC1, MKL2, MTR, PEX11B, POLD2, S100A6, SNORD104, and SPG7 as hypermethylated in breast cancer survivors, with training reversing these CpG island/promoter-associated DMRs toward a hypomethylated signature. Training also elicited a largely different epigenetic response in healthy individuals than that observed in cancer survivors, with very few overlapping changes. Only one gene, SIRT2, was identified as having altered methylation in cancer survivors at baseline and after training in both the cancer survivors and healthy controls. Overall, human skeletal muscle may retain a hypermethylated signature as long as 10-14 years after breast cancer treatment/survival. Five months of aerobic training reset the skeletal muscle methylome toward signatures identified in healthy age-matched individuals in gene regulatory regions.

Individual variations in pre-altitude hemoglobin mass influence hemoglobin mass responses to repeated altitude sojourns.

INTRODUCTION: Previous studies have shown variable within-subject hemoglobin mass (Hbmass ) responses to altitude training. We investigated whether Hbmass responses depend on individual variations in pre-altitude Hbmass during repeated altitude sojourns. METHODS: Nine elite endurance athletes carried out 3-5 altitude sojourns over 17 ± 10 months (mean ± 95% confidence interval), at an altitude of 1976 ± 62 m, for 21 ± 1 days, and a total hypoxic dose of 989 ± 46 km·h, with Hbmass assessed before and after each sojourn (carbon monoxide rebreathing). The individual mean baseline was calculated as the mean of all pre-altitude Hbmass values for an athlete, and it was investigated whether the percent deviation from the individual mean baseline affected the altitude-induced Hbmass response. RESULTS: On average, Hbmass increased by 3.4 ± 1.1% (p < 0.001) from pre- to post-altitude. The intra-individual changes in Hbmass were highly inconsistent (coefficient of variation, CV: 88%), and we found no relationship between Hbmass changes in successive altitude sojourns (r = 0.01; p = 0.735). However, the percent increase in Hbmass was highly correlated with the pre-altitude Hbmass , expressed as the percent deviation from the individual mean baseline (y = -0.7x + 3.4; r = 0.75; p < 0.001). Linear mixed-model analysis confirmed a -0.6 ± 0.2% smaller increase in Hbmass for each 1% higher pre-altitude Hbmass than the individual mean baseline (p < 0.001) after adjusting for the covariates hypoxic dose (p = 0.032) and the relative Hbmass (g·kg-1 body weight; p = 0.031). CONCLUSION: Individual variations in pre-altitude Hbmass significantly influence the athletes' Hbmass responses to repeated altitude sojourns, with a potentiated response after traveling to altitude with a low pre-altitude Hbmass .

Kinematic differences between uphill roller skiing and on-snow skiing using the V2 skating technique.

PURPOSE: Roller skiing is the primary sport-specific training and testing mode during pre-competition periods for cross-country skiers, biathletes, and Nordic combined athletes. The present study aimed to compare the kinematics between uphill roller skiing and on-snow skiing using the V2 sub-technique. METHODS: In a cross-over design, nine well-trained male skiers performed short trials (< 40 s) at constant inclination (8.0°), speed (3.0 m‧s-1), and controlled rolling/gliding friction on asphalt (in the fall), on the treadmill (in the fall and winter), and during on-snow skiing (in the winter). Kinematic data were collected using a validated inertial measurement unit system. RESULTS: Repeated-measures ANOVAs revealed no differences between treadmill and asphalt roller skiing. Further, including on-snow skiing showed moderate to good reliability (ICC ≥ 0.63, p ≤ 0.001) for ground-contact temporal variables. However, on-snow skiing moderately increased hip range of motion around the longitudinal axis (22.2 ± 7.7° vs. 14.1 ± 4.7°), lateral hip displacement (44.1 ± 7.1 cm vs. 37.2 ± 6.6 cm) and pole push times (422 ± 41 ms vs. 386 ± 31 ms), and on-snow skiing was characterized by altered hip rotational patterns compared to roller skiing. CONCLUSION: V2 roller ski skating simulates on-snow ski skating to a large extent, but the mechanical properties of the skis and/or surface hardness systematically alter skiers' hip movements and pole push times. This implies a potential for equipment optimization to increase training specificity during pre-competition periods and highlights a need for future studies to examine the kinematic effects of snow hardness on all sub-techniques.

Angiotensin-Converting Enzyme 2 (SARS-CoV-2 receptor) expression in human skeletal muscle.

The study aimed to determine the levels of skeletal muscle angiotensin-converting enzyme 2 (ACE2, the SARS-CoV-2 receptor) protein expression in men and women and assess whether ACE2 expression in skeletal muscle is associated with cardiorespiratory fitness and adiposity. The level of ACE2 in vastus lateralis muscle biopsies collected in previous studies from 170 men (age: 19-65 years, weight: 56-137 kg, BMI: 23-44) and 69 women (age: 18-55 years, weight: 41-126 kg, BMI: 22-39) was analyzed in duplicate by western blot. VO2 max was determined by ergospirometry and body composition by DXA. ACE2 protein expression was 1.8-fold higher in women than men (p = 0.001, n = 239). This sex difference disappeared after accounting for the percentage of body fat (fat %), VO2 max per kg of legs lean mass (VO2 max-LLM) and age (p = 0.47). Multiple regression analysis showed that the fat % (ß = 0.47) is the main predictor of the variability in ACE2 protein expression in skeletal muscle, explaining 5.2% of the variance. VO2 max-LLM had also predictive value (ß = 0.09). There was a significant fat % by VO2 max-LLM interaction, such that for subjects with low fat %, VO2 max-LLM was positively associated with ACE2 expression while as fat % increased the slope of the positive association between VO2 max-LLM and ACE2 was reduced. In conclusion, women express higher amounts of ACE2 in their skeletal muscles than men. This sexual dimorphism is mainly explained by sex differences in fat % and cardiorespiratory fitness. The percentage of body fat is the main predictor of the variability in ACE2 protein expression in human skeletal muscle.

Effects of 150- and 450-mL Acute Blood Losses on Maximal Oxygen Uptake and Exercise Capacity.

PURPOSE: This study investigated whether maximal oxygen uptake (V˙O2max) and exercise capacity are affected by small acute blood loss (150 mL) and elucidated compensatory mechanisms. METHODS: Thirteen male subjects (V˙O2max, 63 ± 9 mL·kg-1·min-1; mean ± SD) performed incremental exercise to exhaustion on a cycle ergometer in three experimental conditions: in euvolemia (control; blood volume [BV], 6.0 ± 0.7 L) and immediately after acute BV reductions of 150 mL (BVR150mL) and 450 mL (BVR450mL). Changes in plasma volume (PV) and BV during exercise were calculated from hematocrit, hemoglobin concentration, and hemoglobin mass (carbon monoxide rebreathing). RESULTS: The reduction in V˙O2max per milliliter of BVR was 2.5-fold larger after BVR450mL compared with BVR150mL (-0.7 ± 0.3 vs -0.3 ± 0.6 mL·min-1·mL-1, P = 0.029). V˙O2max was not significantly changed after BVR150mL (-1% ± 2%, P = 0.124) but reduced by 7% ± 3% after BVR450mL (P < 0.001) compared with control. Peak power output only decreased after BVR450mL (P < 0.001). At maximal exercise, BV was restored after BVR150mL compared with control (-50 ± 185 mL, P = 0.375) attributed to PV restoration, which was, however, insufficient in restoring BV after BVR450mL (-281 ± 184 mL, P < 0.001). The peak heart rate tended to increase (3 ± 5 bpm, P = 0.062), whereas the O2 pulse (-2 ± 1 mL per beat, P < 0.001) and vastus lateralis tissue oxygenation index (-4% ± 8% points, P = 0.080) were reduced after BVR450mL, suggesting decreased stroke volume and increased leg O2 extraction. CONCLUSION: The deteriorations of V˙O2max and of maximal exercise capacity accelerate with the magnitude of acute blood loss, likely because of a rapid PV restoration sufficient to establish euvolemia after a small but not after a moderate blood loss.

Functional reserve and sex differences during exercise to exhaustion revealed by post-exercise ischaemia and repeated supramaximal exercise.

KEY POINTS: Females have lower fatigability than males during single limb isometric and dynamic contractions, but whether sex-differences exist during high-intensity whole-body exercise remains unknown. This study shows that males and females respond similarly to repeated supramaximal whole-body exercise, and that at task failure a large functional reserve remains in both sexes. Using post-exercise ischaemia with repeated exercise, we have shown that this functional reserve depends on the glycolytic component of substrate-level phosphorylation and is almost identical in both sexes. Metaboreflex activation during post-exercise ischaemia and the O2 debt per kg of active lean mass are also similar in males and females after supramaximal exercise. Females have a greater capacity to extract oxygen during repeated supramaximal exercise and reach lower PETCO2 , experiencing a larger drop in brain oxygenation than males, without apparent negative repercussion on performance. Females had no faster recovery of performance after accounting for sex differences in lean mass. ABSTRACT: The purpose of this study was to ascertain what mechanisms explain sex differences at task failure and to determine whether males and females have a functional reserve at exhaustion. Exercise performance, cardiorespiratory variables, oxygen deficit, and brain and muscle oxygenation were determined in 18 males and 18 females (21-36 years old) in two sessions consisting of three bouts of constant-power exercise at 120% of V̇O2max until exhaustion interspaced by 20 s recovery periods. In one of the two sessions, the circulation of both legs was occluded instantaneously (300 mmHg) during the recovery periods. Females had a higher muscle O2 extraction during fatiguing supramaximal exercise than males. Metaboreflex activation, and lean mass-adjusted O2 deficit and debt were similar in males and females. Compared to males, females reached lower PETCO2 and brain oxygenation during supramaximal exercise, without apparent negative consequences on performance. After the occlusions, males and females were able to restart exercising at 120% of V̇O2max , revealing a similar functional reserve, which depends on glycolytic component of substrate-level phosphorylation and its rate of utilization. After ischaemia, muscle O2 extraction was increased, and muscle V̇O2 was similarly reduced in males and females. The physiological response to repeated supramaximal exercise to exhaustion is remarkably similar in males and females when differences in lean mass are considered. Both sexes fatigue with a large functional reserve, which depends on the glycolytic energy supply, yet females have higher oxygen extraction capacity, but reduced PETCO2 and brain oxygenation.

Longitudinal changes in maximal oxygen uptake in adolescent girls and boys with different training backgrounds.

The purpose of this study was to investigate the effects of high-volume endurance training on the development of maximal oxygen uptake (VO2max ) in physically active boys and girls between the ages of 12 and 15 years, using a longitudinal design. The children participated in organized training in sports clubs for an average of 7-10 hours per week, with one group undertaking a high volume of endurance training (~7 hours per week; End boys, n = 23 and End girls, n = 17) and the other group having a primary focus on technical and tactical skill development, undertaking low volumes of endurance training (~1.6 hours per week; non-End boys, n = 29 and non-End girls, n = 9). VO2max and anthropometrics were assessed at age 12, 13, and 15. At age 12, VO2max was 58.9 (5.6), 65.5 (7.2), 56.5 (6.5), and 58.8 (7.9) mL·kg-1 ·min-1 in End girls, End boys, non-End girls, and non-End boys, respectively. Over the three years, there was no difference between the training groups in the development of VO2max independent of scaling. In boys, VO2max relative to body mass (BM) did not change from age 12 to 15, while VO2max tended to decrease relative to fat-free mass (FFM). In girls, VO2max relative to BM decreased slightly from age 12 to 15, with no changes over the years relative to FFM. The present longitudinal study suggests that in growing active children during puberty, high volumes of systematic endurance training do not have an additional effect on VO2max compared with similar volume of training mainly aiming at developing motor skills.

Impact of baseline serum ferritin and supplemental iron on altitude-induced hemoglobin mass response in elite athletes.

The present study explored the impact of pre-altitude serum (s)-ferritin and iron supplementation on changes in hemoglobin mass (ΔHbmass) following altitude training. Measures of Hbmass and s-ferritin from 107 altitude sojourns (9-28 days at 1800-2500 m) with world-class endurance athletes (males n = 41, females n = 25) were analyzed together with iron supplementation and self-reported illness. Altitude sojourns with a hypoxic dose [median (range)] of 1169 (912) km·h increased Hbmass (mean ± SD) 36 ± 38 g (3.7 ± 3.7%, p < 0.001) and decreased s-ferritin -11 (190) µg·L-1 (p = 0.001). Iron supplements [27 (191) mg·day-1 ] were used at 45 sojourns (42%), while only 11 sojourns (10%) were commenced with s-ferritin <35 µg/L. Hbmass increased by 4.6 ± 3.7%, 3.4 ± 3.3%, 4.2 ± 4.3%, and 2.9 ± 3.4% with pre-altitude s-ferritin ≤35 µg·L-1 , 36-50 µg·L-1 , 51-100 µg·L-1 , and >100 µg·L-1 , respectively, with no group difference (p = 0.400). Hbmass increased by 4.1 ± 3.9%, 3.0 ± 3.0% and 3.7 ± 4.7% without, ≤50 mg·day-1 or >50 mg·day-1 supplemental iron, respectively (p = 0.399). Linear mixed model analysis revealed no interaction between pre-altitude s-ferritin and iron supplementation on ΔHbmass (p = 0.906). However, each 100 km·h increase in hypoxic dose augmented ΔHbmass by an additional 0.4% (95% CI: 0.1-0.7%; p = 0.012), while each 1 g·kg-1 higher pre-altitude Hbmass reduced ΔHbmass by -1% (-1.6 to -0.5; p < 0.001), and illness lowered ΔHbmass by -5.7% (-8.3 to -3.1%; p < 0.001). In conclusion, pre-altitude s-ferritin or iron supplementation were not related to the altitude-induced increase in Hbmass (3.7%) in world-class endurance athletes with clinically normal iron stores.

From talented child to elite athlete: The development of cardiac morphology and function in a cohort of endurance athletes from age 12 to 18.

BACKGROUND: Adult athletes undergo cardiac adaptions in what is known as the "athlete's heart". Cardiac adaptations in young athletes have not been described in longitudinal studies but have previously been believed to be uniform in nature. METHODS: Seventy-six cross-country skiers were assessed at age 12. Forty-eight (63%) completed the first follow-up at age 15 and 36 (47%) the second follow-up at age 18. Comprehensive exercise data were collected. Echocardiography with three-dimensional measurements and cardiopulmonary exercise testing were performed at all time points. The cohort was divided into active and former endurance athletes, with an eight hours of weekly endurance exercise cut-off at age 18. RESULTS: The athletes underwent eccentric remodelling between ages 12 and 15, and concentric remodelling between ages 15 and 18. At age 18, the active endurance athletes had greater increases in inter-ventricular wall thickness (1.8 ± 1.4 Δmm vs 0.6 ± 1.0 Δmm, p < 0.05), left ventricular (LV) posterior wall thickness (1.6 ± 1.2 Δmm vs 0.8 ± 0.8 Δmm, p < 0.05), LV mass (63 ± 30 Δg vs 27 ± 21 Δg, p < 0.01), right ventricular (RV) end-diastolic area (3.4 ± 4.0 Δcm2 vs 0.6 ± 3.5Δ cm2, p < 0.05), RV end-systolic area (1.0 ± 2.3 Δcm2 vs -0.9 ± 2.0 Δcm2, p < 0.05) and left atrial volume (24 ± 21 ΔmL vs 6±10 ΔmL, p < 0.05) and had greater indexed maximal oxygen uptake (66.3 ± 7.4 mL/min/kg vs 57.1 ± 8.2 mL/min/kg, p < 0.01). There was no significant difference for LV volumes. CONCLUSION: This study finds a shift in the development of the young athlete's heart. Between ages 12 and 15, the active endurance athletes underwent eccentric remodelling. This dynamic switched to concentric remodelling between ages 15 and 18.

Achieving energy balance with a high-fat meal does not enhance skeletal muscle adaptation and impairs glycaemic response in a sleep-low training model.

NEW FINDINGS: What is the central question of this study? Does achieving energy balance mainly with ingested fat in a 'sleep-low' model of training with low muscle glycogen affect the early training adaptive response during recovery? What is the main finding and its importance? Replenishing the energy expended during exercise mainly from ingested fat to achieve energy balance in a 'sleep-low' model does not enhance the response of skeletal muscle markers of early adaptation to training and impairs glycaemic control the morning after compared to training with low energy availability. These findings are important for optimizing post-training dietary recommendations in relation to energy balance and macronutrient intake. ABSTRACT: Training with low carbohydrate availability (LCHO) has been shown to acutely enhance endurance training skeletal muscle response, but the concomitant energy deficit (ED) in LCHO interventions has represented a confounding factor in past research. This study aimed at determining if achieving energy balance with high fat (EB-HF) acutely enhances the adaptive response in LCHO compared to ED with low fat (ED-LF). In a crossover design, nine well-trained males completed a 'sleep-low' protocol: on day 1 they cycled to deplete muscle glycogen while reaching a set energy expenditure (30 kcal (kg of fat free mass (FFM))-1 ). Post-exercise, low carbohydrate, protein-matched meals completely (EB-HF, 30 kcal (kg FFM)-1 ) or partially (ED-LF, 9 kcal (kg FFM)-1 ) replaced the energy expended, with the majority of energy derived from fat in EB-HF. In the morning of day 2, participants exercised fasted, and skeletal muscle and blood samples were collected and a carbohydrate-protein drink was ingested at 0.5 h recovery. Muscle glycogen showed no treatment effect (P < 0.001) and decreased from 350 ± 98 to 192 ± 94 mmol (kg dry mass)-1 between rest and 0.5 h recovery. Phosphorylation status of the mechanistic target of rapamycin and AMP-activated protein kinase pathway proteins showed only time effects. mRNA expression of p53 increased after exercise (P = 0.005) and was higher in ED-LF at 3.5 h compared to EB-HF (P = 0.027). Plasma glucose and insulin area under the curve (P < 0.04) and peak values (P ≤ 0.05) were higher in EB-HF after the recovery drink. Achieving energy balance with a high-fat meal in a 'train-low' ('sleep-low') model did not enhance markers of skeletal muscle adaptation and impaired glycaemia in response to a recovery drink following training in the morning.

Contribution of oxygen extraction fraction to maximal oxygen uptake in healthy young men.

We analysed the importance of systemic and peripheral arteriovenous O2 difference ( a-v¯O2 difference and a-vf O2 difference, respectively) and O2 extraction fraction for maximal oxygen uptake ( V˙O2max ). Fick law of diffusion and the Piiper and Scheid model were applied to investigate whether diffusion versus perfusion limitations vary with V˙O2max . Articles (n = 17) publishing individual data (n = 154) on V˙O2max , maximal cardiac output ( Q˙max ; indicator-dilution or the Fick method), a-v¯O2 difference (catheters or the Fick equation) and systemic O2 extraction fraction were identified. For the peripheral responses, group-mean data (articles: n = 27; subjects: n = 234) on leg blood flow (LBF; thermodilution), a-vf O2 difference and O2 extraction fraction (arterial and femoral venous catheters) were obtained. Q˙max and two-LBF increased linearly by 4.9-6.0 L · min-1 per 1 L · min-1 increase in V˙O2max (R2  = .73 and R2  = .67, respectively; both P < .001). The a-v¯O2 difference increased from 118-168 mL · L-1 from a V˙O2max of 2-4.5 L · min-1 followed by a reduction (second-order polynomial: R2  = .27). After accounting for a hypoxemia-induced decrease in arterial O2 content with increasing V˙O2max (R2  = .17; P < .001), systemic O2 extraction fraction increased up to ~90% ( V˙O2max : 4.5 L · min-1 ) with no further change (exponential decay model: R2  = .42). Likewise, leg O2 extraction fraction increased with V˙O2max to approach a maximal value of ~90-95% (R2  = .83). Muscle O2 diffusing capacity and the equilibration index Y increased linearly with V˙O2max (R2  = .77 and R2  = .31, respectively; both P < .01), reflecting decreasing O2 diffusional limitations and accentuating O2 delivery limitations. In conclusion, although O2 delivery is the main limiting factor to V˙O2max , enhanced O2 extraction fraction (≥90%) contributes to the remarkably high V˙O2max in endurance-trained individuals.

Increased oxygen extraction and mitochondrial protein expression after small muscle mass endurance training.

When exercising with a small muscle mass, the mass-specific O2 delivery exceeds the muscle oxidative capacity resulting in a lower O2 extraction compared with whole-body exercise. We elevated the muscle oxidative capacity and tested its impact on O2 extraction during small muscle mass exercise. Nine individuals conducted six weeks of one-legged knee extension (1L-KE) endurance training. After training, the trained leg (TL) displayed 45% higher citrate synthase and COX-IV protein content in vastus lateralis and 15%-22% higher pulmonary oxygen uptake ( V ˙ O 2 peak ) and peak power output ( W ˙ peak ) during 1L-KE than the control leg (CON; all P < .05). Leg O2 extraction (catheters) and blood flow (ultrasound Doppler) were measured while both legs exercised simultaneously during 2L-KE at the same submaximal power outputs (real-time feedback-controlled). TL displayed higher O2 extraction than CON (main effect: 1.7 ± 1.6% points; P = .010; 40%-83% of W ˙ peak ) with the largest between-leg difference at 83% of W ˙ peak (O2 extraction: 3.2 ± 2.2% points; arteriovenous O2 difference: 7.1 ± 4.8 mL· L-1 ; P < .001). At 83% of W ˙ peak , muscle O2 conductance (DM O2 ; Fick law of diffusion) and the equilibration index Y were higher in TL (P < .01), indicating reduced diffusion limitations. The between-leg difference in O2 extraction correlated with the between-leg ratio of citrate synthase and COX-IV (r = .72-.73; P = .03), but not with the difference in the capillary-to-fiber ratio (P = .965). In conclusion, endurance training improves O2 extraction during small muscle mass exercise by elevating the muscle oxidative capacity and the recruitment of DM O2, especially evident during high-intensity exercise exploiting a larger fraction of the muscle oxidative capacity.