Beta-adrenergic blockade increases pulmonary vascular resistance and causes exaggerated hypoxic pulmonary vasoconstriction at high altitude: a physiological study.

BACKGROUND: An increasing number of hypertensive persons travel to high altitude while using antihypertensive medications such as betablockers. Nevertheless, while hypoxic exposure initiates an increase in pulmonary artery pressure (Ppa) and pulmonary vascular resistance (PVR), the contribution of the autonomic nervous system is unclear. In animals, ß-adrenergic blockade has induced pulmonary vasoconstriction in normoxia and exaggerated hypoxic pulmonary vasoconstriction (HPV) and both effects were abolished by muscarinic blockade. We thus hypothesized that in humans propranolol (PROP) increases Ppa and PVR in normoxia and exaggerates HPV, and that these effects of PROP are abolished by glycopyrrolate (GLYC). METHODS: In seven healthy male lowlanders, pulmonary artery pressure was invasively measured without medication, with PROP and PROP+GLYC, both at sea level (SL, 488m) and after a three-week sojourn at 3454m altitude (HA). Bilateral thigh-cuff release maneuvers were performed to derive pulmonary pressure-flow relationships and pulmonary vessel distensibility. RESULTS: At SL, PROP increased Ppa and PVR from (mean±SEM) 14±1 to 17±1mmHg and from 69±8 to 108±11dyn*s*cm-5 (21 and 57% increase, p=0.01 and p<0.0001). The PVR response to PROP was amplified at HA to 76% (p<0.0001, p[interaction]=0.05). At both altitudes, PROP+GLYC abolished the effect of PROP on Ppa and PVR. Pulmonary vessel distensibility decreased from 2.9±0.5 to 1.7±0.2 at HA (p<0.0001) and to 1.2±0.2 with PROP, and further decreased to 0.9±0.2%*mmHg-1 with PROP+GLYC (p=0.01). CONCLUSIONS: Our data show that ß-adrenergic blockade increases, and muscarinic blockade decreases PVR, whereas both increase pulmonary artery elastance. Future studies may confirm potential implications from the finding that ß-adrenergic blockade exaggerates HPV for the management of mountaineers using ß-blockers for prevention or treatment of cardiovascular conditions.

Yearly intrasubject variability of hematological biomarkers in elite athletes for the Athlete Biological Passport.

Confounding factors including exercise and environments challenge the interpretation of individual Athlete Biological Passports (ABPs). This study aimed to investigate the natural variability of hematological ABP parameters over 1 year in elite athletes compared with healthy control subjects and the validity of a multiparametric model estimating plasma volume (PV) shifts to correct individual ABP thresholds. Blood samples were collected monthly with full blood counts performed by flow cytometry (Sysmex XN analyzers) in 20 elite xc-skiers (ELITE) and 20 moderately trained controls. Individual ABP profiles were generated through Anti-Doping Administration & Management System Training, a standalone version of the ABP's adaptive model developed by the World Anti-Doping Agency. Additionally, eight serum parameters were computed as volume-sensitive biomarkers to run a multiparametric model to estimate PV. Variability in ELITE compared with controls was significantly higher for the Abnormal Blood Profile Scores (P = 0.003). Among 12 Atypical Passport Findings (ATPF) initially reported, six could be removed after correction of PV shifts with the multiparametric modeling. However, several ATPF were additionally generated (n = 19). Our study outlines a larger intraindividual variability in elite athletes, likely explained by more frequent exposure to extrinsic factors altering hematological biomarkers. PV correction for individual ABP thresholds allowed to explain most of the atypical findings while generating multiple new ATPF occurrences in the elite population. Overall, accounting for PV shifts in elite athletes was shown to be paramount in this study outlining the opportunity to consider PV variations with novel approaches when interpreting individual ABP profiles.

Skeletal muscle mitochondria demonstrate similar respiration per cristae surface area independent of training status and sex in healthy humans.

The impact of training status and sex on intrinsic skeletal muscle mitochondrial respiratory capacity remains unclear. We examined this by analysing human skeletal muscle mitochondrial respiration relative to mitochondrial volume and cristae density across training statuses and sexes. Mitochondrial cristae density was estimated in skeletal muscle biopsies originating from previous independent studies. Participants included females (n = 12) and males (n = 41) across training statuses ranging from untrained (UT, n = 8), recreationally active (RA, n = 9), active-to-elite runners (RUN, n = 27) and cross-country skiers (XC, n = 9). The XC and RUN groups demonstrated higher mitochondrial volume density than the RA and UT groups while all active groups (RA, RUN and XC) displayed higher mass-specific capacity of oxidative phosphorylation (OXPHOS) and mitochondrial cristae density than UT. Differences in OXPHOS diminished between active groups and UT when normalising to mitochondrial volume density and were lost when normalising to muscle cristae surface area density. Moreover, active females (n = 6-9) and males (n = 15-18) did not differ in mitochondrial volume and cristae density, OXPHOS, or when normalising OXPHOS to mitochondrial volume density and muscle cristae surface area density. These findings demonstrate: (1) differences in OXPHOS between active and untrained individuals may be explained by both higher mitochondrial volume and cristae density in active individuals, with no difference in intrinsic mitochondrial respiratory capacity (OXPHOS per muscle cristae surface area density); and (2) no sex differences in mitochondrial volume and cristae density or mass-specific and normalised OXPHOS. This highlights the importance of normalising OXPHOS to muscle cristae surface area density when studying skeletal muscle mitochondrial biology. KEY POINTS: Oxidative phosphorylation is the mitochondrial process by which ATP is produced, governed by the electrochemical gradient across the inner mitochondrial membrane with infoldings named cristae. In human skeletal muscle, the mass-specific capacity of oxidative phosphorylation (OXPHOS) can change independently of shifts in mitochondrial volume density, which may be attributed to variations in cristae density. We demonstrate that differences in skeletal muscle OXPHOS between healthy females and males, ranging from untrained to elite endurance athletes, are matched by differences in cristae density. This suggests that higher OXPHOS in skeletal muscles of active individuals is attributable to an increase in the density of cristae. These findings broaden our understanding of the variability in human skeletal muscle OXPHOS and highlight the significance of cristae, specific to mitochondrial respiration.

Eight weeks of heavy strength training increases hemoglobin mass and V̇o2peak in well-trained to elite female and male rowers.

O2-transport and endurance exercise performance are greatly influenced by hemoglobin mass (Hbmass), which largely depends on lean body mass (LBM). This study investigated the effects of 8 wk with three weekly sessions of conventional (3-SET: 3 × 10 reps) or high-volume strength training (10-SET: 5-10 × 10 reps) on LBM, Hbmass, muscle strength, and exercise performance in female and male rowers. Hematological parameters were obtained through CO rebreathing and body composition by dual-energy X-ray absorptiometry (DEXA) scans before and after the training period. Concomitantly, V̇o2peak was determined during 2-km ergometer rowing and muscle strength by isometric midthigh pull. There were no differences in training responses between groups for any of the parameters. Pooled data revealed overall increments for Hbmass (10-SET: 882 ± 199 g to 897 ± 213 g; 3-SET: 936 ± 245 g to 962 ± 247 g, P = 0.02) and V̇o2peak (10-SET: 4.3 ± 1.0 to 4.4 ± 0.9 L·min-1; 3-SET: 4.5 ± 0.9 to 4.6 ± 0.9 L·min-1, P = 0.03), whereas LBM remained unchanged (10-SET: 58.7 ± 10.5 to 58.7 ± 10.1 kg; 3-SET: 64.1 ± 10.8 to 64.5 ± 10.6 kg, P = 0.42). Maximal isometric midthigh pull strength increased (10-SET: 224 ± 47 kg to 237 ± 55 kg; 3-SET: 256 ± 77 kg to 281 ± 83 kg, P = 0.001). Strong associations were observed between LBM and Hbmass and V̇o2peak (r2 = 0.88-0.90), entailing sex differences in Hbmass and V̇o2peak. Normalizing V̇o2peak to LBM reduced the sex difference to ∼10%, aligning with the sex difference in Hbmass·LBM-1. Strength training successfully increased Hbmass and V̇o2peak in elite female and male rowers, without an additional effect from increased training volume. Moreover, sex differences in V̇o2peak were mainly explained by differences in LBM, but likely also by differences in Hbmass·LBM-1.NEW & NOTEWORTHY This study in female and male rowers demonstrates that hemoglobin mass (Hbmass), V̇o2peak, and muscle strength increases with 8 wk of heavy strength training and that this response is not different between conventional (3 × 10 repetitions) and high-volume strength training (10 × 10 repetitions). Moreover, female rowers exhibited less hemoglobin per kilogram of lean body mass compared with their male counterparts, which likely contributes to sex differences in V̇o2peak and rowing performance.

Intravascular volumes and the influence on anemia assessed by a carbon monoxide rebreathing method in patients undergoing maintenance hemodialysis.

INTRODUCTION: Fluid overload is a major challenge in hemodialysis patients and might cause hypervolemia. We speculated that hemodialysis patients reaching dry weight could have undetected hypervolemia and low hemoglobin (Hb) concentration (g/dL) due to hemodilution. METHODS: The study included hemodialysis patients (n = 22) and matched healthy controls (n = 22). Blood volume, plasma volume, red blood cell volume, and total Hb mass were determined using a carbon monoxide (CO)-rebreathing method in hemodialysis patients reaching dry weight and controls. Blood volume measurements were also obtained by a dual-isotope labeling technique in a subgroup for validation purposes. FINDINGS: In the hemodialysis group, the median specific blood volume was 89.3 mL/kg (interquartile range [IQR]: 76.7-95.4 mL/kg) and was higher than in the control group (79.9 mL/kg [IQR: 70.4-88.0 mL/kg]; p < 0.037). The median specific plasma volume was 54.7 mL/kg (IQR: 47.1-61.0 mL/kg) and 44.0 mL/kg (IQR: 38.7-49.5 mL/kg) in the hemodialysis and control groups, respectively (p < 0.001). Hb concentration was lower in hemodialysis patients (p < 0.001), whereas no difference in total Hb mass was observed between groups (p = 0.11). A correlation was found between blood volume measured by the CO-rebreathing test and the dual-isotope labeling technique in the control group (r = 0.83, p = 0.015), but not the hemodialysis group (r = 0.25, p = 0.60). DISCUSSION: The hemodialysis group had increased specific blood volume at dry weight due to high plasma volume, suggesting a hypervolemic state. However, correlation was not established against the dual-isotope labeling technique underlining that the precision of the CO-rebreathing test should be further validated. The total Hb mass was similar between hemodialysis patients and controls, unlike Hb concentration, which emphasizes that Hb concentration is an inaccurate marker of anemia among hemodialysis patients.

Techniques to Assess the Effect of Sodium-Glucose Cotransporter 2 Inhibitors on Blood Volume in Patients with Diabetic Kidney Disease.

BACKGROUND: Sodium-glucose cotransporter 2 (SGLT2) inhibitors exert a kidney protective effect in patients with diabetic kidney disease. Several mechanisms have been proposed, but why precisely SGLT2 inhibition has a kidney protective effect is incompletely understood. Clinical trials using SGLT2 inhibitors have found them to induce a rapid weight loss likely due to loss of sodium and subsequently fluid. While SGLT2 inhibitors are reported to increase hematocrit, it remains unknown whether the natriuretic and aquaretic effect reduces patient's blood volume and whether this could partly explain its kidney protective effects. A blood volume reduction could induce several beneficial effects with reduction in arterial and venous blood pressure as two central mechanisms. The aim of this paper was to review current techniques for assessing patient blood volume that could enhance our understanding of SGLT2 inhibitors' physiological effects. SUMMARY: Changes induced by SGLT2 inhibitors on erythrocyte volume and plasma volume can be assessed by tracer dilution techniques that include radioisotopes, indocyanine green (ICG) dye, or carbon monoxide (CO). Techniques with radioisotopes can provide direct estimates of both erythrocyte volume and plasma volume but are cumbersome procedures and the radiation exposure is a limitation for repeated measures in clinical studies. Methods more suitable for repeated assessment of erythrocyte and plasma volume include dilution of injected ICG dye or dilution of inhaled CO. ICG dye requires higher precision with timed blood samples and provides only a direct estimate of plasma volume wherefrom erythrocyte volume is estimated. Inhalation of CO is a time-effective and automated method that provides measure of the total hemoglobin mass wherefrom erythrocyte and plasma volumes are estimated. KEY MESSAGES: A kidney protective effect has been observed in clinical trials with SGLT2 inhibitors, but the underlying mechanisms are not fully understood. Significant weight loss within weeks has been reported in the SGLT2 inhibitor trials and could be related to a reduction in blood volume secondary to increased natriuresis and aquaresis. Alterations in blood volume compartments can be quantified by tracer dilution techniques and further improve our understanding of kidney protection from SGLT2 inhibitors.

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.

Validation of a clinically applicable device for fast and accurate quantification of blood volume.

INTRODUCTION: Determination of blood volume (BV) using the dual-isotope (e.g., 99m Tc-labeled red blood cells [99m Tc-RBC] and 125 I-labeled human serum albumin [125 I-HSA]) injection method is limited in medicine due to the long isotope half-life. However, BV has been determined in laboratory settings for 100 years using the carbon monoxide (CO)-rebreathing-based procedure, which allows frequent BV measurements. METHODS: We investigated the reliability and accuracy of a semi-automated CO-rebreathing device by comparing it against the dual-isotope methodology and its ability to detect a known blood removal. In study A, BV was determined three times in ~2 h; twice using the device with rebreathing protocols lasting 2 (CO2min ) and 10 min (CO10min ) and once with the dual-isotope technique. In study B, the accuracy of the device was assessed by its ability to detect a 2% removal of BV. RESULTS: A good correlation was observed between both the CO-rebreathing protocols (r2 = 0.89-0.98; p < 0.001) and the dual-isotope approach (r2 = 0.89-0.95; p < 0.001). In absolute terms BV was 425 ± 263 mL and 491 ± 388 mL lower (p < 0.001) when quantified with the dual-isotope compared to the CO-rebreathing protocols. When reducing BV by 132 ± 25 mL (2%), the device quantified a lower (p < 0.001) BV of 150 ± 45 mL. CONCLUSION: This study emphasizes that the semi-automated device accurately determines small changes (i.e., 2%) in BV and that a high correlation with the dual-isotope methodology exists. The findings are clinically relevant owing to the method's simple and fast nature (the absence of radioactive tracers and reduced time requirements, i.e., ~15 min vs. ~180 min) and the possibility for repeated measurements within a single day.

Hematological, skeletal muscle fiber, and exercise performance adaptations to heat training in elite female and male cyclists.

Heat exercise training may increase exercise performance in athletes. The underlying mechanisms remain partly unresolved, and it is unknown if female and male athletes may experience comparable gains. The aims were to investigate whether heat training (HEAT) increases hemoglobin mass (Hbmass), skeletal muscle fiber characteristics, and thermoneutral exercise performance in elite female and male endurance athletes. Female (n = 20; V̇o2max = 58.2 ± 6.7 mL·min-1·kg-1) and male (n = 27; V̇o2max = 76.4 ± 7.8 mL·min-1·kg-1) cyclists were studied before and after 5 wk of randomized control or HEAT consisting of five weekly sessions each of 50 min duration, which were included in their normal training regimes. Overall, the observed relative responses to HEAT were largely similar in female and male study participants. HEAT increased (P < 0.05) Hbmass in females from 650 ± 77 to 675 ± 76 g (4.0 ± 1.6%) and from 1,008 ± 155 to 1,041 ± 147 g (3.5 ± 2.3%) in males. In contrast, skeletal muscle citrate synthase activity, fiber type distribution, and capillary density remained unchanged with HEAT. Lactate threshold, V̇o2max, and mean power output during 15-min all-out testing were all enhanced (P < 0.05) following HEAT in female and male study participants. In conclusion, 5 wk of HEAT increases Hbmass in female and male elite cyclists and improves exercise performance in a thermoneutral environment. Based on this, heat training may be recommended to elite female and male athletes aiming to perform in a thermoneutral environment.NEW & NOTEWORTHY We demonstrate in elite female and male cyclists that heat exercise training (5 × 50 min sessions/wk for 5 wk) facilities Hbmass and other hematological parameters more than control exercise training, whereas skeletal muscle properties remain unaltered. Collectively, this coincided with improvements in lactate threshold, V̇o2max, and 15-min all-out cycling performance.

Increased blood reactive oxygen species and hepcidin in obstructive sleep apnea precludes expected erythrocytosis.

Obstructive sleep apnea (OSA) causes intermittent hypoxia during sleep. Hypoxia predictably initiates an increase in the blood hemoglobin concentration (Hb); yet in our analysis of 527 patients with OSA, >98% did not have an elevated Hb. To understand why patients with OSA do not develop secondary erythrocytosis due to intermittent hypoxia, we first hypothesized that erythrocytosis occurs in these patients, but is masked by a concomitant increase in plasma volume. However, we excluded that explanation by finding that the red cell mass was normal (measured by radionuclide labeling of erythrocytes and carbon monoxide inhalation). We next studied 45 patients with OSA before and after applying continuous positive airway pressure (CPAP). We found accelerated erythropoiesis in these patients (increased erythropoietin and reticulocytosis), but it was offset by neocytolysis (lysis of erythrocytes newly generated in hypoxia upon return to normoxia). Parameters of neocytolysis included increased reactive oxygen species from expanded reticulocytes' mitochondria. The antioxidant catalase was also downregulated in these cells from hypoxia-stimulated microRNA-21. In addition, inflammation-induced hepcidin limited iron availability for erythropoiesis. After CPAP, some of these intermediaries diminished but Hb did not change. We conclude that in OSA, the absence of significant increase in red cell mass is integral to the pathogenesis, and results from hemolysis via neocytolysis combined with inflammation-mediated suppression of erythropoiesis.

Lowered muscle glycogen reduces body mass with no effect on short-term exercise performance in men.

Performance in short-duration sports is highly dependent on muscle glycogen, but the total degradation is only moderate and considering the water-binding property of glycogen, unnecessary storing of glycogen may cause an unfavorable increase in body mass. To investigate this, we determined the effect of manipulating dietary carbohydrates (CHO) on muscle glycogen content, body mass, and short-term exercise performance. In a randomized and counterbalanced cross-over design, twenty-two men completed two maximal cycle tests of either 1-min (n = 10) or 15-min (n = 12) duration with different pre-exercise muscle glycogen levels. Glycogen manipulation was initiated three days prior to the tests by exercise-induced glycogen depletion followed by ingestion of a moderate (M-CHO) or high (H-CHO) CHO-diet. Subjects were weighed before each test, and muscle glycogen content was determined in biopsies from m. vastus lateralis before and after each test. Pre-exercise muscle glycogen content was lower following M-CHO than H-CHO (367 mmol · kg-1 DW vs. 525 mmol · kg-1 DW, p < 0.00001), accompanied by a 0.7 kg lower body mass (p < 0.00001). No differences were observed in performance between diets in neither the 1-min (p = 0.33) nor the 15-min (p = 0.99) test. In conclusion, pre-exercise muscle glycogen content and body mass were lower after ingesting moderate compared with high amounts of CHO, while short-term exercise performance was unaffected. This demonstrates that adjusting pre-exercise glycogen levels to the requirements of competition may provide an attractive weight management strategy in weight-bearing sports, particularly in athletes with high resting glycogen levels.

High or hot-Perspectives on altitude camps and heat-acclimation training as preparation for prolonged stage races.

Adaptation to heat stress and hypoxia are relevant for athletes participating in Tour de France or similar cycling races taking place during the summertime in landscapes with varying altitude. Both to minimize detrimental performance effects associated with arterial desaturation occurring at moderate altitudes in elite athletes, respectively, reduce the risk of hyperthermia on hot days, but also as a pre-competition acclimatization strategy to boost blood volume in already highly adapted athletes. The hematological adaptations require weeks of exposure to manifest, but are attractive as an augmented hemoglobin mass may improve arterial oxygen delivery and hence benefit prolonged performances. Altitude training camps have in this context a long history in exercise physiology and are still common practice in elite cycling. However, heat-acclimation training provides an attractive alternative for some athletes either as a stand-alone approach or in combination with altitude. The present paper provides an update and practical perspectives on the potential to utilize hypoxia and heat exposure to optimize hematological adaptations. Furthermore, we will consider temporal aspects both in terms of onset and decay of the adaptations relevant for improved thermoregulatory capacity and respiratory adaptations to abate arterial desaturation during altitude exposure. From focus on involved physiological mechanisms, time course, and responsiveness in elite athletes, we will provide guidance based on our experience from practical implementation in cyclists preparing for prolonged stage races such as the Tour de France.

Heat Training Efficiently Increases and Maintains Hemoglobin Mass and Temperate Endurance Performance in Elite Cyclists.

PURPOSE AND METHODS: To test whether heat training performed as 5 × 50-min sessions per week for 5 wk in a heat chamber (CHAMBER) or while wearing a heat suit (SUIT), in temperate conditions, increases hemoglobin mass (Hb mass ) and endurance performance in elite cyclists, compared with a control group (CON-1). Furthermore, after the 5-wk intervention, we tested whether three sessions per week for 3 wk with heat suit (SUIT main ) would maintain Hb mass elevated compared with athletes who returned to normal training (HEAT stop ) or who continued to be the control group (CON-2). RESULTS: During the initial 5 wk, SUIT and CHAMBER increased Hb mass (2.6% and 2.4%) to a greater extent than CON-1 (-0.7%; both P < 0.01). The power output at 4 mmol·L -1 blood lactate and 1-min power output ( Wmax ) improved more in SUIT (3.6% and 7.3%, respectively) than CON-1 (-0.6%, P < 0.05; 0.2%, P < 0.01), whereas this was not the case for CHAMBER (1.4%, P = 0.24; 3.4%, P = 0.29). However, when SUIT and CHAMBER were pooled this revealed a greater improvement in a performance index (composed of power output at 4 mmol·L -1 blood lactate, Wmax , and 15-min power output) than CON-1 (4.9% ± 3.2% vs 1.7% ± 1.1%, respectively; P < 0.05). During the 3-wk maintenance period, SUIT main induced a larger increase in Hb mass than HEAT stop (3.3% vs 0.8%; P < 0.05), which was not different from the control (CON-2; 1.6%; P = 0.19), with no differences between HEAT stop and CON-2 ( P = 0.52). CONCLUSIONS: Both SUIT and CHAMBER can increase Hb mass , and pooling SUIT and CHAMBER demonstrates that heat training can increase performance. Furthermore, compared with cessation of heat training, a sustained increase in Hb mass was observed during a subsequent 3-wk maintenance period, although the number of weekly heat training sessions was reduced to 3.

Heat suit training increases hemoglobin mass in elite cross-country skiers.

PURPOSE: The primary purpose was to test the effect of heat suit training on hemoglobin mass (Hbmass ) in elite cross-country (XC) skiers. METHODS: Twenty-five male XC-skiers were divided into a group that added 5 × 50 min weekly heat suit training sessions to their regular training (HEAT; n = 13, 23 ± 5 years, 73.9 ± 5.2 kg, 180 ± 6 cm, 76.8 ± 4.6 ml·min-1 ·kg-1 ) or to a control group matched for training volume and intensity distribution (CON; n = 12, 23 ± 4 years, 78.4 ± 5.8 kg, 184 ± 4 cm, 75.2 ± 3.4 ml·min-1 ·kg-1 ) during the five-week intervention period. Hbmass , endurance performance and factors determining endurance performance were assessed before and after the intervention. RESULTS: HEAT led to 30 g greater Hbmass (95% CI: [8.5, 51.7], p = 0.009) and 157 ml greater red blood cell volume ([29, 285], p = 0.018) post-intervention, compared to CON when adjusted for baseline values. In contrast, no group differences were observed for changes in work economy, running velocity, and fractional utilization of maximal oxygen uptake (V̇O2max ) at 4 mmol·L-1 blood lactate, V̇O2max or 15-min running distance performance trial during the intervention. CONCLUSION: HEAT induced a larger increase in Hbmass and red blood cell volume after five weeks with five weekly heat suit training sessions than CON, but with no detectable group differences on physiological determinants of endurance performance or actual endurance performance in elite CX skiers.

Dichotomous Responses to Chronic Fetal Hypoxia Lead to a Predetermined Aging Phenotype.

Hypoxia-induced intrauterine growth restriction increases the risk for cardiovascular, renal, and other chronic diseases in adults, representing thus a major public health problem. Still, not much is known about the fetal mechanisms that predispose these individuals to disease. Using a previously validated mouse model of fetal hypoxia and bottom-up proteomics, we characterize the response of the fetal kidney to chronic hypoxic stress. Fetal kidneys exhibit a dichotomous response to chronic hypoxia, comprising on the one hand cellular adaptations that promote survival (glycolysis, autophagy, and reduced DNA and protein synthesis), but on the other processes that induce a senescence-like phenotype (infiltration of inflammatory cells, DNA damage, and reduced proliferation). Importantly, chronic hypoxia also reduces the expression of the antiaging proteins klotho and Sirt6, a mechanism that is evolutionary conserved between mice and humans. Taken together, we uncover that predetermined aging during fetal development is a key event in chronic hypoxia, establishing a solid foundation for Barker's hypothesis of fetal programming of adult diseases. This phenotype is associated with a characteristic biomarker profile in tissue and serum samples, exploitable for detecting and targeting accelerated aging in chronic hypoxic human diseases.

Case Report: Heat Suit Training May Increase Hemoglobin Mass in Elite Athletes.

PURPOSE: The present case report aimed to investigate the effects of exercise training in temperate ambient conditions while wearing a heat suit on hemoglobin mass (Hbmass). METHODS: As part of their training regimens, 5 national-team members of endurance sports (3 males) performed ∼5 weekly heat suit exercise training sessions each lasting 50 minutes for a duration of ∼8 weeks. Two other male athletes acted as controls. After the initial 8-week period, 3 of the athletes continued for 2 to 4 months with ∼3 weekly heat sessions in an attempt to maintain acquired adaptations at a lower cost. Hbmass was assessed in duplicate before and after intervention and maintenance period based on automated carbon monoxide rebreathing. RESULTS: Heat suit exercise training increased rectal temperature to a median value of 38.7°C (range 38.6°C-39.0°C), and during the initial ∼8 weeks of heat suit training, there was a median increase of 5% (range 1.4%-12.9%) in Hbmass, while the changes in the 2 control athletes were a decrease of 1.7% and an increase of 3.2%, respectively. Furthermore, during the maintenance period, the 3 athletes who continued with a reduced number of heat suit sessions experienced a change of 0.7%, 2.8%, and -1.1%, indicating that it is possible to maintain initial increases in Hbmass despite reducing the weekly number of heat suit sessions. CONCLUSIONS: The present case report illustrates that heat suit exercise training acutely raises rectal temperature and that following 8 weeks of such training Hbmass may increase in elite endurance athletes.

Cerebral lactate uptake during exercise is driven by the increased arterial lactate concentration.

Exercise facilitates cerebral lactate uptake, likely by increasing arterial lactate concentration and hence the diffusion gradient across the blood-brain barrier. However, nonspecific ß-adrenergic blockade by propranolol has previously reduced the arterio-jugular venous lactate difference (AVLac) during exercise, suggesting ß-adrenergic control of cerebral lactate uptake. Alternatively, we hypothesized that propranolol reduces cerebral lactate uptake by decreasing arterial lactate concentration. To test that hypothesis, we evaluated cerebral lactate uptake taking changes in arterial concentration into account. Nine healthy males performed incremental cycling exercises to exhaustion with and without intravenous propranolol (18.7 ± 1.9 mg). Lactate concentration was determined in arterial and internal jugular venous blood at the end of each workload. To take changes in arterial lactate into account, we calculated the fractional extraction (FELac) defined as AVLac divided by the arterial lactate concentration. Arterial lactate concentration was reduced by propranolol at any workload (P < 0.05), reaching 14 ± 3 and 11 ± 3 mmol·l-1 during maximal exercise without and with propranolol, respectively. Although AVLac and FELac increased during exercise (both P < 0.05), they were both unaffected by propranolol at any workload (P = 0.68 and P = 0.26) or for any given arterial lactate concentration (P = 0.78 and P = 0.22). These findings support that while propranolol may reduce cerebral lactate uptake, this effect reflects the propranolol-induced reduction in arterial lactate concentration and not inhibition of a ß-adrenergic mechanism within the brain. We hence conclude that cerebral lactate uptake during exercise is directly driven by the increasing arterial concentration with work rate.NEW & NOTEWORTHY During exercise the brain consumes lactate as a substitute for glucose. Propranolol has previously attenuated this cerebral lactate uptake, suggesting a ß-adrenergic transport mechanism. However, in the present study, we demonstrate that the fractional extraction of arterial lactate by the brain is unaffected by propranolol throughout incremental exercise to exhaustion. We conclude that cerebral lactate uptake during exercise is passively driven by the increasing arterial concentration, rather than by a ß-adrenergic mechanism within the brain.

Training wearing thermal clothing and training in hot ambient conditions are equally effective methods of heat acclimation.

The objective was to compare the efficacy of three different heat acclimation protocols to improve exercise performance in the heat. Thirty four cyclists completed one of three 10-day interventions 1) 50-min cycling per day in 35 °C, 2) 50-min cycling per day wearing thermal clothing, and 3) 50-min cycling wearing thermal clothing plus 25 min hot water immersion per day. Pre- and post-intervention hemoglobin mass, intravascular volumes and core temperature were determined at rest. Heart rate, sweat rate, blood lactate concentration and core temperature were evaluated during 15-min submaximal and 30-min all-out cycling performance conducted in 35.2 ±â€¯0.1 °C and 61 ±â€¯1% relative humidity. There were no significant between-group differences in any of the determined variables. None of the interventions statistically altered any of the parameters investigated as part of the 15-min submaximal trial. However, following the intervention period, heat chamber, thermal clothing and thermal clothing + hot water immersion all improved 30-min all-out average power in the heat (9.5 ±â€¯3.8%, 9.5 ±â€¯3.6 and 9.9 ±â€¯5.2%, respectively, p < 0.001, F = 192.3). At termination of the 30-min all-out test, the increase in blood lactate concentration, rate of perceived exertion and sweat rate were not different between the three interventions. In conclusion, daily training sessions conducted either in ambient 35 °C, while wearing thermal clothing in temperate conditions or while wearing thermal clothing combined with hot water immersion are equally effective for improving exercise performance in the heat.