The erythroid terminal differentiation program couples sequential cell divisions with progressive reductions in cell size. The erythropoietin receptor (EpoR) is essential for erythroblast survival, ...but its other functions are not well characterized. Here we use Epor
mouse erythroblasts endowed with survival signaling to identify novel non-redundant EpoR functions. We find that, paradoxically, EpoR signaling increases red cell size while also increasing the number and speed of erythroblast cell cycles. EpoR-regulation of cell size is independent of established red cell size regulation by iron. High erythropoietin (Epo) increases red cell size in wild-type mice and in human volunteers. The increase in mean corpuscular volume (MCV) outlasts the duration of Epo treatment and is not the result of increased reticulocyte number. Our work shows that EpoR signaling alters the relationship between cycling and cell size. Further, diagnostic interpretations of increased MCV should now include high Epo levels and hypoxic stress.
Sprint-interval training (SIT) is efficient at improving maximal aerobic capacity and anaerobic fitness at sea-level and may be a feasible training strategy at altitude. Here, it was evaluated if SIT ...intensity can be maintained in mild to moderate hypoxia. It was hypothesized that 6 x 30 s Wingate sprint performance with 2 min active rest between sprints can be performed in hypoxic conditions corresponding to ~3,000 m of altitude without reducing mean power output (MPO). In a single-blinded, randomized crossover design, ten highly-trained male endurance athletes with a maximal oxygen uptake (Formula: see textO2max) of 68 ± 5 mL O2 × min-1 × kg-1 completed 6 x 30 s all-out Wingate cycling sprints separated by two-minute active recovery on four separate days in a hypobaric chamber. The ambient pressure within the chamber on each experimental day was 772 mmHg (~0 m), 679 mmHg (~915 m), 585 mmHg (~ 2,150 m), and 522 mmHg (~3,050 m), respectively. MPO was not different at sea-level and up to ~2,150 m (~1% and ~3% non-significant decrements at ~915 and ~2,150 m, respectively), whereas MPO was ~5% lower (P<0.05) at ~3,050 m. Temporal differences between altitudes was not different for peak power output (PPO), despite a main effect of altitude. In conclusion, repeated Wingate exercise can be completed by highly-trained athletes at altitudes up to ~2,150 m without compromising MPO or PPO. In contrast, MPO was compromised in hypobaric hypoxia corresponding to ~3,050 m. Thus, SIT may be an efficient strategy for athletes sojourning to moderate altitude and aiming to maintain training quality.
The SHFT device is a novel running wearable consisting of two pods connected to your smartphone issuing several running metrics based on accelerometer and gyroscope technology. The purpose of this ...study was to investigate the reliability and validity of the power output (PO) metric produced by the SHFT device. To assess reliability, 12 men ran on an outdoor track at 10.5 km·h−1 and 12 km·h−1 on two consecutive days. To assess validity, oxygen uptake (VO2) and SHFT data from eight men and seven women were collected during incremental submaximal running tests on an indoor treadmill on one to four separate days (34 tests in total). SHFT reliability on the outdoor track was strong with coefficients of variance (CV) of 1.8% and 2.4% for 10.5 and 12 km·h−1, respectively. We observed a very strong linear relationship between PO and VO2 (r2 = 0.54) within subjects, and a very strong linear relationship within each subject within each treadmill test (r2 = 0.80). We conclude that SHFT provides a reliable running power estimate and that a very strong relationship between SHFT-Power and metabolic rate exists, which places SHFT as one of the leading commercially available running power meters.
Detailed physiological phenotyping was hypothesized to have predictive value for Olympic distance cross-country mountain bike (XCO-MTB) performance. Additionally, mean (MPO) and peak power output ...(PPO) in 4 × 30 s all-out sprinting separated by 1 min was hypothesized as a simple measure with predictive value for XCO-MTB performance. Parameters indicative of body composition, cardiovascular function, power and strength were determined and related to XCO-MTB national championship performance (n = 11). Multiple linear regression demonstrated 98% of the variance (P < 0.001) in XCO-MTB performance (t
XCO-MTB
; min) is explained by maximal oxygen uptake relative to body mass (VO
2peak,rel
; ml/kg/min), 30 s all-out fatigue resistance (FI; %) and with a minor contribution from quadriceps femoris maximal torque (T
max
; Nm): t
XCO-MTB
= −0.217× VO
2peak,rel.
-0.201× FI+ 0.012× T
max
+ 85.4. Parameters with no additional predictive value included hemoglobin mass, leg peak blood flow, femoral artery diameter, knee-extensor peak workload, jump height, quadriceps femoris maximal voluntary contraction force and rate of force development. Additionally, multiple linear regression demonstrated parameters obtained from 4x30s repeated sprinting explained 88% of XCO-MTB variance (P < 0.001) with t
XCO-MTB
= −5.7× MPO+ 5.0× PPO+ 55.9. In conclusion, XCO-MTB performance is predictable from VO
2peak,rel
and 30 s all-out fatigue resistance. Additionally, power variables from a repeated sprint test provides a cost-effective way of monitoring athletes XCO-MTB performance.
The performance of elite breath hold divers (BHD) includes static breath hold for more than 11 minutes, swimming as far as 300 m, or going below 250 m in depth, all on a single breath of air. Diving ...mammals are adapted to sustain oxidative metabolism in hypoxic conditions through several metabolic adaptations, including improved capacity for oxygen transport and mitochondrial oxidative phosphorylation in skeletal muscle. It was hypothesized that similar adaptations characterized human BHD. Hence, the purpose of this study was to examine the capacity for oxidative metabolism in skeletal muscle of BHD compared to matched controls.
Biopsies were obtained from the lateral vastus of the femoral muscle from 8 Danish BHD and 8 non-diving controls (Judo athletes) matched for morphometry and whole body VO2max. High resolution respirometry was used to determine mitochondrial respiratory capacity and leak respiration with simultaneous measurement of mitochondrial H2O2 emission. Maximal citrate synthase (CS) and 3-hydroxyacyl CoA dehydrogenase (HAD) activity were measured in muscle tissue homogenates. Western Blotting was used to determine protein contents of respiratory complex I-V subunits and myoglobin in muscle tissue lysates.
Muscle biopsies of BHD revealed lower mitochondrial leak respiration and electron transfer system (ETS) capacity and higher H2O2 emission during leak respiration than controls, with no differences in enzyme activities (CS and HAD) or protein content of mitochondrial complex subunits myoglobin, myosin heavy chain isoforms, markers of glucose metabolism and antioxidant enzymes.
We demonstrated for the first time in humans, that the skeletal muscles of BHD are characterized by lower mitochondrial oxygen consumption both during low leak and high (ETS) respiration than matched controls. This supports previous observations of diving mammals demonstrating a lower aerobic mitochondrial capacity of the skeletal muscles as an oxygen conserving adaptation during prolonged dives.
The cardiac electrical conduction system is very sensitive to hypoglycemia and hypoxia, and the consequence may be brady-arrythmias. Weddell seals endure brady-arrythmias during their dives when ...desaturating to 3.2 kPa and elite breath-hold-divers (BHD), who share metabolic and cardiovascular adaptions including bradycardia with diving mammals, endure similar desaturation during maximum apnea. We hypothesized that hypoxia causes brady-arrythmias during maximum apnea in elite BHD. Hence, this study aimed to define the arterial blood glucose (Glu), peripheral saturation (SAT), heart rhythm (HR), and mean arterial blood pressure (MAP) of elite BHD during maximum apneas.
HR was monitored with Direct-Current-Pads/ECG-lead-II and MAP and Glu from a radial arterial-catheter in nine BHD performing an immersed and head-down maximal static pool apnea after three warm-up apneas. SAT was monitored with a sensor on the neck of the subjects. On a separate day, a 12-lead-ECG-monitored maximum static apnea was repeated dry (
= 6).
During pool apnea of maximum duration (385 ± 70 s), SAT decreased from 99.6 ± 0.5 to 58.5 ± 5.5% (∼PaO
4.8 ± 1.5 kPa,
< 0.001), while Glu increased from 5.8 ± 0.2 to 6.2 ± 0.2 mmol/l (
= 0.009). MAP increased from 103 ± 4 to 155 ± 6 mm Hg (
< 0.005). HR decreased to 46 ± 10 from 86 ± 14 beats/minute (
< 0.001). HR and MAP were unchanged after 3-4 min of apnea. During dry apnea (378 ± 31 s), HR decreased from 55 ± 4 to 40 ± 3 beats/minute (
= 0.031). Atrioventricular dissociation and junctional rhythm were observed both during pool and dry apneas.
Our findings contrast with previous studies concluding that Glu decreases during apnea diving. We conclude during maximum apnea in elite BHD that (1) the diving reflex is maximized after 3-4 min, (2) increasing Glu may indicate lactate metabolism in accordance with our previous results, and (3) extreme hypoxia rather than hypoglycemia causes brady-arrythmias in elite BHD similar to diving mammals.
This review critically evaluates the magnitude of performance enhancement that can be expected from various autologous blood transfusion (ABT) procedures and the underlying physiological mechanisms. ...The review is based on a systematic search, and it was reported that 4 of 28 studies can be considered of very high quality, i.e. placebo-controlled, double-blind crossover studies. However, both high-quality studies and other studies have generally reported performance-enhancing effects of ABT on exercise intensities ranging from ~70 to 100% of absolute peak oxygen uptake (VO
2peak
) with durations of 5–45 min, and the effect was also seen in well-trained athletes. A linear relationship exists between ABT volume and change in VO
2peak
. The likely correlation between ABT volume and endurance performance was not evident in the few available studies, but reinfusion of as little as 135 mL packed red blood cells has been shown to increase time trial performance. Red blood cell reinfusion increases endurance performance by elevating arterial oxygen content (C
a
O
2
). The increased C
a
O
2
is accompanied by reduced lactate concentrations at submaximal intensities as well as increased VO
2peak
. Both effects improve endurance performance. Apparently, the magnitude of change in haemoglobin concentration (Hb) explains the increase in VO
2peak
associated with ABT because blood volume and maximal cardiac output have remained constant in the majority of ABT studies. Thus, the arterial-venous O
2
difference during exercise must be increased after reinfusion, which is supported by experimental evidence. Additionally, it remains a possibility that ABT can enhance repeated sprint performance, but studies on this topic are lacking. The only available study did not reveal a performance-enhancing effect of reinfusion on 4 × 30 s sprinting. The reviewed studies are of importance for both the physiological understanding of how ABT interacts with exercise capacity and in relation to anti-doping efforts. From an anti-doping perspective, the literature review demonstrates the need for methods to detect even small ABT volumes.
Angiotensin‐converting enzyme (ACE) activity may be one determinant of adaptability to exercise training, but well‐controlled studies in humans without confounding conditions are lacking. Thus, the ...purpose of the present study was to investigate whether ACE inhibition affects cardiovascular adaptations to exercise training in healthy humans. Healthy participants of both genders (40 ± 7 years) completed a randomized, double‐blind, placebo‐controlled trial. Eight weeks of exercise training combined with placebo (PLA, n = 25) or ACE inhibitor (ACEi, n = 23) treatment was carried out. Before and after the intervention, cardiovascular characteristics were investigated. Mean arterial blood pressure was reduced (p < 0.001) by −5.5 −8.4; −2.6 mmHg in ACEi, whereas the 0.7 −2.0; 3.5 mmHg fluctuation in PLA was non‐significant. Maximal oxygen uptake increased (p < 0.001) irrespective of ACE inhibitor treatment by 13 8; 17 % in ACEi and 13 9; 17 % in PLA. In addition, skeletal muscle endurance increased (p < 0.001) to a similar extent in both groups, with magnitudes of 82 55; 113 % in ACEi and 74 48; 105 % in PLA. In contrast, left atrial volume decreased (p < 0.05) by −9 −16; −2 % in ACEi, but increased (p < 0.01) by 14 5; 23 % in PLA. Total hemoglobin mass was reduced (p < 0.01) by −3 −6; −1 % in ACEi, while a non‐significant numeric increase of 2 −0.4; 4 % existed in PLA. The lean mass remained constant in ACEi but increased (p < 0.001) by 3 2; 4 % in PLA. In healthy middle‐aged adults, 8 weeks of high‐intensity exercise training increases maximal oxygen uptake and skeletal muscle endurance irrespective of ACE inhibitor treatment. However, ACE inhibitor treatment counteracts exercise training‐induced increases in lean mass and left atrial volume. ACE inhibitor treatment compromises total hemoglobin mass.
A high‐intensity endurance exercise training program improves maximal oxygen uptake, whole‐body work capacity, and muscle endurance, with no effect of ACE inhibitor treatment, in normotensive adults. However, ACE inhibitor treatment impairs the exercise‐induced increase in lean mass and left atrial volume and compromises total hemoglobin mass. Results are presented as means with 95% confidence intervals. *p < 0.05, **p < 0.001 for the within‐group change (∆) from baseline from a paired samples t‐test, and #p < 0.05 for the between‐group difference in change from baseline from an independent samples t‐test in participants treated with an angiotensin‐converting enzyme inhibitor (ACEi) or placebo. CMR, cardiovascular magnetic resonance imaging.
The novel hypothesis that "Live High-Train Low" (LHTL) does not improve sport-specific exercise performance (e.g., time trial) is discussed. Indeed, many studies demonstrate improved performance ...after LHTL but, unfortunately, control groups are often lacking, leaving open the possibility of training camp effects. Importantly, when control groups, blinding procedures, and strict scientific evaluation criteria are applied, LHTL has no detectable effect on performance.