15 weeks of soccer training increases left ventricular mass and improves indices of left ventricular diastolic function in previously sedentary, mildly hypertensive, middle-aged women.

PURPOSE: To investigate the impact of soccer training on cardiac adaptations in mildly hypertensive middle-aged women. METHODS: Hypertensive premenopausal women (n = 41; age (mean ± SD): 44 ± 7 years; height: 166 ± 6 cm; weight: 78.6 ± 11.6 kg; body fat: 43.3 ± 5.2%) were randomized to soccer training (SOC, n = 21) or control (CON, n = 20). SOC performed three weekly training sessions for 15 weeks, whereas CON had no training or lifestyle changes during the same period. Cardiac structure and function were assessed by echocardiography pre-intervention and post-intervention. RESULTS: Soccer training increased (P = 0.001) left ventricular mass index by 10% [95% CI 4; 15], while no changes occurred in CON (time × group interaction, P = 0.005). In addition, only SOC demonstrated a within-group increase (P = 0.01) of 8% [95% CI 2; 14] in left ventricular septum diameter. For markers of right ventricular remodelling, a within-group increase (P = 0.02) occurred for tricuspid annulus plane systolic excursion of 8% [95% CI 1; 14] in SOC only. Left atrial diameter index increased (P < 0.001) by 6% [95% CI 3; 10] after SOC, while it was unaffected in CON (time × group interaction, P = 0.02). For makers of diastolic function, SOC demonstrated a within-group increase (P = 0.02) in the average early diastolic mitral annulus velocity of 10% [95% CI 2; 19]. In addition, a reduction (P < 0.001) in mitral valve A velocity of - 19% [95% CI - 29; - 10] was observed following soccer training, which manifested in increased (P < 0.001) mitral valve E/A ratio of 34% [95% CI 16; 53] in SOC. No within-group changes were apparent in CON. CONCLUSION: In sedentary, mildly hypertensive, middle-aged women, 15 weeks of soccer training increases left ventricular mass and left atrial diameter and improves indices of left ventricular diastolic function.

Robust arm and leg muscle adaptation to training despite ACE inhibition: a randomized placebo-controlled trial.

PURPOSE: Angiotensin-converting enzyme (ACE) inhibitor treatment is widely applied, but the fact that plasma ACE activity is a potential determinant of training-induced local muscular adaptability is often neglected. Thus, we investigated the hypothesis that ACE inhibition modulates the response to systematic aerobic exercise training on leg and arm muscular adaptations. METHODS: Healthy, untrained, middle-aged participants (40 ± 7 yrs) completed a randomized, double-blinded, placebo-controlled trial. Participants were randomized to placebo (PLA: CaCO3) or ACE inhibitor (ACEi: enalapril) for 8 weeks and completed a supervised, high-intensity exercise training program. Muscular characteristics in the leg and arm were extensively evaluated pre and post-intervention. RESULTS: Forty-eight participants (nACEi = 23, nPLA = 25) completed the trial. Exercise training compliance was above 99%. After training, citrate synthase, 3-hydroxyacyl-CoA dehydrogenase and phosphofructokinase maximal activity were increased in m. vastus lateralis in both groups (all P < 0.05) without statistical differences between them (all time × treatment P > 0.05). In m. deltoideus, citrate synthase maximal activity was upregulated to a greater extent (time × treatment P < 0.05) in PLA (51 [33;69] %) than in ACEi (28 [13;43] %), but the change in 3-hydroxyacyl-CoA dehydrogenase and phosphofructokinase maximal activity was similar between groups. Finally, the training-induced changes in the platelet endothelial cell adhesion molecule-1 protein abundance, a marker of capillary density, were similar in both groups in m. vastus lateralis and m. deltoideus. CONCLUSION: Eight weeks of high-intensity whole-body exercise training improves markers of skeletal muscle mitochondrial oxidative capacity, glycolytic capacity and angiogenesis, with no overall effect of pharmacological ACE inhibition in healthy adults.

Directly measured aerobic fitness in male Maasai of Tanzania.

OBJECTIVES: The agro-pastoralist Maasai of East Africa are highly physically active, but their aerobic fitness has so far only been estimated using heart rate (HR) response to submaximal exercise and not directly measured. Thus, we aimed to measure aerobic fitness directly using respiratory gas analysis in a group of Maasai, and habitual physical activity energy expenditure (PAEE) as explanatory variable. METHODS: In total, 21 (10 rural, 11 semi-urban) of 30 volunteering Tanzanian Maasai men were eligible to participate. Respiratory gas exchange was measured during a graded exercise test until exhaustion on a stationary bicycle to determine aerobic fitness. Maximal effort criteria were at least two of the following (1) leveling off, (2) respiratory exchange ratio (RER) >1.10, and (3) maximum HR within 10 bpm of age-estimated maximum HR. Habitual PAEE was estimated using combined accelerometry and HR monitoring. Anthropometry, biochemistry, blood pressure, resting HR, and dietary intake information were collected for background information. RESULTS: Mean age was 43.2 (range 26-60) years, and hemoglobin was higher in the rural versus semi-urban Maasai (16.9 vs. 15.4 g/dl, p = .02). Mean aerobic fitness (34.4 vs. 33.3 mlO2 /min/kg, p = .79), and mean PAEE (58.5 vs. 52.9 kJ/day/kg, p = .64) were similar in rural and semi-urban Maasai, respectively. CONCLUSIONS: Aerobic fitness was low to moderate in male rural and semi-urban Maasai. This may be explained by relatively low PAEE in comparison to previous objectively measured activity levels in Maasai, which indicates recent lifestyle changes.

Human muscular mitochondrial fusion in athletes during exercise.

The main objective of this work was to investigate whether mitochondrial fusion occurs in the skeletal muscle of well-trained athletes in response to high-intensity exercise. Well-trained swimmers (n = 9) performed a duration-matched sprint interval training (SIT) and high-intensity high-volume training (HIHVT) session on separate days. Muscle samples from triceps brachii were taken before, immediately after, and 3 h after the training sessions. Transmission electron microscopy (TEM) was applied to assess mitochondrial morphology. Moreover, expression of genes coding for regulators of mitochondrial fusion and fission were assessed by real-time quantitative PCR. In addition, mitofusin (MFN)2 and optic atrophy 1 (OPA1) were quantified by Western blot analysis. TEM analyses showed that mitochondrial morphology remained altered for 3 h after HIHVT, whereas SIT-induced changes were only evident immediately after exercise. Only SIT increased MFN1 and MFN2 mRNA expression, whereas SIT and HIHVT both increased MFN2 protein content 3 h after exercise. Notably, only HIHVT increased OPA1 protein content. Mitochondrial morphologic changes that suggest fusion occurs in well-adapted athletes during exercise. However, HIHVT appears as a more robust inducer of mitochondrial fusion events than SIT. Indeed, SIT induces a rapid and transient change in mitochondrial morphology.-Huertas, J. R., Ruiz-Ojeda, F. J., Plaza-Díaz, J., Nordsborg, N. B., Martín-Albo, J., Rueda-Robles, A., Casuso, R. A. Human muscular mitochondrial fusion in athletes during exercise.

The impact of exercise training complementary to early intervention in patients with first-episode psychosis: a qualitative sub-study from a randomized controlled feasibility trial.

BACKGROUND: Burgeoning evidence suggests that exercise improves physical and mental health in people with schizophrenia. However, little is known about the feasibility and acceptability of high-intensity training in patients with first-episode psychosis. This qualitative study explored motivation, social interaction and experiences of participants and instructors in relation to an eight-week moderate to high intensity exercise training programme in a clinical trial including patients with first-episode psychosis. METHODS: The study used a combination of method, source and investigator triangulation. Data were collected by means of semi-structured individual interviews with participants at baseline (n = 16) and at follow-up (n = 9), as well as by means of participant observations during the programme (8 sessions × 1.5 h, 12 h in total) and focus group discussions with participants (n = 3) and instructors (n = 4), respectively, after the programme. Data were analysed using thematic analysis as described by Braun and Clarke. RESULTS: Three main themes and ten subthemes emerged during the analysis: 1) motivation and expectations for enrolment (subthemes: routines and structure, social obligation, goal setting and self-worth); 2) new demands and opportunities (subthemes: practicalities of the training, an understanding exercise setting, and alone and together); and 3) looking ahead - reflections on impact (subthemes: restored sleep and circadian rhythm, energy and sense of achievement, changed everyday life, and hope of finding a new path). Findings suggest that the programme was appealing to, and appreciated by, the participants because of its potential to create an equally challenging and caring non-clinical environment. CONCLUSIONS: This study indicates that supervised, group-based, moderate to high intensity exercise training complementary to early intervention in psychosis is acceptable. Specifically, the intervention appeared to provide patients an opportunity to integrate the notion of being a young individual along with being a patient with a psychiatric diagnosis, thus supporting and promoting recovery. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT03409393. Registered January 24, 2018.

Low-volume high-intensity swim training is superior to high-volume low-intensity training in relation to insulin sensitivity and glucose control in inactive middle-aged women.

PURPOSE: We tested the hypothesis that low-volume high-intensity swimming has a larger impact on insulin sensitivity and glucose control than high-volume low-intensity swimming in inactive premenopausal women with mild hypertension. METHODS: Sixty-two untrained premenopausal women were randomised to an inactive control (n = 20; CON), a high-intensity low-volume (n = 21; HIT) or a low-intensity high-volume (n = 21; LIT) training group. During the 15-week intervention period, HIT performed 3 weekly 6-10 × 30-s all-out swimming intervals (average heart rate (HR) = 86 ± 3 % HRmax) interspersed by 2-min recovery periods and LIT swam continuously for 1 h at low intensity (average HR = 73 ± 3 % HRmax). Fasting blood samples were taken and an oral glucose tolerance test (OGTT) was conducted pre- and post-intervention. RESULTS: After HIT, resting plasma [insulin] was lowered (17 ± 34 %; P < 0.05) but remained similar after LIT and CON. Following HIT, 60-min OGTT plasma [insulin] and [glucose] was lowered (24 ± 30 % and 10 ± 16 %; P < 0.05) but remained similar after LIT and CON. Total area under the curve for plasma [glucose] was lower (P < 0.05) after HIT than LIT (660 ± 141 vs. 860 ± 325 mmol min L(-1)). Insulin sensitivity (HOMA-IR) had increased (P < 0.05) by 22 ± 34 % after HIT, with no significant change after LIT or CON, respectively. Plasma soluble intracellular cell adhesion molecule 1 was lowered (P < 0.05) by 4 ± 8 and 3 ± 9 % after HIT and CON, respectively, while plasma soluble vascular cell adhesion molecule 1 had decreased (P < 0.05) by 8 ± 23 % after HIT only. CONCLUSIONS: These findings suggest that low-volume high-intensity intermittent swimming is an effective and time-efficient training strategy for improving insulin sensitivity, glucose control and biomarkers of vascular function in inactive, middle-aged mildly hypertensive women.

Adaptations to Short, Frequent Sessions of Endurance and Strength Training Are Similar to Longer, Less Frequent Exercise Sessions When the Total Volume Is the Same.

The hypothesis that the distribution of weekly training across several short sessions, as opposed to fewer longer sessions, enhances maximal strength gain without compromising maximal oxygen uptake was evaluated. Twenty-nine subjects completed an 8-week controlled parallel-group training intervention. One group ("micro training" [MI]: n = 21) performed nine 15-minute training sessions weekly, whereas a second group ("classical training" [CL]: n = 8) completed exactly the same training on a weekly basis but as three 45-minute sessions. For each group, each session comprised exclusively strength, high-intensity cardiovascular training or muscle endurance training. Both groups increased shuttle run performance (MI: 1,373 ± 133 m vs. 1,498 ± 126 m, p ≤ 0.05; CL: 1,074 ± 213 m vs. 1,451 ± 202 m, p < 0.001). In contrast to CL, MI increased peak oxygen uptake (3,744 ± 615 mL·min⁻¹ vs. 3,963 ± 753 mL·min⁻¹, p ≤ 0.05), maximal voluntary isometric (MVC) force of the knee extensors (646 ± 135 N vs. 659 ± 209 N, p < 0.001), MVC of the finger flexors (408 ± 109 N vs. 441 ± 131 N, p ≤ 0.05), and number of lunges performed in 2 minutes (65 ± 3 vs. 73 ± 2, p < 0.001). However, there were no significant differences between MI and CL on any measured parameters before or after the training intervention. In conclusion, similar training adaptations can be obtained with short, frequent exercise sessions or longer, less frequent sessions where the total volume of weekly training performed is the same.

Phlebotomy eliminates the maximal cardiac output response to six weeks of exercise training.

With this study we tested the hypothesis that 6 wk of endurance training increases maximal cardiac output (Qmax) relatively more by elevating blood volume (BV) than by inducing structural and functional changes within the heart. Nine healthy but untrained volunteers (Vo2max 47 ± 5 ml·min(-1)·kg(-1)) underwent supervised training (60 min; 4 times weekly at 65% Vo2max for 6 wk), and Qmax was determined by inert gas rebreathing during cycle ergometer exercise before and after the training period. After the training period, blood volume (determined in duplicates by CO rebreathing) was reestablished to pretraining values by phlebotomy and Qmax was quantified again. Resting echography revealed no structural heart adaptations as a consequence of the training intervention. After the training period, plasma volume (PV), red blood cell volume (RBCV), and BV increased (P < 0.05) by 147 ± 168 (5 ± 5%), 235 ± 64 (10 ± 3%), and 382 ± 204 ml (7 ± 4%), respectively. Vo2max was augmented (P < 0.05) by 10 ± 7% after the training period and decreased (P < 0.05) by 8 ± 7% with phlebotomy. Concomitantly, Qmax was increased (P < 0.05) from 18.9 ± 2.1 to 20.4 ± 2.3 l/min (9 ± 6%) as a consequence of the training intervention, and after normalization of BV by phlebotomy Qmax returned to pretraining values (18.1 ± 2.5 l/min; 12 ± 5% reversal). Thus the exercise training-induced increase in BV is the main mechanism increasing Qmax after 6 wk of endurance training in previously untrained subjects.

Lactate oxidation in human skeletal muscle mitochondria.

Lactate is an important intermediate metabolite in human bioenergetics and is oxidized in many different tissues including the heart, brain, kidney, adipose tissue, liver, and skeletal muscle. The mechanism(s) explaining the metabolism of lactate in these tissues, however, remains unclear. Here, we analyze the ability of skeletal muscle to respire lactate by using an in situ mitochondrial preparation that leaves the native tubular reticulum and subcellular interactions of the organelle unaltered. Skeletal muscle biopsies were obtained from vastus lateralis muscle in 16 human subjects. Samples were chemically permeabilized with saponin, which selectively perforates the sarcolemma and facilitates the loss of cytosolic content without altering mitochondrial membranes, structure, and subcellular interactions. High-resolution respirometry was performed on permeabilized muscle biopsy preparations. By use of four separate and specific substrate titration protocols, the respirometric analysis revealed that mitochondria were capable of oxidizing lactate in the absence of exogenous LDH. The titration of lactate and NAD(+) into the respiration medium stimulated respiration (P ≤ 0.003). The addition of exogenous LDH failed to increase lactate-stimulated respiration (P = 1.0). The results further demonstrate that human skeletal muscle mitochondria cannot directly oxidize lactate within the mitochondrial matrix. Alternately, these data support previous claims that lactate is converted to pyruvate within the mitochondrial intermembrane space with the pyruvate subsequently taken into the mitochondrial matrix where it enters the TCA cycle and is ultimately oxidized.

Exercise-induced increase in maximal in vitro Na-K-ATPase activity in human skeletal muscle.

The present study investigated whether maximal in vitro Na-K-ATPase activity in human skeletal muscle is changed with exercise and whether it was altered by acute hypoxia. Needle biopsies from 14 subjects were obtained from vastus lateralis before and after 4 min of intense muscle activity. In addition, six subjects exercised also in hypoxia (12.5% oxygen). The Na-K-ATPase assay revealed a 19% increase (P < 0.05) in maximal velocity (Vmax) for Na⁺-dependent Na-K-ATPase activity after exercise and a tendency (P < 0.1) toward a decrease in Km for Na⁺ (increased Na⁺ affinity) in both normoxia and hypoxia. In contrast, the in vitro Na-K-ATPase activity determined with the 3-O-MFPase technique was 11-32% lower after exercise in normoxia (P < 0.05) and hypoxia (P < 0.1). Based on the different results obtained with the Na-K-ATPase assay and the 3-O-MFPase technique, it was suggested that the 3-O-MFPase method is insensitive to changes in Na-K-ATPase activity. To test this possibility, changes in Na-K-ATPase activity was induced by protein kinase C activation. The changes quantified with the Na-K-ATPase assay could not be detected with the 3-O-MFPase method. In addition, purines stimulated Na-K-ATPase activity in rat muscle membranes; these changes could not be detected with the 3-O-MFPase method. Therefore, the 3-O-MFPase technique is not sensitive to changes in Na⁺ sensitivity, and the method is not suited to detecting changes in Na-K-ATPase activity with exercise. In conclusion, muscle activity in humans induces an increased in vitro Na⁺-dependent Na-K-ATPase activity, which contributes to the upregulation of the Na-K-ATPase in association with exercise both in normoxia and hypoxia.

Long-term continuous exercise training counteracts the negative impact of the menopause transition on cardiometabolic health in hypertensive women - a 9-year RCT follow-up.

PURPOSE: The study examined effects of 9-yrs of multicomponent exercise training during the menopause interval on cardiometabolic health in hypertensive women. METHODS: Sedentary, middle-aged women (n = 25) with mild-to-moderate arterial hypertension were randomized into a soccer training (multicomponent exercise; EX; n = 12) or control group (CON; n = 13). EX took part in 1-h football training sessions, 1-3 times weekly, for a consecutive 9-years, totaling ∼800 training sessions, while CON did not take part in regular exercise training. 22 participants entered menopause during the intervention. RESULTS: A time×group interaction effect (P = 0.04) of 8.5 mmHg in favour of EX was observed for changes in mean arterial pressure (MAP) (EX: -4.8 [-10.7;1.1] mmHg, CON +3.7 [-2.0;9.3] mmHg). Time×group interaction effects in favour of EX were also observed for total body weight (4.6 kg, P = 0.008, EX: +0.7 [-1.7;3.0] kg, CON: +5.3 [3.0;7.6] kg, total fat percentage (5.7%-points, P = 0.02; EX (-1.9 [-4.4;0.6] %-points; P = 0.13), CON +3.8 [1.4;6.2] %-points and for total cholesterol (1.2 mmol/l, P = 0.03, EX: -0.5 [-1.0;-0.1] mmol/l, CON: +0.7 [0.2;1.1] mmol/l. EX reduced (P = 0.02) plasma low-density lipoprotein cholesterol by -0.4 [-0.8;-0.1] mmol/l, whereas an increase (P = 0.01) of 0.4 [0.1;0.8] mmol/l occurred in CON (interaction. P < 0.001). A time×group interaction (P = 0.004) existed for changes in exercise capacity in favour of EX. Fasting glucose remained unchanged in EX and increased (P < 0.001) by 0.7 [0.4;1.0] mmol/l in CON (time×group interaction P = 0.02). CONCLUSION: In conclusion, long-term multicomponent exercise training fully counteracts the detrimental effects of the menopause transition on cardiometabolic health in hypertensive women.

Microdoses of Recombinant Human Erythropoietin Enhance Time Trial Performance in Trained Males and Females.

PURPOSE: We investigated the effects of recombinant human erythropoietin (rHuEPO) administration on exercise endurance, maximal aerobic performance, and total hemoglobin mass (tHb). We hypothesized that frequent, small intravenous injections of epoetin ß would increase time trial performance, peak oxygen uptake (V̇O 2peak ), and tHb in both males and females. METHODS: We included 48 healthy, recreational to trained males ( n = 24, mean ± SD V̇O 2peak = 55 ± 5 mL O 2 ·kg -1 ⋅min -1 ) and females ( n = 24; V̇O 2peak of 46 ± 4 mL O 2 ·kg -1 ⋅min -1 ) in a counterbalanced, double-blind, randomized, placebo-controlled study design stratified by sex. Time trial performance, V̇O 2peak , and tHb were determined before and after intravenous injections of either rHuEPO (9 IU·kg bw -1 epoetin ß) or saline (0.9% NaCl) three times weekly for 4 wk. RESULTS: A time-treatment effect ( P < 0.05) existed for time trial performance. Within the rHuEPO group, mean power output increased by 4.1% ± 4.2% ( P < 0.001). Likewise, a time-treatment effect ( P < 0.001) existed for V̇O 2peak , where the rHuEPO group improved V̇O 2peak and peak aerobic power by 4.2% ± 6.1% ( P < 0.001) and 2.9% ± 4.0% ( P < 0.01), respectively. A time-treatment effect ( P < 0.001) existed for tHb, where the rHuEPO group increased tHb by 6.7% ± 3.4% ( P < 0.001). A main effect of "sex" alone was also evident ( P < 0.001), but no sex-specific interactions were found. No changes were observed in the placebo group for mean power output, V̇O 2peak , peak aerobic power, or tHb. CONCLUSIONS: Microdoses with intravenous rHuEPO provide a sufficient erythropoietic stimuli to augment tHb and enhance aerobic-dominated performance in both trained males and females.

The angiotensin-converting enzyme I/D polymorphism does not impact training-induced adaptations in exercise capacity in patients with stable coronary artery disease.

Systematic exercise training effectively improves exercise capacity in patients with coronary artery disease (CAD), but the magnitude of improvements is highly heterogeneous. We investigated whether this heterogeneity in exercise capacity gains is influenced by the insertion/deletion (I/D) polymorphism of the angiotensin-converting enzyme (ACE) gene. Patients with CAD (n = 169) were randomly assigned to 12 weeks of exercise training or standard care, and 142 patients completed the study. The ACE polymorphism was determined for 128 patients (82% males, 67 ± 9 years). Peak oxygen uptake was measured before and after the 12-week intervention. The ACE I/D polymorphism frequency was n = 48 for D/D homozygotes, n = 61 for I/D heterozygotes and n = 19 for I/I homozygotes. Baseline peak oxygen uptake was 23.3 ± 5.0 ml/kg/min in D/D homozygotes, 22.1 ± 5.3 ml/kg/min in I/D heterozygotes and 23.1 ± 6.0 ml/kg/min in I/I homozygotes, with no statistical differences between genotype groups (P = 0.50). The ACE I/D polymorphism frequency in the exercise group was n = 26 for D/D, n = 21 for I/D and n = 12 for I/I. After exercise training, peak oxygen uptake was increased (P < 0.001) in D/D homozygotes by 2.6 ± 1.7 ml/kg/min, in I/D heterozygotes by 2.7 ± 1.9 ml/kg/min, and in I/I homozygotes by 2.1 ± 1.3 ml/kg/min. However, the improvements were similar between genotype groups (time × genotype, P = 0.55). In conclusion, the ACE I/D polymorphism does not affect baseline exercise capacity or exercise capacity gains in response to 12 weeks of high-intensity exercise training in patients with stable CAD.Clinical trial registration: www.clinicaltrials.gov (NCT04268992).

Serum Insulin-like Factor 3, Testosterone, and LH in Experimental and Therapeutic Testicular Suppression.

BACKGROUND: Serum insulin-like factor 3 (INSL3) is a Leydig cell biomarker, but little is known about the circulating concentration of INSL3 during hypothalamus-pituitary-testicular suppression. AIM: To study the concomitant changes in serum concentrations of INSL3, testosterone, and LH during experimental and therapeutic testicular suppression. METHODS: We included serum samples from 3 different cohorts comprising subjects before and after testicular suppression: (1) 6 healthy young men who were treated with androgens (Sustanon, Aspen Pharma, Dublin, Ireland); 2) 10 transgender girls (male sex assigned at birth) who were treated with 3-monthly GnRH agonist injections (Leuprorelinacetat, Abacus Medicine, Copenhagen, Denmark); and (3) 55 patients with prostate cancer who were randomized to surgical castration (bilateral subcapsular orchiectomy) or treatment with GnRH agonist (Triptorelin, Ipsen Pharma, Kista, Sweden). Serum INSL3 and testosterone concentrations were quantified in stored serum samples using validated liquid chromatography-tandem mass spectrometry methodologies, and LH was measured by an ultrasensitive immunoassay. RESULTS: The circulating concentrations of INSL3, testosterone, and LH decreased during experimental testicular suppression in healthy young men by Sustanon injections and subsequently returned to baseline levels after release of suppression. All 3 hormones decreased during therapeutic hormonal hypothalamus-pituitary-testicular suppression in transgender girls and in patients with prostate cancer. CONCLUSION: INSL3 resembles testosterone as a sensitive marker of testicular suppression and reflects Leydig cell function, also during exposure to exogenous testosterone. Serum INSL3 measurements may complement testosterone as a Leydig cell marker in male reproductive disorders, during therapeutic testicular suppression as well as in surveillance of illicit use of androgens.

Oxygen Uptake During Activities of Daily Life in Patients Treated With a Left Ventricular Assist Device.

INTRODUCTION: Oxygen consumption during activities of daily life (ADL) is not described in recipients of left ventricular assist device (LVAD). We aimed to investigate the relation between oxygen consumption during predefined ADLs and measures of functional capacity (FC) in stable-phase LVAD recipients. METHODS: LVADs and controls were matched on gender, age, BMI, smoking status, and ethnicity. VO2 was measured using mobile equipment (K5, Cosmed, Rome, Italy) while putting on vest and LVAD equipment(1), folding towels(2), putting on socks and shoes(3), putting bottles in a cupboard(4), making a bed(5), walking on stairs without(6) and with extra weight(7), and sweeping the floor(8). Submaximal FC was tested by means of 6 minute walk test (6MWT) and peak oxygen uptake (pVO2) to test maximal FC. RESULTS: Fifteen LVAD patients and 16 controls were included; Patients were 61 ± 10years, all males with BMI 28 ± 5kg/m2 and implanted with Heartmate 3 (DT: 60%). PVO2 was 14.9 ± 2.2 ml/kg/min in patients and 39.6 ± 7.7 in controls (p < 0.001). Oxygen consumption expressed as percent of pVO2 for each task in patients vs controls was (%): ADL1: 41 ± 5 vs 21 ± 4, ADL2: 41 ± 6 vs 22 ± 5 %, ADL3: 50 ± 16 vs 24 ± 5%, ADL4: 45 ± 12 vs 22 ± 4, ADL5: 50 ± 8 vs 23 ± 4, ADL6: 66 ± 10 vs 30 ± 4, ADL7: 65 ± 10 vs 31 ± 5, ADL8: 75 ± 10 vs 39 ± 12, (p < 0.001 for all). During 6MWT LVAD patients used 96% ± 8 % of their pVO2. CONCLUSION: Recipients of durable LVADs perform daily life activities at oxygen uptake levels much closer to their peak cardiopulmonary reserve than matched healthy controls.

Analysis of dried blood spots is a feasible alternative for detecting ephedrine in doping control.

Dried blood spot (DBS) testing allows fast, easy and minimally invasive collection of microvolumes of blood. In an anti-doping context, DBS testing has particular relevance for substances prohibited in-competition only such as ephedrine, which is currently detected by urine analysis, because DBS can add information about the blood drug concentrations during the in-competition period. Several collection methods and devices exist for DBS collection from different anatomical sites. Thus, agreements between concentrations of target analytes in DBS samples from different sampling sites, along with between DBS and those in conventional venous plasma samples, need to be evaluated. Herein, we collected matched upper-arm DBS, fingerprick DBS and venous plasma samples from eight healthy male subjects in an 8-h period following oral administrations of 20 mg ('low dose') and 60 mg ('high dose') of ephedrine. We show that the use of alternative sampling sites and matrices is a feasible possibility for ephedrine analysis in doping control. We observed very good agreement between collection sites and that specificity and sensitivity can be upheld despite use of an alternative collection site. However, potential concentration differences between DBS and venous plasma should be considered, and distinct threshold might be necessary if implementing both blood matrices in ephedrine analysis.

Does Hypoxia and Stress Erythropoiesis Compromise Cardiac Function in Healthy Adults? A Randomized Trial.

OBJECTIVES: To investigate whether recombinant human erythropoietin (rHuEPO) injections during an altitude training camp impact heart function. METHODS: Thirty (12 women) moderately trained subjects stayed at 2320 m altitude for 4 weeks while training. Subjects were randomized to placebo (isotonic saline) or rHuEPO (20 IU/kg body weight) i.v. injections. Transthoracic echocardiography imaging was acquired 3 days after arrival to altitude and prior to the first placebo or rHuEPO injection as well as one day after the last rHuEPO injection three weeks later. RESULTS: rHuEPO did not alter cardiovascular morphology parameters, systolic or diastolic function. In the placebo group, altitude exposure improved left ventricle (LV) systolic function due to an increased twist angle but rHuEPO had no additional effects. Pulmonary arterial systolic pressure was unaffected in either group. Notably, rHuEPO hampered LV untwist rate without affecting LV early filling. CONCLUSION: rHuEPO provided during mild altitude exposure does not cause any major effects on heart function. The observed alteration in LV untwist induced by rHuEPO is unlikely to have a meaningful clinical effect. Trial Registration Registered on www. CLINICALTRIALS: gov (NCT04227665).

Effect of angiotensin-converting enzyme inhibition on cardiovascular adaptation to exercise training.

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.

Exercise-induced regulation of muscular Na+-K+ pump, FXYD1, and NHE1 mRNA and protein expression: importance of training status, intensity, and muscle type.

It is investigated if exercise-induced mRNA changes cause similar protein expression changes of Na(+)-K(+) pump isoforms (α(1), α(2), ß(1), ß(2)), FXYD1, and Na(+)/K(+) exchanger (NHE1) in rat skeletal muscle. Expression was evaluated (n = 8 per group) in soleus and extensor digutorum longus after 1 day, 3 days, and 3 wk (5 sessions/wk) of either sprint (4 × 3-min sprint + 1-min rest) or endurance (20 min) running. Two hours after exercise on day 1, no change in protein expression was apparent in either training group or muscle, whereas sprint exercise increased the mRNA of soleus α(2) (4.9 ± 0.8-fold; P < 0.05), ß(2) (13.2 ± 4.4-fold; P < 0.001), and NHE1 (12.0 ± 3.1-fold; P < 0.01). Two hours after sprint exercise, protein expression normalized to control samples was higher on day 3 than day 1 for soleus α(1) (41 ± 18% increase vs. 15 ± 8% reduction; P < 0.05), α(2) (64 ± 35% increase vs. 37 ± 12% reduction; P < 0.05), ß(1) (17 ± 21% increase vs. 14 ± 29% reduction; P < 0.05), and FXYD1 (35 ± 16% increase vs. 13 ± 10% reduction; P < 0.05). In contrast, on day 3, soleus α(1) (0.1 ± 0.1-fold; P < 0.001), α(2) (0.2 ± 0.1-fold; P < 0.001), ß(1) (0.4 ± 0.1-fold; P < 0.05), and ß(2)-mRNA (2.9 ± 1.7-fold; P < 0.001) expression was lower than after exercise on day 1. After 3 wk of training, no change in protein expression relative to control existed. In conclusion, increased expression of Na(+)-K(+) pump subunits, FXYD1 and NHE1 after 3 days exercise training does not appear to be an effect of increased constitutive mRNA levels. Importantly, sprint exercise can reduce mRNA expression concomitant with increased protein expression.

Protein kinase Cα activity is important for contraction-induced FXYD1 phosphorylation in skeletal muscle.

Exercise-induced phosphorylation of FXYD1 is a potential important regulator of Na(+)-K(+)-pump activity. It was investigated whether skeletal muscle contractions induce phosphorylation of FXYD1 and whether protein kinase Cα (PKCα) activity is a prerequisite for this possible mechanism. In part 1, human muscle biopsies were obtained at rest, after 30 s of high-intensity exercise (166 ± 31% of Vo(2max)) and after a subsequent 20 min of moderate-intensity exercise (79 ± 8% of Vo(2max)). In general, FXYD1 phosphorylation was increased compared with rest both after 30 s (P < 0.05) and 20 min (P < 0.001), and more so after 20 min compared with 30 s (P < 0.05). Specifically, FXYD1 ser63, ser68, and combined ser68 and thr69 phosphorylation were 26-45% higher (P < 0.05) after 20 min of exercise than at rest. In part 2, FXYD1 phosphorylation was investigated in electrically stimulated soleus and EDL muscles from PKCα knockout (KO) and wild-type (WT) mice. Contractile activity caused FXYD1 ser68 phosphorylation to be increased (P < 0.001) in WT soleus muscles but to be reduced (P < 0.001) in WT extensor digitorum longus. In contrast, contractile activity did not affect FXYD1 ser68 phosphorylation in the KO mice. In conclusion, exercise induces FXYD1 phosphorylation at multiple sites in human skeletal muscle. In mouse muscles, contraction-induced changes in FXYD1 ser68 phosphorylation are fiber-type specific and dependent on PKCα activity.