An endothelial regulatory module links blood pressure regulation with elite athletic performance.

The control of transcription is crucial for homeostasis in mammals. A previous selective sweep analysis of horse racing performance revealed a 19.6 kb candidate regulatory region 50 kb downstream of the Endothelin3 (EDN3) gene. Here, the region was narrowed to a 5.5 kb span of 14 SNVs, with elite and sub-elite haplotypes analyzed for association to racing performance, blood pressure and plasma levels of EDN3 in Coldblooded trotters and Standardbreds. Comparative analysis of human HiCap data identified the span as an enhancer cluster active in endothelial cells, interacting with genes relevant to blood pressure regulation. Coldblooded trotters with the sub-elite haplotype had significantly higher blood pressure compared to horses with the elite performing haplotype during exercise. Alleles within the elite haplotype were part of the standing variation in pre-domestication horses, and have risen in frequency during the era of breed development and selection. These results advance our understanding of the molecular genetics of athletic performance and vascular traits in both horses and humans.

Sports genetics moving forward: lessons learned from medical research.

Sports genetics can take advantage of lessons learned from human disease genetics. By righting past mistakes and increasing scientific rigor, we can magnify the breadth and depth of knowledge in the field. We present an outline of challenges facing sports genetics in the light of experiences from medical research. Sports performance is complex, resulting from a combination of a wide variety of different traits and attributes. Improving sports genetics will foremost require analyses based on detailed phenotyping. To find widely valid, reproducible common variants associated with athletic phenotypes, study sample sizes must be dramatically increased. One paradox is that in order to confirm relevance, replications in specific populations must be undertaken. Family studies of athletes may facilitate the discovery of rare variants with large effects on athletic phenotypes. The complexity of the human genome, combined with the complexity of athletic phenotypes, will require additional metadata and biological validation to identify a comprehensive set of genes involved. Analysis of personal genetic and multiomic profiles contribute to our conceptualization of precision medicine; the same will be the case in precision sports science. In the refinement of sports genetics it is essential to evaluate similarities and differences between sexes and among ethnicities. Sports genetics to date have been hampered by small sample sizes and biased methodology, which can lead to erroneous associations and overestimation of effect sizes. Consequently, currently available genetic tests based on these inherently limited data cannot predict athletic performance with any accuracy.

Mitochondria-targeted dodecyltriphenylphosphonium (C12TPP) combats high-fat-diet-induced obesity in mice.

BACKGROUND: A membrane-penetrating cation, dodecyltriphenylphosphonium (C12TPP), facilitates the recycling of fatty acids in the artificial lipid membrane and mitochondria. C12TPP can dissipate mitochondrial membrane potential and may affect total energy expenditure and body weight in animals and humans. METHODS: We investigated the metabolic effects of C12TPP in isolated brown-fat mitochondria, brown adipocyte cultures and mice in vivo. Experimental approaches included the measurement of oxygen consumption, carbon dioxide production, western blotting, magnetic resonance imaging and bomb calorimetry. RESULTS: In mice, C12TPP (50 µmol per (day•kg body weight)) in the drinking water significantly reduced body weight (12%, P<0.001) and body fat mass (24%, P<0.001) during the first 7 days of treatment. C12TPP did not affect water palatability and intake or the energy and lipid content in feces. The addition of C12TPP to isolated brown-fat mitochondria resulted in increased oxygen consumption. Three hours of pretreatment with C12TPP also increased oligomycin-insensitive oxygen consumption in brown adipocyte cultures (P<0.01). The effects of C12TPP on mitochondria, cells and mice were independent of uncoupling protein 1 (UCP1). However, C12TPP treatment increased the mitochondrial protein levels in the brown adipose tissue of both wild-type and UCP1-knockout mice. Pair-feeding revealed that one-third of the body weight loss in C12TPP-treated mice was due to reduced food intake. C12TPP treatment elevated the resting metabolic rate (RMR) by up to 18% (P<0.05) compared with pair-fed animals. C12TPP reduced the respiratory exchange ratio, indicating enhanced fatty acid oxidation in mice. CONCLUSIONS: C12TPP combats diet-induced obesity by reducing food intake, increasing the RMR and enhancing fatty acid oxidation.

Keratin-18 and microRNA-122 complement alanine aminotransferase as novel safety biomarkers for drug-induced liver injury in two human cohorts.

BACKGROUND & AIMS: There is a demand for more sensitive, specific and predictive biomarkers for drug-induced liver injury (DILI) than the gold standard used today, alanine aminotransferase (ALT). The aim of this study was to qualify novel DILI biomarkers (keratin-18 markers M65/M30, microRNA-122, glutamate dehydrogenase and alpha-foetoprotein) in human DILI. METHODS: Levels of the novel biomarkers were measured by enzyme-linked immunosorbent assay or real-time quantitative reverse-transcription PCR (qRT-PCR) in two human DILI cohorts: a human volunteer study with acetaminophen and a human immunodeficiency virus (HIV)/tuberculosis (TB) study. RESULTS: In the acetaminophen study, serum M65 and microRNA-122 levels were significantly increased at an earlier time point than ALT. Furthermore, the maximal elevation of M65 and microRNA-122 exceeded the increase in ALT. In the HIV/TB study, all the analysed novel biomarkers increased after 1 week of treatment. In contrast to ALT, the novel biomarkers remained stable in a human cohort with exercise-induced muscular injury. CONCLUSIONS: M65 and microRNA-122 are potential biomarkers of DILI superior to ALT with respect to sensitivity and specificity.

Mobile Health Study Incorporating Novel Fitness Test.

Mobile health (mHealth) is a rapidly expanding field within precision medicine and precision health that provides healthcare support and interventions using mobile technologies, such as smartphones and smartwatches. The growing ubiquity of commercial wireless signals and smartphones allows mHealth technologies to have a substantially broader reach than traditional healthcare networks. My Fitness Counts, a cross-platform My Heart Counts spinout study, is a pioneer cross-platform mHealth study for measuring cardiovascular fitness levels. The study uses Real-World Insights, a platform designed to host mHealth studies. In this paper, we present insights gained through the quality control process undertaken prior to the release of the cross-platform mHealth study My Fitness Counts. Through extensive testing of the 21 iOS and 11 Android builds of the application, over 70 bugs were identified and corrected during the 5-month development process of My Fitness Counts.

Personalized digital behaviour interventions increase short-term physical activity: a randomized control crossover trial substudy of the MyHeart Counts Cardiovascular Health Study.

Aims: Physical activity is associated with decreased incidence of the chronic diseases associated with aging. We previously demonstrated that digital interventions delivered through a smartphone app can increase short-term physical activity. Methods and results: We offered enrolment to community-living iPhone-using adults aged ≥18 years in the USA, UK, and Hong Kong who downloaded the MyHeart Counts app. After completion of a 1-week baseline period, e-consented participants were randomized to four 7-day interventions. Interventions consisted of: (i) daily personalized e-coaching based on the individual's baseline activity patterns, (ii) daily prompts to complete 10 000 steps, (iii) hourly prompts to stand following inactivity, and (iv) daily instructions to read guidelines from the American Heart Association (AHA) website. After completion of one 7-day intervention, participants subsequently randomized to the next intervention of the crossover trial. The trial was completed in a free-living setting, where neither the participants nor investigators were blinded to the intervention. The primary outcome was change in mean daily step count from baseline for each of the four interventions, assessed in a modified intention-to-treat analysis (modified in that participants had to complete 7 days of baseline monitoring and at least 1 day of an intervention to be included in analyses). This trial is registered with ClinicalTrials.gov, NCT03090321. Conclusion: Between 1 January 2017 and 1 April 2022, 4500 participants consented to enrol in the trial (a subset of the approximately 50 000 participants in the larger MyHeart Counts study), of whom 2458 completed 7 days of baseline monitoring (mean daily steps 4232 ± 73) and at least 1 day of one of the four interventions. Personalized e-coaching prompts, tailored to an individual based on their baseline activity, increased step count significantly (+402 ± 71 steps from baseline, P = 7.1⨯10-8). Hourly stand prompts (+292 steps from baseline, P = 0.00029) and a daily prompt to read AHA guidelines (+215 steps from baseline, P = 0.021) were significantly associated with increased mean daily step count, while a daily reminder to complete 10 000 steps was not (+170 steps from baseline, P = 0.11). Digital studies have a significant advantage over traditional clinical trials in that they can continuously recruit participants in a cost-effective manner, allowing for new insights provided by increased statistical power and refinement of prior signals. Here, we present a novel finding that digital interventions tailored to an individual are effective in increasing short-term physical activity in a free-living cohort. These data suggest that participants are more likely to react positively and increase their physical activity when prompts are personalized. Further studies are needed to determine the effects of digital interventions on long-term outcomes.

Alterations in amino acid concentrations in the plasma and muscle in human subjects during 24 h of simulated adventure racing.

This investigation was designed to evaluate changes in plasma and muscle levels of free amino acids during an ultra-endurance exercise and following recovery. Nine male ultra-endurance trained athletes participated in a 24-h standardized endurance trial with controlled energy intake. The participants performed 12 sessions of running, kayaking and cycling (4 × each discipline). Blood samples were collected before, during and after exercise, as well as after 28 h of recovery. Muscle biopsies were taken before the test and after exercise, as well as after 28 h of recovery. During the 24-h exercise, plasma levels of branched-chain (BCAA), essential amino acids (EAA) and glutamine fell 13, 14 and 19% (P < 0.05), respectively, whereas their concentrations in muscle were unaltered. Simultaneously, tyrosine and phenylalanine levels rose 38 and 50% (P < 0.05) in the plasma and 66 and 46% (P < 0.05) in muscle, respectively. After the 24-h exercise, plasma levels of BCAA were positively correlated with muscle levels of glycogen (r (2) = 0.73, P < 0.05), as was the combined concentrations of muscle tyrosine and phenylalanine with plasma creatine kinase (R (2) = 0.55, P < 0.05). Following 28-h of recovery, plasma and muscle levels of amino acids had either returned to their initial levels or were elevated. In conclusion, ultra-endurance exercise caused significant changes elevations in plasma and muscle levels of tyrosine and phenylalanine, which suggest an increase in net muscle protein breakdown during exercise. There was a reduction in plasma concentrations of EAA and glutamine during exercise, whereas no changes were detected in their muscle concentration after exercise.

Rhabdomyolysis/myoglobinemia and NSAID during 48 h ultra-endurance exercise (adventure racing).

Our purpose is to determine whether rhabdomyolysis with myoglobinemia exists during a 48+ h adventure race and if there is a correlation with NSAID use, race time and perceived pain or exertion. Blood samples for analyses of myoglobin (Mb) were collected, and perception of exertion and pain was registered on the Borg-RPE and CR scales, from 20 subjects (3 female, 17 male) Pre-, Mid- and Post-race. Subjects were asked about NSAID use at each sampling and within 12 h pre-race. The result observed was a significant rise in Mb throughout the race, with the NSAID group (n = 6) having significantly lower Mb-Post than the no-NSAID group (n = 14). High Mb-Pre and Post correlated to shorter race time and high Mb-Pre to lower Pain-post. Race time also correlated to NSAID use, with the NSAID group having significantly longer race time than the no-NSAID group. Rhabdomyolysis with myoglobinemia, which might be reduced with NSAID use, exists during a 48+ h adventure race. Indications that high Mb-levels correlate with shorter race time and less pain, and the reasons for the NSAID groups longer race time, warrants further investigation.

Plasma IL-6 concentration during ultra-endurance exercise.

Interleukin 6 (IL-6) response was studied during two ultra endurance events-one laboratory 24 h protocol (9 men) with exercise intensity set to 60% of VO(2max) and one Adventure Race over 6 days (12 men/6 women) with a self-selected race pace, including rests, of about 38% of VO(2max). In the 24-h protocol IL-6 level was elevated from 0.76 ± 0.48 pg mL(-1) at rest to 7.16 ± 2.70 pg mL(-1) at 6 h, and increased further to 10.58 ± 1.04 pg mL(-1) at 12 h, but remained thereafter unchanged at 24 h, (10.89 ± 0.36 pg mL(-1)). All participants had nearly identical values at 12 and 24 h, supporting intensity as main determinant in the IL-6 response during prolonged exercise since exercise duration did not increase IL-6 level after 12 h. Possible confounding factors do not seem to influence the IL-6 concentration during the longer races (>12 h), but might very well do so during shorter exercise bouts. In the 6-day race IL-6 increased from rest to 24 h, but thereafter there was no change in plasma IL-6 value until the end of the race (mean 143.5 h). There was no elevation of TNF-α in any of the protocols, suggesting that the competitors were free from systemic inflammation. We conclude that during endurance exercise lasting >12 h intensity, and not duration, is the main determinant of the IL-6 response, while during shorter exercise bouts both intensity and duration contribute to the accumulation of IL-6 in plasma.

Reversed drift in heart rate but increased oxygen uptake at fixed work rate during 24 h ultra-endurance exercise.

In this paper we report a reversed drift in heart rate (HR) but increased oxygen uptake (VO(2)) during ultra-endurance exercise. Nine well-trained male athletes performed 24-h exercise in a controlled laboratory setting, with alternating blocks of kayaking, running and cycling. Each block included 110 min of exercise and 10 min of rest, with an average work intensity of approximately 55% of respective VO(2peak). Blood samples were taken and HR and VO(2) measured every 6th hour during steady-state cycling at fixed work rate. As assumed HR was increased at 6 h by 15 +/- 6 beats/min compared with initial level (0 h). Thereafter the drift did not progress continuously, but instead unexpectedly returned toward initial values, although the plasma levels of catecholamines increased continuously during exercise. VO(2) was increased by 0.22 +/- 0.15 L/min (10%) at 6 h and 0.37 +/- 0.18 L/min (17%) at 12 h compared with 0 h, and thereafter remained stable. This implies an increased oxygen pulse (VO(2)/HR) by approximately 10% at the last half of the 24-h exercise compared with 0 h. Consequently, sole use of HR would give inaccurate estimates of exercise intensity and energy expenditure during endurance exercise lasting more than 6 h, and different patterns of cardiovascular drift need to be taken into account.

Energy turnover during 24 hours and 6 days of adventure racing.

Energy turnover was assessed in two conditions of mixed ultra-endurance exercise. In Study 1, energy expenditure and intake were measured in nine males in a laboratory over 24 h. In Study 2, energy expenditure was assessed in six males during an 800-km Adventure race (mean race time 152.5 h). Individual correlations between heart rate and oxygen uptake (VO(2)) were established during pre-tests when kayaking, cycling, and running. During exercise, energy expenditure was estimated from continuous heart rate recordings. Heart rate and VO(2) were measured regularly during fixed cycling work rates to correct energy expenditure for drift in oxygen pulse. Mean energy expenditure was 18,050 +/- 2,390 kcal (750 +/- 100 kcal h(-1)) and 80,000 +/- 18,000 kcal (500 +/- 100 kcal h(-1)) in Study 1 and Study 2 respectively, which is higher than previously reported. Energy intake in Study 1 was 8,450 +/- 1,160 kcal, resulting in an energy deficit of 9,590 +/- 770 kcal. Body mass decreased in Study 1 (-2.3 +/- 0.8 kg) but was unchanged in Study 2. Fat mass decreased in Study 2 (-2.3 +/- 1.5 kg). In Study 1, muscle glycogen content decreased by only 60%. Adventure racing requires a high energy expenditure, with large inter-individual variation. A large energy deficit is caused by inadequate energy intake, possibly due to suppressed appetite and gastrointestinal problems. The oxygen pulse, comparing start to 12 h of exercise and beyond, increased by 10% and 5% in Study 1 and Study 2 respectively. Hence, estimations of energy expenditure from heart rate recordings should be corrected according to this drift.

Physiological Factors of Importance for Load Carriage in Experienced and Inexperienced Men and Women.

INTRODUCTION: The ability to carry heavy loads is an important and necessary task during numerous outdoor activities and especially in military operations. The aim of this study was to investigate factors associated with load-carrying ability in men and women with and without extensive load-carrying experience. MATERIALS AND METHODS: The energy expenditure during carrying no load, 20, 35, and 50 kg at 2 walking speeds, 3 and 5 km h-1, was studied in 36 healthy participants, 19 men (30 ± 6 years, 82.5 ± 7.0 kg) and 17 women (29 ± 6 years, 66.1 ± 8.9 kg), experienced (>5 years) in carrying heavy loads (n = 16, 8 women) or with minor or no such experience (n = 20, 9 women). A standard backpack filled with weights to according carry load was used during the walks. Anthropometric data, leg muscle strength, as well as trunk muscle endurance and muscle fiber distribution of the thigh, were also obtained. Extra Load Index (ELI)-the oxygen uptake (VO2) during total load over unloaded walking-was used as a proxy for load-carrying ability at 20, 35, and 50 kg (ELI20, ELI35, and ELI50, respectively). In addition to analyzing factors of importance for the ELI values, we also conducted mediator analyses using sex and long-term carrying experience as causal variables for ELI as the outcome value. The study was approved by the Regional Ethics Committee in Stockholm, Sweden. RESULTS: For the lowest load (20 kg), ELI20, was correlated with body mass but no other factors. Walking with 35 and 50 kg load at 5 km h-1 body mass, body height, leg muscle strength, and absolute VO2max were correlated, while relative VO2max, trunk muscle endurance, and leg muscle fiber distribution were not correlated to ELI35 and ELI50.ELI50 at 5 km h-1 differed between the sexes. This difference was only mediated by the difference in body mass. Neither muscle fiber distribution, leg muscle strength, trunk muscle endurance, and body height nor did absolute or relative VO2max explain the difference.Participants with long-term experience of heavy load carrying had significant lower ELI20 and ELI50 values than those with minor or no experience, but none of the above studied factors could explain this difference. CONCLUSION: The study showed that body mass, without sex differences, and experience of carrying heavy loads are the dominant factors for the ability to carry heavy loads. Even though the effect of experience alludes to the need for extensive carrying training, no causality can be proven. Load carry training intervention studies is suggested for future investigations.

Performance and cardiac evaluation before and after a 3-week training camp for 400-meter sprinters - An observational, non-randomized study.

OBJECTIVE: To study the performance and cardiovascular function after a 3-week training camp in athletes competing in an anaerobically dominant sport. METHODS: Twenty-three competitive 400-m athletes were enrolled in this non-randomized study, 17 took part in a 3-week training camp in South-Africa (intervention), but one declined follow-up assessment, while 6 pursued in-door winter training in Sweden and served as controls. Electrocardiography, transthoracic echocardiography, blood test analyses, maximal exercise tolerance test, and a 300-m sprint test with lactate measurements ([La]peak) were performed before and after the training camp period. RESULTS: At baseline, there were no clinically significant pathological findings in any measurements. The training period resulted in improved 300m-sprint performance [n = 16; running time 36.71 (1.39) vs. 35.98 (1.13) s; p<0.01] and higher peak lactate values. Despite 48% more training sessions than performed on home ground (n = 6), myocardial biomarkers decreased significantly (NT-pro BNP -38%; p<0.05, troponin T -16%; p<0.05). Furthermore, resting heart rate (-7%; p<0.01) and left ventricular systolic and diastolic volumes decreased -6% (p<0.01) and -10% (p<0.05), respectively. CONCLUSIONS: Intense physical activity at training camp improved the performance level, likely due to improved anaerobic capacity indicated by higher [La]peak. There were no clinically significant adverse cardiac changes after this period of predominantly anaerobic training.

SR Ca2+ leak in skeletal muscle fibers acts as an intracellular signal to increase fatigue resistance.

Effective practices to improve skeletal muscle fatigue resistance are crucial for athletes as well as patients with dysfunctional muscles. To this end, it is important to identify the cellular signaling pathway that triggers mitochondrial biogenesis and thereby increases oxidative capacity and fatigue resistance in skeletal muscle fibers. Here, we test the hypothesis that the stress induced in skeletal muscle fibers by endurance exercise causes a reduction in the association of FK506-binding protein 12 (FKBP12) with ryanodine receptor 1 (RYR1). This will result in a mild Ca2+ leak from the sarcoplasmic reticulum (SR), which could trigger mitochondrial biogenesis and improved fatigue resistance. After giving mice access to an in-cage running wheel for three weeks, we observed decreased FKBP12 association to RYR1, increased baseline [Ca2+]i, and signaling associated with greater mitochondrial biogenesis in muscle, including PGC1α1. After six weeks of voluntary running, FKBP12 association is normalized, baseline [Ca2+]i returned to values below that of nonrunning controls, and signaling for increased mitochondrial biogenesis was no longer present. The adaptations toward improved endurance exercise performance that were observed with training could be mimicked by pharmacological agents that destabilize RYR1 and thereby induce a modest Ca2+ leak. We conclude that a mild RYR1 SR Ca2+ leak is a key trigger for the signaling pathway that increases muscle fatigue resistance.

The use of the Chandler loop to examine the interaction potential of NXY-059 on the thrombolytic properties of rtPA on human thrombi in vitro.

BACKGROUND AND PURPOSE: Recombinant tissue-type plasminogen activator (rtPA) is the only globally approved treatment for acute ischaemic stroke. Other potential treatments might be administered with rtPA, making it important to discover whether compounds interfere with rtPA-induced lysis. We evaluated methods for examining the effect of the neuroprotectant NXY-059 on the lytic property of rtPA. EXPERIMENTAL APPROACH: Plasma clot formation and lysis in the presence of rtPA and NXY-059 was measured as the change in plasma turbidity. The effect of NXY-059 on rtPA-induced lysis was similarly assessed on preformed clots. Lysis of the thrombus formed in a Chandler loop measured release of fluorescent-tagged fibrinogen that had been incorporated during thrombus formation. Thrombi were exposed to both rtPA and NXY-059 throughout lysis in the presence of 80% autologous plasma and the release of label during lysis was measured. KEY RESULTS: Data interpretation is limited in the clot lysis experiments because either the rtPA was present during clot formation or the drug was added to a clot formed in static conditions. In contrast, thrombi were formed in dynamic flow conditions in the Chandler loop and the time course of lysis in plasma was examined. rtPA increased thrombolysis and the antifibrinolytic trans-4-(aminomethyl) cyclohexane carboxylic acid (AMCA) inhibited lysis. Lysis induced by rtPA was unaltered by NXY-059. CONCLUSIONS AND IMPLICATIONS: The Chandler loop method provides a reliable technique for examining the effect of compounds on rtPA-induced lysis in vitro and demonstrated that NXY-059 does not alter rtPA-induced lysis at clinically relevant concentrations of either drug.

Lack of sex differences in the IGF-IGFBP response to ultra endurance exercise.

The insulin-like growth factor (IGF)-IGF binding proteins (BP) and the pituitary-gonadal axes were investigated during ultra endurance exercise in 16 endurance-trained athletes (seven women). Median duration of the race was 6.3 days. Although food and drink were ad libitum, energy balance was negative. Blood samples were drawn before (PRE), at the end of (END) and 24 h after (POST24h) the race. Serum concentrations of total IGF-I (t-IGF-I) and free IGF-I (f-IGF-I) decreased by 33 (SD 38)% and 54 (19)%, respectively. The decrease in t-IGF-I appeared to be associated to the total energy deficit during the race. At END, the IGFBP-3 fragmentation and IGFBP-1 were increased but these changes did not predict changes in f-IGF-I. An increase in POST24h IGFBP-2 levels in women was the only sex difference. Testosterone was decreased by 67 (12)% in the men and estradiol became undetectable in the women without any detectable increase in LH and/or FSH. In conclusion ultra endurance exercise results in similar IGF-IGFBP responses in men and women reflecting a catabolic state. IGFBP-2 was the only exception, with increased levels in women after exercise. A concomitant decrease in gonadal hormones was not related to endocrine changes in the IGF-IGFBP axis but may be related to local changes in IGF-I expression.

Effects of Flywheel Training on Strength-Related Variables: a Meta-analysis.

BACKGROUND: Strength and power development are abilities important for athletic performance in many sports. Generally, resistance training based on gravity is used to improve these qualities. Flywheel training instead utilizes kinetic energy transferred to a flywheel. This allows for eccentric overload and variable resistance throughout the movement. The aim of this review was to identify the effects of flywheel training on multiple strength-related variables affecting athletic performance. The meta-analysis investigates the effects on (1) muscle growth (cross-sectional area (CSA) and volume/mass), (2) maximum dynamic strength, (3) development of power, (4) development of horizontal movement, and (5) development of vertical movement. METHODS: The meta-analysis includes 20 experimental studies that met the inclusion criteria. The quality of included studies was ranked according to the PEDro scale. Possible bias was identified in Funnel plot analyses. To enable the compilation of all results analyses, the random effect model was carried out using the software Review Manager Version 5.3 and presented with Forest plots. RESULTS: Flywheel training for a period of 4-24 weeks shows statistically significant increases in all strength aspects. Effect sizes were for hypertrophy, CSA 0.59; volume/mass 0.59; maximum strength 1.33; power 1.19; horizontal 1.01 and vertical movement 0.85. The evidence is particularly strong for beneficial effects from flywheel training in the development of maximal strength and power in trained younger individuals, and utilization of this training modality in shorter more intensive blocks. CONCLUSIONS: Flywheel training is an effective method for improving several aspects of strength and power with importance for sports performance.

Antithrombotic properties in rabbits of heparin and heparin fragments covalently coupled to human antithrombin III.

Clinical grade heparin is a very heterogeneous mucopolysaccharide, containing molecules with Mr ranging from 6,000 to 30,000 that have either a high affinity or a low affinity for antithrombin III (AT). In this study, the antithrombotic properties of intact high-affinity heparin (Mr = 15,000) and of two heparin fragments (h16, a 16-monosaccharide fragment, with Mr = 4,300, and h12, a 12-monosaccharide fragment, with Mr = 3,200) and of their functional covalent stoichiometric complexes with human AT were compared in a venous thrombosis stasis model in rabbits. Thrombosis was induced by injection of glass-activated human plasma and measured in a segment of the jugular vein that was isolated between two vascular clamps for 10 min. Injections of 55 micrograms/kg resulted in a clear antithrombotic effect for intact heparin, but not for the two fragments. Equivalent amounts (carbohydrate moiety) of covalent complexes of heparin or of both heparin fragments with human AT resulted in an antithrombotic effect lasting for 45-60 min. Injection of 110 micrograms/kg of heparin and of the heparin fragments yielded an antithrombotic effect, lasting 45-60 min; the corresponding amounts of covalent complexes caused an anti-thrombotic effect for 60-120 min. The free and conjugated fragments produced equal antithrombotic effects at equal plasma levels of anti-Factor Xa activity, but the specific antithrombotic activities of free and complexed intact heparin, on a molar basis, were 10-20-fold greater than those of the free and complexed heparin fragments. The plasma half-life of the covalent complexes of the heparin fragments with AT is, however, 10 times longer than that of the complex between intact heparin and AT and 30 times longer than that of free intact heparin. Covalent complexes between AT and heparin fragments could, therefore, be useful to maintain more stable levels of antithrombotic activity in plasma.

Reduced efficiency, but increased fat oxidation, in mitochondria from human skeletal muscle after 24-h ultraendurance exercise.

The hypothesis that ultraendurance exercise influences muscle mitochondrial function has been investigated. Athletes in ultraendurance performance performed running, kayaking, and cycling at 60% of their peak O(2) consumption for 24 h. Muscle biopsies were taken preexercise (Pre-Ex), postexercise (Post-Ex), and after 28 h of recovery (Rec). Respiration was analyzed in isolated mitochondria during state 3 (coupled to ATP synthesis) and state 4 (noncoupled respiration), with fatty acids alone [palmitoyl carnitine (PC)] or together with pyruvate (Pyr). Electron transport chain activity was measured with NADH in permeabilized mitochondria. State 3 respiration with PC increased Post-Ex by 39 and 41% (P < 0.05) when related to mitochondrial protein and to electron transport chain activity, respectively. State 3 respiration with Pyr was not changed (P > 0.05). State 4 respiration with PC increased Post-Ex but was lower than Pre-Ex at Rec (P < 0.05 vs. Pre-Ex). Mitochondrial efficiency [amount of added ADP divided by oxygen consumed during state 3 (P/O ratio)] decreased Post-Ex by 9 and 6% (P < 0.05) with PC and PC + Pyr, respectively. P/O ratio remained reduced at Rec. Muscle uncoupling protein 3, measured with Western blotting, was not changed Post-Ex but tended to decrease at Rec (P = 0.07 vs. Pre-Ex). In conclusion, extreme endurance exercise decreases mitochondrial efficiency. This will increase oxygen demand and may partly explain the observed elevation in whole body oxygen consumption during standardized exercise (+13%). The increased mitochondrial capacity for PC oxidation indicates plasticity in substrate oxidation at the mitochondrial level, which may be of advantage during prolonged exercise.

Regular moist snuff dipping does not affect endurance exercise performance.

Physiological and medical effects of snuff have previously been obtained either in cross-sectional studies or after snuff administration to non-tobacco users. The effects of snuff cessation after several years of daily use are unknown. 24 participants with >2 years of daily snuff-use were tested before and after >6 weeks snuff cessation (SCG). A control group (CO) of 11 snuff users kept their normal habits. Resting heart rate (HR) and blood pressure (BP) were significantly lower in SCG after snuff cessation, and body mass was increased by 1.4 ± 1.7 kg. Total cholesterol increased from 4.12 ± 0.54 (95% CI 3.89-4.35) to 4.46 ± 0.70 (95% CI 4.16-4.75) mM L-1 in SCG, due to increased LDL, and this change was significantly different from CO. Resting values of HDL, C-reactive protein, and free fatty acids (FFA) remained unchanged in both groups. In SCG group, both HR and BP were reduced during a four-stage incremental cycling test (from 50 to 80% of VO2max) and a prolonged cycling test (60 min at 50% of VO2max). Oxygen uptake (VO2), respiratory exchange ratio, blood lactate (bLa) and blood glucose (bGlu) concentration, and rate of perceived exertion (RPE) were unchanged. In CO group, all measurements were unchanged. During the prolonged cycling test, FFA was reduced, but with no significant difference between groups. During the maximal treadmill running test peak values of VO2, pulmonary ventilation (VE), time to exhaustion and bLa were unchanged in both groups. In conclusion, endurance exercise performance (VO2max and maximal endurance time) does not seem to be affected by prolonged snuff use, while effects on cardiovascular risk factors are contradictory. HR and BP during rest and submaximal exercise are reduced after cessation of regular use of snuff. Evidently, the long-time adrenergic stress on circulation is reversible.