Similar improvements in 5-km performance and maximal oxygen uptake with submaximal and maximal 10-20-30 training in runners, but increase in muscle oxidative phosphorylation occur only with maximal effort training.

OBJECTIVE: The aim of the present study was to examine whether 10-20-30 training (consecutive 1-min intervals consisting of 30 s at low-speed, 20 s at moderate-speed, and 10 s at high-speed), performed with submaximal effort during the 10-s high-speed runs, would lead to improved performance as well as increased maximum oxygen uptake (VO2 -max) and muscle oxidative phosphorylation (OXPHOS). In addition, to examine to what extent the effects would compare to 10-20-30 running conducted with maximal effort. DESIGN: Nineteen males were randomly assigned to 10-20-30 running performed with either submaximal (SUBMAX; n = 11) or maximal (MAX; n = 8) effort, which was conducted three times/week for 6 weeks (intervention; INT). Before and after INT, subjects completed a 5-km running test and a VO2 -max test, and a biopsy was obtained from m. vastus lateralis. RESULTS: After compared to before INT, SUBMAX and MAX improved (p < 0.05) 5-km performance by 3.0% (20.8 ± 0.4 (means±SE) vs. 21.5 ± 0.4 min) and 2.3% (21.2 ± 0.4 vs. 21.6 ± 0.4 min), respectively, and VO2 -max was ~7% higher (p < 0.01) in both SUBMAX (57.0 ± 1.3 vs. 53.5 ± 1.1 mL/min/kg) and MAX (57.8 ± 1.2 vs. 53.7 ± 0.9 mL/min/kg), with no difference in the changes between groups. In SUBMAX, muscle OXPHOS was unchanged, whereas in MAX, muscle OXPHOS subunits (I-IV) and total OXPHOS (5.5 ± 0.3 vs 4.7 ± 0.3 A.U.) were 9%-29% higher (p < 0.05) after compared to before INT. CONCLUSION: Conducting 10-20-30 training with a non-maximal effort during the 10-s high-speed runs is as efficient in improving 5-km performance and VO2 -max as maximal effort exercise, whereas increase in muscle OXPHOS occur only when the 10-s high-speed runs are performed with maximal effort.

Inhaled beta2 -agonist, formoterol, enhances intense exercise performance, and sprint ability in elite cyclists.

PURPOSE: Many athletes use long-acting beta2 -agonist formoterol in treatment of asthma. However, studies in non-athlete cohorts demonstrate that inhaled formoterol can enhance sprint performance calling into question whether its use in competitive sports should be restricted. We investigated whether formoterol at upper recommended inhaled doses (54 µg) would enhance sprint ability and intense exercise performance in elite cyclists. METHODS: Twenty-one male cyclists (V̇O2max : 70.4 ± 4.3 mL × min-1 × kg-1 , mean ± SD) completed two 6-s all-out sprints followed by 4-min all-out cycling after inhaling either 54 µg formoterol or placebo. We also assessed cyclists' leg muscle mass by dual-energy X-ray absorptiometry and muscle fiber type distribution of vastus lateralis biopsies. RESULTS: Peak and mean power output during the 6-s sprint was 32 W (95% CI, 19-44 W, p < 0.001) and 36 W (95% CI, 24-48 W, p < 0.001) higher with formoterol than placebo, corresponding to an enhancing effect of around 3%. Power output during 4-min all-out cycling was 9 W (95% CI, 2-16 W, p = 0.01) greater with formoterol than placebo, corresponding to an enhancing effect of 2.3%. Performance changes in response to formoterol were unrelated to cyclists' VO2max and leg lean mass, whereas muscle fiber Type I distribution correlated with change in sprinting peak power in response to formoterol (r2 = 0.314, p = 0.012). CONCLUSION: Our findings demonstrate that an inhaled one-off dose of 54 µg formoterol has a performance-enhancing potential on sprint ability and short intense performance in elite male cyclists, which is irrespective of training status but partly related to muscle fiber type distribution for sprint ability.

No additive effect of creatine, caffeine, and sodium bicarbonate on intense exercise performance in endurance-trained individuals.

BACKGROUND: Athletes commonly use creatine, caffeine, and sodium bicarbonate for performance enhancement. While their isolated effects are well-described, less is known about their potential additive effects. METHODS: Following a baseline trial, we randomized 12 endurance-trained males (age: 25 ± 5 years, VO2max: 56.7 ± 4.6 mL kg-1 min-1; mean ± SD) and 11 females (age: 25 ± 3 years, VO2max: 50.2 ± 3.4 mL kg-1 min-1) to 5 days of creatine monohydrate (0.3 g kg-1 per day) or placebo loading, followed by a daily maintenance dose (0.04 g kg-1) throughout the study. After the loading period, subjects completed four trials in randomized order where they ingested caffeine (3 mg kg-1), sodium bicarbonate (0.3 g kg-1), placebo, or both caffeine and sodium bicarbonate before a maximal voluntary contraction (MVC), 15-s sprint, and 6-min time trial. RESULTS: Compared to placebo, mean power output during 15-s sprint was higher following loading with creatine than placebo (+34 W, 95% CI: 10 to 58, p = 0.008), but with no additional effect of caffeine (+10 W, 95% CI: -7 to 24, p = 0.156) or sodium bicarbonate (+5 W, 95% CI: -4 to 13, p = 0.397). Mean power output during 6-min time trial was higher with caffeine (+12 W, 95% CI: 5 to 18, p = 0.001) and caffeine + sodium bicarbonate (+8 W, 95% CI: 0 to 15, p = 0.038), whereas sodium bicarbonate (-1 W, 95% CI: -7 to 6, p = 0.851) and creatine (-6 W, 95% CI: -15 to 4, p = 0.250) had no effects. CONCLUSION: While creatine and caffeine can enhance sprint- and time trial performance, respectively, these effects do not seem additive. Therefore, supplementing with either creatine or caffeine appears sufficient to enhance sprint or short intense exercise performance.

Importance of training volume during intensified training in elite cyclists: Maintained vs. reduced volume at moderate intensity.

INTRODUCTION: Male elite cyclists (average VO2 -max: 71 mL/min/kg, n = 18) completed 7 weeks of high-intensity interval training (HIT) (3×/week; 4-min and 30-s intervals) during the competitive part of the season. The influence of a maintained or lowered total training volume combined with HIT was evaluated in a two-group design. Weekly moderate-intensity training was lowered by ~33% (~5 h) (LOW, n = 8) or maintained at normal volume (NOR, n = 10). Endurance performance and fatigue resistance were evaluated via 400 kcal time-trials (~20 min) commenced either with or without prior completion of a 120-min preload (including repeated 20-s sprints to simulate physiologic demands during road races). RESULTS: Time-trial performance without preload was improved after the intervention (p = 0.006) with a 3% increase in LOW (p = 0.04) and a 2% increase in NOR (p = 0.07). Preloaded time-trial was not significantly improved (p = 0.19). In the preload, average power during repeated sprinting increased by 6% in LOW (p < 0.01) and fatigue resistance in sprinting (start vs end of preload) was improved (p < 0.05) in both groups. Blood lactate during the preload was lowered (p < 0.001) solely in NOR. Measures of oxidative enzyme activity remained unchanged, whereas the glycolytic enzyme PFK increased by 22% for LOW (p = 0.02). CONCLUSION: The present study demonstrates that elite cyclists can benefit from intensified training during the competitive season both with maintained and lowered training volume at moderate intensity. In addition to benchmarking the effects of such training in ecological elite settings, the results also indicate how some performance and physiological parameters may interact with training volume.

Exercise training induces thrombogenic benefits in recent but not late postmenopausal females.

Although regular physical activity is known to improve cardiovascular health in men, evidence for its beneficial effects in postmenopausal females is less convincing and it remains unclear whether initiation of exercise training soon after, rather than many years after menopause impacts the magnitude of training-induced adaptations. We evaluated exercise-induced changes in markers of thrombotic risk and conduit artery function in recent≤5yr compared with late≥10yr postmenopausal females. Fourteen recent≤5yr and 13 late≥10yr healthy postmenopausal females completed 8 wk of regular intensive exercise training, consisting of floorball and cycling. Markers of thrombotic risk and vascular health were assessed before and after the intervention, and data were analyzed using a linear mixed model. Exercise training reduced markers of thrombotic risk, including an 11% reduction (P = 0.007) in agonist-induced platelet reactivity and a reduction (P = 0.027) in incipient clot microstructure (∼40% reduction in clot mass) in the recent≤5yr but not the late≥10yr (P = 0.380; P = 0.739, respectively) postmenopausal females. There was no change in conduit artery function, as measured by brachial (recent≤5yr, P = 0.804; late≥10yr, P = 0.311) and popliteal artery (recent≤5yr, P = 0.130; late≥10yr, P = 0.434) flow-mediated dilation. Only the late≥10yr postmenopausal females exhibited an increase (by 9.6%, P = 0.022) in intracellular adhesion molecule-1 levels after training, which may have impacted the thrombogenic adaptation in this group. These findings suggest that 8 wk of high-intensity exercise training reduces thrombotic risk in recent≤5yr, but not late≥10yr postmenopausal females. Thus, regular physical activity initiated soon after, rather than many years after menopause and at a higher age, may be more efficient for reducing thrombogenic risk.NEW & NOTEWORTHY Eight weeks of high-intensity exercise training reduces platelet reactivity as well as blood clot density and strength in females ≤5 yr past menopause but not in females ≥10 yr past menopause. The divergent response in the late postmenopausal females may be explained by training-induced low-grade systemic inflammation. These findings suggest that regular physical activity initiated soon after menopause, compared with many years after menopause, may be more efficient for reducing the risk of blood clots.

Effect of sample fractionation and normalization when immunoblotting for human muscle Na+/K+-ATPase subunits and glycogen synthase.

Immunoblotting is widely used in muscle physiology to determine protein regulation and abundance. However, research groups use different protocols, which may result in differential outcomes. Herein, we investigated the effect of various homogenization procedures on determination of protein abundance in human m. vastus lateralis biopsies. Furthermore, we investigated differences in abundance between young healthy males (n = 12) and type-2 diabetics (n = 4), and the effect of data normalization. Fractionated lysates had the lowest variation in total protein determination as compared to non-fractionated homogenates. Abundance of NKAα2, NKAß1, FXYD1, and glycogen synthase was higher (P < 0.05) in young healthy than in type-2 diabetics determined in both fractionated and non-fractionated samples for which normalization to the stain-free signal and/or standard curve did not affect outcomes. Precision and reliability of protein abundance determination between sample types showed a moderate to good reliability for these proteins, whereas the commonly used house-keeping protein, actin, showed poor reliability. In conclusion, fractionated and non-fractionated immunoblotting samples yield similar data for several sarcolemmal and cytosolic proteins, except for actin, which, therefore appears inappropriate for data normalization in immunoblotting of human skeletal muscle. Thus, fractionation does not seem to be a major source of bias when immunoblotting for NKA subunits and GS.

High-Intensity Training Represses FXYD5 and Glycosylates Na,K-ATPase in Type II Muscle Fibres, Which Are Linked with Improved Muscle K+ Handling and Performance.

Na+/K+ ATPase (NKA) comprises several subunits to provide isozyme heterogeneity in a tissue-specific manner. An abundance of NKA α, ß, and FXYD1 subunits is well-described in human skeletal muscle, but not much is known about FXYD5 (dysadherin), a regulator of NKA and ß1 subunit glycosylation, especially with regard to fibre-type specificity and influence of sex and exercise training. Here, we investigated muscle fibre-type specific adaptations in FXYD5 and glycosylated NKAß1 to high-intensity interval training (HIIT), as well as sex differences in FXYD5 abundance. In nine young males (23.8 ± 2.5 years of age) (mean ± SD), 3 weekly sessions of HIIT for 6 weeks enhanced muscle endurance (220 ± 102 vs. 119 ± 99 s, p < 0.01) and lowered leg K+ release during intense knee-extensor exercise (0.5 ± 0.8 vs. 1.0 ± 0.8 mmol·min-1, p < 0.01) while also increasing cumulated leg K+ reuptake 0-3 min into recovery (2.1 ± 1.5 vs. 0.3 ± 0.9 mmol, p < 0.01). In type IIa muscle fibres, HIIT lowered FXYD5 abundance (p < 0.01) and increased the relative distribution of glycosylated NKAß1 (p < 0.05). FXYD5 abundance in type IIa muscle fibres correlated inversely with the maximal oxygen consumption (r = -0.53, p < 0.05). NKAα2 and ß1 subunit abundances did not change with HIIT. In muscle fibres from 30 trained males and females, we observed no sex (p = 0.87) or fibre type differences (p = 0.44) in FXYD5 abundance. Thus, HIIT downregulates FXYD5 and increases the distribution of glycosylated NKAß1 in type IIa muscle fibres, which is likely independent of a change in the number of NKA complexes. These adaptations may contribute to counter exercise-related K+ shifts and enhance muscle performance during intense exercise.

Muscle hypertrophic effect of inhaled beta2 -agonist is associated with augmented insulin-stimulated whole-body glucose disposal in young men.

Rodent studies highlight enhancement of glucose tolerance and insulin sensitivity as potential clinically relevant effects of chronic beta2 -agonist treatment. However, the doses administered to rodents are not comparable with the therapeutic doses used for humans. Thus, we investigated the physiological effects of prolonged beta2 -agonist treatment at inhaled doses resembling those used in respiratory diseases on insulin-stimulated whole-body glucose disposal and putative mechanisms in skeletal muscle and adipose tissue of healthy men. Utilizing a randomized placebo-controlled parallel-group design, we assigned 21 healthy men to 4 weeks daily inhalation of terbutaline (TER; 4 mg × day-1 , n = 13) or placebo (PLA, n = 8). Before and after treatments, we assessed subjects' whole-body insulin-stimulated glucose disposal and body composition, and collected vastus lateralis muscle and abdominal adipose tissue biopsies. Glucose infusion rate increased by 27% (95% CI: 80 to 238 mg × min-1 , P = 0.001) in TER, whereas no significant changes occurred in PLA (95% CI: -37 to 195 mg × min-1 , P = 0.154). GLUT4 content in muscle or adipose tissue did not change, nor did hexokinase II content or markers of mitochondrial volume in muscle. Change in lean mass was associated with change in glucose infusion rate in TER (r = 0.59, P = 0.03). Beta2 -agonist treatment in close-to-therapeutic doses may augment whole-body insulin-stimulated glucose disposal in healthy young men and part of the change is likely to be explained by muscle hypertrophy. These findings highlight the therapeutic potential of beta2 -agonists for improving insulin sensitivity. KEY POINTS: While studies in rodents have highlighted beta2 -agonists as a means to augment insulin sensitivity, these studies utilized beta2 -agonists at doses inapplicable to humans. Herein we show that a 4-week treatment period with daily therapeutic inhalation of beta2 -agonist increases insulin-stimulated whole-body glucose disposal in young healthy lean men. This effect was associated with an increase of lean mass but not with changes in GLUT4 and hexokinase II or basal glycogen content in skeletal muscle nor GLUT4 content in abdominal adipose tissue. These findings suggest that the enhanced insulin-stimulated whole-body glucose disposal induced by a period of beta2 -agonist treatment in humans, at least in part, is attributed to muscle hypertrophy. Our observations extend findings in rodents and highlight the therapeutic potential of beta2 -agonists to enhance the capacity for glucose disposal and whole-body insulin sensitivity, providing important knowledge with potential application in insulin resistance.

Beta2 -agonist increases skeletal muscle interleukin 6 production and release in response to resistance exercise in men.

OBJECTIVE: Several tissues produce and release interleukin-6 (IL-6) in response to beta2 -adrenergic stimulation with selective agonists (beta2 -agonists). Moreover, exercise stimulates muscle IL-6 production, but whether beta2 -agonists regulate skeletal muscle production and release of IL-6 in humans in association with exercise remains to be clarified. Thus, we investigated leg IL-6 release in response to beta2 -agonist salbutamol in lean young men at rest and in recovery from resistance exercise. DESIGN: The study employed a randomized controlled crossover design, where 12 men ingested either salbutamol (16 mg) or placebo for 4 days, followed by the last dose (24 mg) administered 1½ h before exercise. Arterial and femoral venous plasma IL-6 as well as femoral artery blood flow was measured before and ½-5 h in recovery from quadriceps muscle resistance exercise. Furthermore, vastus lateralis muscle biopsies were collected ½ and 5 h after exercise for determination of mRNA levels of IL-6 and Tumor Necrosis Factor (TNF)-α. RESULTS: Average leg IL-6 release was 1.7-fold higher (p = 0.01) for salbutamol than placebo, being 138 ± 76 and 79 ± 66 pg min-1 (mean ± SD) for salbutamol and placebo, respectively, but IL-6 release was not significantly different between treatments within specific sampling points at rest and after exercise. Muscle IL-6 mRNA was 1.5- and 1.7-fold higher (p = 0.001) for salbutamol than placebo ½ and 5 h after exercise, respectively, whereas no significant treatment differences were observed for TNF-α mRNA. CONCLUSIONS: Beta2 -adrenergic stimulation with high doses of the selective beta2 -agonist salbutamol, preceeded by 4 consecutive daily doses, induces transcription of IL-6 in skeletal muscle in response to resistance exercise, and increases muscle IL-6 release in lean individuals.

Nitrate-rich beetroot juice ingestion reduces skeletal muscle O2 uptake and blood flow during exercise in sedentary men.

Dietary nitrate supplementation has been shown to reduce pulmonary O2 uptake during submaximal exercise and enhance exercise performance. However, the effects of nitrate supplementation on local metabolic and haemodynamic regulation in contracting human skeletal muscle remain unclear. To address this, eight healthy young male sedentary subjects were assigned in a randomized, double-blind, crossover design to receive nitrate-rich beetroot juice (NO3, 9 mmol) and placebo (PLA) 2.5 h prior to the completion of a double-step knee-extensor exercise protocol that included a transition from unloaded to moderate-intensity exercise (MOD) followed immediately by a transition to intense exercise (HIGH). Compared with PLA, NO3 increased plasma levels of nitrate and nitrite. During MOD, leg V̇O2 and leg blood flow (LBF) were reduced to a similar extent (∼9%-15%) in NO3. During HIGH, leg V̇O2 was reduced by ∼6%-10% and LBF by ∼5%-9% (did not reach significance) in NO3. Leg V̇O2 kinetics was markedly faster in the transition from passive to MOD compared with the transition from MOD to HIGH both in NO3 and PLA with no difference between PLA and NO3. In NO3, a reduction in nitrate and nitrite concentration was detected between arterial and venous samples. No difference in the time to exhaustion was observed between conditions. In conclusion, elevation of plasma nitrate and nitrate reduces leg skeletal muscle V̇O2 and blood flow during exercise. However, nitrate supplementation does not enhance muscle V̇O2 kinetics during exercise, nor does it improve time to exhaustion when exercising with a small muscle mass. KEY POINTS: Dietary nitrate supplementation has been shown to reduce systemic O2 uptake during exercise and improve exercise performance. The effects of nitrate supplementation on local metabolism and blood flow regulation in contracting human skeletal muscle remain unclear. By using leg exercise engaging a small muscle mass, we show that O2 uptake and blood flow are similarly reduced in contracting skeletal muscle of humans during exercise. Despite slower V̇O2 kinetics in the transition from moderate to intense exercise, no effects of nitrate supplementation were observed for V̇O2 kinetics and time to exhaustion. Nitrate and nitrite concentrations are reduced across the exercising leg, suggesting that these ions are extracted from the arterial blood by contracting skeletal muscle.

Essential hypertension is associated with blunted smooth muscle cell vasodilator responsiveness and is reversed by 10-20-30 training in men.

Essential hypertension is associated with impairments in vascular function and sympathetic nerve hyperactivity; however, the extent to which the lower limbs are affected remains unclear. We examined the leg vascular responsiveness to infusion of acetylcholine (ACh), sodium nitroprusside (SNP), and phenylephrine (PEP) in 10 hypertensive men [HYP: age 59.5 ± 9.7 (means ± SD) yr; clinical and nighttime blood pressure: 142 ± 10/86 ± 10 and 141 ± 11/83 ± 6 mmHg, respectively; and body mass index (BMI): 29.2 ± 4.0 kg/m2] and 8 age-matched normotensive counterparts (NORM: age 57.9 ± 10.8 yr; clinical and nighttime blood pressure: 128 ± 9/78 ± 7 and 116 ± 3/69 ± 3 mmHg, respectively; and BMI: 26.3 ± 3.1 kg/m2). The vascular responsiveness was evaluated before and after 6 wk of 10-20-30 training, consisting of 3 × 5 × 10-s sprint followed by 30 and 20 s of low- to moderate-intensity cycling, respectively, interspersed by 3 min of rest. Before training, the vascular responsiveness to infusion of SNP was lower (P < 0.05) in HYP compared with NORM, with no difference in the responsiveness to infusion of ACh and PEP. The vascular responsiveness to infusion of SNP and ACh improved (P < 0.05) with training in HYP, with no change in NORM. With training, intra-arterial systolic blood pressure decreased (P < 0.05) by 9 mmHg in both HYP and NORM whereas diastolic blood pressure decreased (5 mmHg; P < 0.05) in HYP only. We provide here the first line of evidence in humans that smooth muscle cell vasodilator responsiveness is blunted in the lower limbs of hypertensive men. This impairment can be reversed by 10-20-30 training, which is an effective intervention to improve the responsiveness of smooth muscle cells in men with essential hypertension.

Training with blood flow restriction increases femoral artery diameter and thigh oxygen delivery during knee-extensor exercise in recreationally trained men.

KEY POINTS: Endurance-type training with blood flow restriction (BFR) increases maximum oxygen uptake ( V̇O2max ) and exercise endurance of humans. However, the physiological mechanisms behind this phenomenon remain uncertain. In the present study, we show that BFR-interval training reduces the peripheral resistance to oxygen transport during dynamic, submaximal exercise in recreationally-trained men, mainly by increasing convective oxygen delivery to contracting muscles. Accordingly, BFR-training increased oxygen uptake by, and concomitantly reduced net lactate release from, the contracting muscles during relative-intensity-matched exercise, at the same time as invoking a similar increase in diffusional oxygen conductance compared to the training control. Only BFR-training increased resting femoral artery diameter, whereas increases in oxygen transport and uptake were dissociated from changes in the skeletal muscle content of mitochondrial electron-transport proteins. Thus, physically trained men benefit from BFR-interval training by increasing leg convective oxygen transport and reducing lactate release, thereby improving the potential for increasing the percentage of V̇O2max that can be sustained throughout exercise. ABSTRACT: In the present study, we investigated the effect of training with blood flow restriction (BFR) on thigh oxygen transport and uptake, and lactate release, during exercise. Ten recreationally-trained men (50 ± 5 mL kg-1  min-1 ) completed 6 weeks of interval cycling with one leg under BFR (BFR-leg; pressure: ∼180 mmHg) and the other leg without BFR (CON-leg). Before and after the training intervention (INT), thigh oxygen delivery, extraction, uptake, diffusion capacity and lactate release were determined during knee-extensor exercise at 25% incremental peak power output (iPPO) (Ex1), followed by exercise to exhaustion at 90% pre-training iPPO (Ex2), by measurement of femoral-artery blood flow and femoral-arterial and -venous blood sampling. A muscle biopsy was obtained from legs before and after INT to determine mitochondrial electron-transport protein content. Femoral-artery diameter was also measured. In the BFR-leg, after INT, oxygen delivery and uptake were higher, and net lactate release was lower, during Ex1 (vs. CON-leg; P < 0.05), with an 11% larger increase in workload (vs. CON-leg; P < 0.05). During Ex2, after INT, oxygen delivery was higher, and oxygen extraction was lower, in the BFR-leg compared to the CON-leg (P < 0.05), resulting in an unaltered oxygen uptake (vs. CON-leg; P > 0.05). In the CON-leg, at both intensities, oxygen delivery, extraction, uptake and lactate release remained unchanged (P > 0.05). Resting femoral artery diameter increased with INT only in the BFR-leg (∼4%; P < 0.05). Oxygen diffusion capacity was similarly raised in legs (P < 0.05). Mitochondrial protein content remained unchanged in legs (P > 0.05). Thus, BFR-interval training enhances oxygen utilization by, and lowers lactate release from, submaximally-exercising muscles of recreationally-trained men mainly by increasing leg convective oxygen transport.

Hypertension is associated with blunted NO-mediated leg vasodilator responsiveness that is reversed by high-intensity training in postmenopausal women.

The menopausal transition is associated with increased prevalence of hypertension, and in time, postmenopausal women (PMW) will exhibit a cardiovascular disease risk score similar to male counterparts. Hypertension is associated with vascular dysfunction, but whether hypertensive (HYP) PMW have blunted nitric oxide (NO)-mediated leg vasodilator responsiveness and whether this is reversible by high-intensity training (HIT) is unknown. To address these questions, we examined the leg vascular conductance (LVC) in response to femoral infusion of acetylcholine (ACh) and sodium nitroprusside (SNP) and skeletal muscle markers of oxidative stress and NO bioavailability before and after HIT in PMW [12.9 ± 6.0 (means ± SD) years since last menstrual cycle]. We hypothesized that ACh- and SNP-induced LVC responsiveness was reduced in hypertensive compared with normotensive (NORM) PMW and that 10 wk of HIT would reverse the blunted LVC response and decrease blood pressure (BP). Nine hypertensive (HYP (clinical systolic/diastolic BP, 149 ± 11/91 ± 83 mmHg) and eight normotensive (NORM (122 ± 13/75 ± 8 mmHg) PMW completed 10 wk of biweekly small-sided floorball training (4-5 × 3-5 min interspersed by 1-3-min rest periods). Before training, the SNP-induced change in LVC was lower (P < 0.05) in HYP compared with in NORM. With training, the ACh- and SNP-induced change in LVC at maximal infusion rates, i.e., 100 and 6 µg·min-1·kg leg mass-1, respectively, improved (P < 0.05) in HYP only. Furthermore, training decreased (P < 0.05) clinical systolic/diastolic BP (-15 ± 11/-9 ± 7 mmHg) in HYP and systolic BP (-10 ± 9 mmHg) in NORM. Thus, the SNP-mediated LVC responsiveness was blunted in HYP PMW and reversed by a period of HIT that was associated with a marked decrease in clinical BP.

High-intensity exercise training enhances mitochondrial oxidative phosphorylation efficiency in a temperature-dependent manner in human skeletal muscle: implications for exercise performance.

The purpose of the present study was to investigate whether exercise training-induced adaptations in human skeletal muscle mitochondrial bioenergetics are magnified under thermal conditions resembling sustained intense contractile activity and whether training-induced changes in mitochondrial oxidative phosphorylation (OXPHOS) efficiency influence exercise efficiency. Twenty healthy men performed 6 wk of high-intensity exercise training [i.e., speed endurance training (SET; n = 10)], or maintained their usual lifestyle (n = 10). Before and after the intervention, mitochondrial respiratory function was determined ex vivo in permeabilized muscle fibers under experimentally-induced normothermia (35°C) and hyperthermia (40°C) mimicking in vivo muscle temperature at rest and during intense exercise, respectively. In addition, activity and content of muscle mitochondrial enzymes and proteins were quantified. Exercising muscle efficiency was determined in vivo by measurements of leg hemodynamics and blood parameters during one-legged knee-extensor exercise. SET enhanced maximal OXPHOS capacity and OXPHOS efficiency at 40°C, but not at 35°C, and attenuated hyperthermia-induced decline in OXPHOS efficiency. Furthermore, SET increased expression of markers of mitochondrial content and up-regulated content of MFN2, DRP1, and ANT1. Also, SET improved exercise efficiency and capacity. These findings indicate that muscle mitochondrial bioenergetics adapts to high-intensity exercise training in a temperature-dependent manner and that enhancements in mitochondrial OXPHOS efficiency may contribute to improving exercise performance.-Fiorenza, M., Lemminger, A. K., Marker, M., Eibye, K., Iaia, F. M., Bangsbo, J., Hostrup, M. High-intensity exercise training enhances mitochondrial oxidative phosphorylation efficiency in a temperature-dependent manner in human skeletal muscle: implications for exercise performance.

Efficacy of 10-20-30 training versus moderate-intensity continuous training on HbA1c, body composition and maximum oxygen uptake in male patients with type 2 diabetes: A randomized controlled trial.

AIM: To compare the efficacy of 10-20-30 training versus moderate-intensity continuous training (MICT) on HbA1c, body composition and maximum oxygen uptake (V˙O2 max) in male patients with type 2 diabetes (T2D). MATERIALS AND METHODS: Fifty-one male participants with T2D were randomly assigned (1:1) to a 10-20-30 (N = 26) and a MICT (N = 25) training group. Interventions consisted of supervised cycling three times weekly for 10 weeks, lasting 29 minutes (10-20-30) and 50 minutes (MICT) in a local non-clinical setting. The primary outcome was change in HbA1c from baseline to 10-week follow-up. RESULTS: Of 51 participants enrolled, 44 (mean age 61.0 ± 6.8 [mean ± SD] years, diagnosed 7.5 ± 5.8 years, baseline HbA1c 7.4% ± 1.3%) were included in the analysis. Training compliance was 84% and 86% in 10-20-30 and MICT, respectively. No adverse events occurred during the intervention. HbA1c decreased (P <0.001) by 0.5 (95% CI -0.72 to -0.21) percentage points with training in 10-20-30, with no change in MICT. The change in 10-20-30 was greater (P <0.05) than in MICT. Visceral fat mass decreased (P <0.05) only with 10-20-30 training, whereas total fat mass decreased (P <0.01) and V˙O2 max increased (P <0.01) with training in both groups. CONCLUSIONS: Ten weeks of 10-20-30 training was superior to MICT in lowering HbA1c, and only 10-20-30 training decreased visceral fat mass in patients with T2D. Furthermore, 10-20-30 training was as effective as MICT in reducing total fat mass and increasing V˙O2 max, despite a 42% lower training time commitment.

Cycling with blood flow restriction improves performance and muscle K+ regulation and alters the effect of anti-oxidant infusion in humans.

KEY POINTS: Training with blood flow restriction (BFR) is a well-recognized strategy for promoting muscle hypertrophy and strength. However, its potential to enhance muscle function during sustained, intense exercise remains largely unexplored. In the present study, we report that interval training with BFR augments improvements in performance and reduces net K+ release from contracting muscles during high-intensity exercise in active men. A better K+ regulation after BFR-training is associated with an elevated blood flow to exercising muscles and altered muscle anti-oxidant function, as indicated by a higher reduced to oxidized glutathione (GSH:GSSG) ratio, compared to control, as well as an increased thigh net K+ release during intense exercise with concomitant anti-oxidant infusion. Training with BFR also invoked fibre type-specific adaptations in the abundance of Na+ ,K+ -ATPase isoforms (α1 , ß1 , phospholemman/FXYD1). Thus, BFR-training enhances performance and K+ regulation during intense exercise, which may be a result of adaptations in anti-oxidant function, blood flow and Na+ ,K+ -ATPase-isoform abundance at the fibre-type level. ABSTRACT: We examined whether blood flow restriction (BFR) augments training-induced improvements in K+ regulation and performance during intense exercise in men, and also whether these adaptations are associated with an altered muscle anti-oxidant function, blood flow and/or with fibre type-dependent changes in Na+ ,K+ -ATPase-isoform abundance. Ten recreationally-active men (25 ± 4 years, 49.7 ± 5.3 mL kg-1  min-1 ) performed 6 weeks of interval cycling, where one leg trained without BFR (control; CON-leg) and the other trained with BFR (BFR-leg, pressure: ∼180 mmHg). Before and after training, femoral arterial and venous K+ concentrations and artery blood flow were measured during single-leg knee-extensor exercise at 25% (Ex1) and 90% of thigh incremental peak power (Ex2) with i.v. infusion of N-acetylcysteine (NAC) or placebo (saline) and a resting muscle biopsy was collected. After training, performance increased more in BFR-leg (23%) than in CON-leg (12%, P < 0.05), whereas K+ release during Ex2 was attenuated only from BFR-leg (P < 0.05). The muscle GSH:GSSG ratio at rest and blood flow during exercise was higher in BFR-leg than in CON-leg after training (P < 0.05). After training, NAC increased resting muscle GSH concentration and thigh net K+ release during Ex2 only in BFR-leg (P < 0.05), whereas the abundance of Na+ ,K+ -ATPase-isoform α1 in type II (51%), ß1 in type I (33%), and FXYD1 in type I (108%) and type II (60%) fibres was higher in BFR-leg than in CON-leg (P < 0.05). Thus, training with BFR elicited greater improvements in performance and reduced thigh K+ release during intense exercise, which were associated with adaptations in muscle anti-oxidant function, blood flow and Na+ ,K+ -ATPase-isoform abundance at the fibre-type level.

Effect of beta2 -adrenergic agonist and resistance training on maximal oxygen uptake and muscle oxidative enzymes in men.

While beta2 -adrenoceptor stimulation has been shown to increase lean mass and to alter metabolic properties of skeletal muscle, adaptations in muscle oxidative enzymes and maximal oxygen uptake ( V ˙ O2max ) in response to beta2 -adrenergic agonist treatment are inadequately explored in humans, particularly in association with resistance training. Herein, we investigated beta2 -adrenergic-induced changes in V ˙ O2max , leg and arm composition, and muscle content of oxidative enzymes in response to treatment with the selective beta2 -adrenergic agonist terbutaline with and without concurrent resistance training in young men. Forty-six subjects were randomized to 4 weeks of lifestyle maintenance (n = 23) or resistance training (n = 23). Within the lifestyle maintenance and resistance training group, subjects received daily terbutaline (8 × 0.5 mg) (n = 13) or placebo (n = 10) treatment. No apparent treatment by training interactions was observed during the study period. Terbutaline increased leg and arm lean mass with the intervention, whereas no treatment differences were observed in absolute V ˙ O2max and incremental peak power output (iPPO). Treatment main effects were observed for V ˙ O2 -reserve (P < .05), V ˙ O2max relative to body mass (P < .05), V ˙ O2max relative to leg lean mass (P < .01), and iPPO relative to leg lean mass, in which terbutaline had a negative effect compared with placebo. Furthermore, content of electron transport chain complex I-V decreased by 11% (P < .05) for terbutaline compared with placebo. Accordingly, chronic treatment with the selective beta2 -adrenergic agonist terbutaline may negatively affect V ˙ O2max and iPPO in relative terms, but not in absolute.

In-season adaptations to intense intermittent training and sprint interval training in sub-elite football players.

This study investigated the in-season effect of intensified training comparing the efficacy of duration-matched intense intermittent exercise training with sprint interval training in increasing intermittent running performance, sprint ability, and muscle content of proteins related to ion handling and metabolism in football players. After the first two weeks in the season, 22 sub-elite football players completed either 10 weeks of intense intermittent training using the 10-20-30 training concept (10-20-30, n = 12) or sprint interval training (SIT, n = 10; work/rest ratio: 6-s/54-s) three times weekly, with a ~20% reduction in weekly training time. Before and after the intervention, players performed a Yo-Yo intermittent recovery test level 1 (Yo-Yo IR1) and a 30-m sprint test. Furthermore, players had a muscle biopsy taken from the vastus lateralis. Yo-Yo IR1 performance increased by 330 m (95%CI: 178-482, P ≤ 0.01) in 10-20-30, whereas no change was observed in SIT. Sprint time did not change in 10-20-30 but decreased by 0.04 second (95%CI: 0.00-0.09, P ≤ 0.05) in SIT. Muscle content of HADHA (24%, P ≤ 0.01), PDH-E1α (40%, P ≤ 0.01), complex I-V of the electron transport chain (ETC) (51%, P ≤ 0.01) and Na+ , K+ -ATPase subunits α2 (33%, P ≤ 0.05) and ß1 (27%, P ≤ 0.05) increased in 10-20-30, whereas content of DHPR (27%, P ≤ 0.01) and complex I-V of the ETC (31%, P ≤ 0.05) increased in SIT. Intense intermittent training, combining short sprints and a high aerobic load, is superior to regular sprint interval training in increasing intense intermittent running performance during a Yo-Yo IR1 test and muscle content of PDH-E1α and HADHA in sub-elite football players.

N-Acetyl cysteine does not improve repeated intense endurance cycling performance of well-trained cyclists.

PURPOSE: To evaluate the effect of antioxidant supplementation on intense endurance exercise performance and the physiologic exercise response acutely and in early recovery. METHODS: Well-trained cyclists (n = 11, peak VO2: 69 ± 7 ml/min/kg) completed two identical standardized 20-min warm-up periods (WU-1 and WU-2) prior to two performance tests (PT) with a duration of ~ 4 min representing a qualifying (PT-1) and final race (PT-2) on the same day separated by 90 min. Subjects were supplemented orally with placebo (PLA) and N-acetyl cysteine (NAC; 20 mg/kg) before exercise in a double-blinded crossover design. RESULTS: Mean power during PT-1 did not differ (P = 0.39) between PLA (400 ± 44 W) and NAC (401 ± 44 W) as was the case during PT-2 with similar performance (P = 0.74) between PLA (401 ± 43 W) and NAC (400 ± 42 W). Subjective "readiness" was lowered by prior exhaustive exercise from PT-1 to PT-2 (P = 0.012) in both PLA and NAC. Plasma total antioxidant capacity was not affected by supplementation and prior exhaustive exercise (respective main effects: P = 0.83 and P = 0.19) which also was observed for peak VO2 at ~ 5 L/min (P = 0.84 and P = 0.30). In WU-1 and WU-2, both cycling economy at ~ 20% (P = 0.10 and P = 0.21) and plasma potassium at ~ 5 mmol/L (P = 0.46 and P = 0.26) were unaffected by supplementation and prior exercise. CONCLUSIONS: Athletes executing maximal efforts of a ~ 4-min duration twice daily, as seen in track cycling, appear to gain no benefit from oral NAC supplementation on acute and subsequent performance following short-term recovery. Moreover, well-trained cyclists exhibit rapid recovery from a single bout of intense endurance cycling.

Copenhagen Consensus statement 2019: physical activity and ageing.

From 19th to 22nd November 2018, 26 researchers representing nine countries and a variety of academic disciplines met in Snekkersten, Denmark, to reach evidence-based consensus about physical activity and older adults. It was recognised that the term 'older adults' represents a highly heterogeneous population. It encompasses those that remain highly active and healthy throughout the life-course with a high intrinsic capacity to the very old and frail with low intrinsic capacity. The consensus is drawn from a wide range of research methodologies within epidemiology, medicine, physiology, neuroscience, psychology and sociology, recognising the strength and limitations of each of the methods. Much of the evidence presented in the statements is based on longitudinal associations from observational and randomised controlled intervention studies, as well as quantitative and qualitative social studies in relatively healthy community-dwelling older adults. Nevertheless, we also considered research with frail older adults and those with age-associated neurodegenerative diseases, such as Alzheimer's and Parkinson's disease, and in a few cases molecular and cellular outcome measures from animal studies. The consensus statements distinguish between physical activity and exercise. Physical activity is used as an umbrella term that includes both structured and unstructured forms of leisure, transport, domestic and work-related activities. Physical activity entails body movement that increases energy expenditure relative to rest, and is often characterised in terms of intensity from light, to moderate to vigorous. Exercise is defined as a subset of structured physical activities that are more specifically designed to improve cardiorespiratory fitness, cognitive function, flexibility balance, strength and/or power. This statement presents the consensus on the effects of physical activity on older adults' fitness, health, cognitive functioning, functional capacity, engagement, motivation, psychological well-being and social inclusion. It also covers the consensus on physical activity implementation strategies. While it is recognised that adverse events can occur during exercise, the risk can be minimised by carefully choosing the type of activity undertaken and by consultation with the individual's physician when warranted, for example, when the individual is frail, has a number of co-morbidities, or has exercise-related symptoms, such as chest pain, heart arrhythmia or dizziness. The consensus was obtained through an iterative process that began with the presentation of the state-of-the-science in each domain, followed by group and plenary discussions. Ultimately, the participants reached agreement on the 30-item consensus statements.