Age-Dependent Decline in Common Femoral Artery Flow-Mediated Dilation and Wall Shear Stress in Healthy Subjects.

Femoral artery (FA) endothelial function is a promising biomarker of lower extremity vascular health for peripheral artery disease (PAD) prevention and treatment; however, the impact of age on FA endothelial function has not been reported in healthy adults. Therefore, we evaluated the reproducibility and acceptability of flow-mediated dilation (FMD) in the FA and brachial artery (BA) (n = 20) and performed cross-sectional FA- and BA-FMD measurements in healthy non-smokers aged 22−76 years (n = 50). FMD protocols demonstrated similar good reproducibility. Leg occlusion was deemed more uncomfortable than arm occlusion; thigh occlusion was less tolerated than forearm and calf occlusion. FA-FMD with calf occlusion was lower than BA-FMD (6.0 ± 1.1% vs 6.4 ± 1.3%, p = 0.030). Multivariate linear regression analysis indicated that age (−0.4%/decade) was a significant independent predictor of FA-FMD (R2 = 0.35, p = 0.002). The age-dependent decline in FMD did not significantly differ between FA and BA (pinteraction agexlocation = 0.388). In older participants, 40% of baseline FA wall shear stress (WSS) values were <5 dyne/cm2, which is regarded as pro-atherogenic. In conclusion, endothelial function declines similarly with age in the FA and the BA in healthy adults. The age-dependent FA enlargement results in a critical decrease in WSS that may explain part of the age-dependent predisposition for PAD.

Safety and Feasibility Assessment of Repetitive Vascular Occlusion Stimulus (RVOS) Application to Multi-Organ Failure Critically Ill Patients: A Pilot Randomised Controlled Trial.

Muscle wasting is implicated in the pathogenesis of intensive care unit acquired weakness (ICU-AW), affecting 40% of patients and causing long-term physical disability. A repetitive vascular occlusion stimulus (RVOS) limits muscle atrophy in healthy and orthopaedic subjects, thus, we explored its application to ICU patients. Adult multi-organ failure patients received standard care +/- twice daily RVOS {4 cycles of 5 min tourniquet inflation to 50 mmHg supra-systolic blood pressure, and 5 min complete deflation} for 10 days. Serious adverse events (SAEs), tolerability, feasibility, acceptability, and exploratory outcomes of the rectus femoris cross-sectional area (RFCSA), echogenicity, clinical outcomes, and blood biomarkers were assessed. Only 12 of the intended 32 participants were recruited. RVOS sessions (76.1%) were delivered to five participants and two could not tolerate it. No SAEs occurred; 75% of participants and 82% of clinical staff strongly agreed or agreed that RVOS is an acceptable treatment. RFCSA fell significantly and echogenicity increased in controls (n = 5) and intervention subjects (n = 4). The intervention group was associated with less frequent acute kidney injury (AKI), a greater decrease in the total sequential organ failure assessment score (SOFA) score, and increased insulin-like growth factor-1 (IGF-1), and reduced syndecan-1, interleukin-4 (IL-4) and Tumor necrosis factor receptor type II (TNF-RII) levels. RVOS application appears safe and acceptable, but protocol modifications are required to improve tolerability and recruitment. There were signals of possible clinical benefit relating to RVOS application.

Consumption of New Zealand Blackcurrant Extract Improves Recovery from Exercise-Induced Muscle Damage in Non-Resistance Trained Men and Women: A Double-Blind Randomised Trial.

BACKGROUND: Blackcurrant is rich in anthocyanins that may protect against exercise-induced muscle damage (EIMD) and facilitate a faster recovery of muscle function. We examined the effects of New Zealand blackcurrant (NZBC) extract on indices of muscle damage and recovery following a bout of strenuous isokinetic resistance exercise. METHODS: Using a double-blind, randomised, placebo controlled, parallel design, twenty-seven healthy participants received either a 3 g·day-1 NZBC extract (n = 14) or the placebo (PLA) (n = 13) for 8 days prior to and 4 days following 60 strenuous concentric and eccentric contractions of the biceps brachii muscle on an isokinetic dynamometer. Muscle soreness (using a visual analogue scale), maximal voluntary contraction (MVC), range of motion (ROM) and blood creatine kinase (CK) were assessed before (0 h) and after (24, 48, 72 and 96 h) exercise. RESULTS: Consumption of NZBC extract resulted in faster recovery of baseline MVC (p = 0.04), attenuated muscle soreness at 24 h (NZBC: 21 ± 10 mm vs. PLA: 40 ± 23 mm, p = 0.02) and 48 h (NZBC: 22 ± 17 vs. PLA: 44 ± 26 mm, p = 0.03) and serum CK concentration at 96 h (NZBC: 635 ± 921 UL vs. PLA: 4021 ± 4319 UL, p = 0.04) following EIMD. CONCLUSIONS: Consumption of NZBC extract prior to and following a bout of eccentric exercise attenuates muscle damage and improves functional recovery. These findings are of practical importance in recreationally active and potentially athletic populations, who may benefit from accelerated recovery following EIMD.

The relationship between vitamin D status, intake and exercise performance in UK University-level athletes and healthy inactive controls.

The potential ergogenic effects of vitamin D (vitD) in high performing athletes has received considerable attention in the literature and media. However, little is known about non-supplemented university athletes and students residing at a higher latitude. This study aimed to investigate the effects of vitD (biochemical status and dietary intake) on exercise performance in UK university athletes and sedentary students. A total of 34 athletes and 16 sedentary controls were studied during the spring and summer months. Serum vitD status and sunlight exposure were assessed using LC-MS/MS and dosimetry, respectively. Muscular strength of the upper and lower body was assessed using handgrip and knee extensor dynamometry (KE). Countermovement jump (CMJ) and aerobic fitness were measured using an Optojump and VO2max test, respectively. Statistical analysis was performed using paired/ independent t-tests, ANCOVA and Pearson/ Spearman correlations, depending on normality. VitD status increased significantly over the seasons, with athletes measuring higher status both in spring (51.7±20.5 vs. 37.2±18.9 nmol/L, p = 0.03) and summer (66.7±15.8 vs 55.6±18.8 nmol/L, p = 0.04) when compared to controls, respectively. Notably, 22% of the subjects recruited were vitD deficient during the spring term only (<25nmol/L, n 9). Subjects with 'insufficient' vitD status (<50nmol/L) elicited significantly lower CMJ when contrasted to the vitD 'sufficient' (>50nmol/l) group (p = 0.055) and a lower VO2 max (p = 0.05) in the spring and summer term (p = 0.05 and p = 0.01, respectively). However, an ANCOVA test showed no significant difference detected for either CMJ or VO2max following adjustments for co-variates. In conclusion, we provide novel information on the vitD status, dietary intake, physical fitness and sunlight exposure of UK young adults across two separate seasons, for which there is limited data at present.

Seasonal variation in vitamin D status, bone health and athletic performance in competitive university student athletes: a longitudinal study.

Vitamin D deficiency has been commonly reported in elite athletes, but the vitamin D status of UK university athletes in different training environments remains unknown. The present study aimed to determine any seasonal changes in vitamin D status among indoor and outdoor athletes, and whether there was any relationship between vitamin D status and indices of physical performance and bone health. A group of forty-seven university athletes (indoor n 22, outdoor n 25) were tested during autumn and spring for serum vitamin D status, bone health and physical performance parameters. Blood samples were analysed for serum 25-hydroxyvitamin D (s-25(OH)D) status. Peak isometric knee extensor torque using an isokinetic dynamometer and jump height was assessed using an Optojump. Aerobic capacity was estimated using the Yo-Yo intermittent recovery test. Peripheral quantitative computed tomography scans measured radial bone mineral density. Statistical analyses were performed using appropriate parametric/non-parametric testing depending on the normality of the data. s-25(OH)D significantly fell between autumn (52·8 (sd 22·0) nmol/l) and spring (31·0 (sd 16·5) nmol/l; P < 0·001). In spring, 34 % of participants were considered to be vitamin D deficient (<25 nmol/l) according to the revised 2016 UK guidelines. These data suggest that UK university athletes are at risk of vitamin D deficiency. Thus, further research is warranted to investigate the concomitant effects of low vitamin D status on health and performance outcomes in university athletes residing at northern latitudes.

Repetitive vascular occlusion stimulus (RVOS) versus standard care to prevent muscle wasting in critically ill patients (ROSProx):a study protocol for a pilot randomised controlled trial.

BACKGROUND: Forty per cent of critically ill patients are affected by intensive care unit-acquired weakness (ICU-AW), to which skeletal muscle wasting makes a substantial contribution. This can impair outcomes in hospital, and can cause long-term physical disability after hospital discharge. No effective mitigating strategies have yet been identified. Application of a repetitive vascular occlusion stimulus (RVOS) a limb pressure cuff inducing brief repeated cycles of ischaemia and reperfusion, can limit disuse muscle atrophy in both healthy controls and bed-bound patients recovering from knee surgery. We wish to determine whether RVOS might be effective in mitigating against muscle wasting in the ICU. Given that RVOS can also improve vascular function in healthy controls, we also wish to assess such effects in the critically ill. We here describe a pilot study to assess whether RVOS application is safe, tolerable, feasible and acceptable for ICU patients. METHODS: This is a randomised interventional feasibility trial. Thirty-two ventilated adult ICU patients with multiorgan failure will be recruited within 48 h of admission and randomised to either the intervention arm or the control arm. Intervention participants will receive RVOS twice daily (except only once on day 1) for up to 10 days or until ICU discharge. Serious adverse events and tolerability (pain score) will be recorded; feasibility of trial procedures will be assessed against pre-specified criteria and acceptability by semi-structured interview. Together with vascular function, muscle mass and quality will be assessed using ultrasound and measures of physical function at baseline, on days 6 and 11 of study enrolment, and at ICU and hospital discharge. Blood and urine biomarkers of muscle metabolism, vascular function, inflammation and DNA damage/repair mechanism will also be analysed. The Health questionnaire will be completed 3 months after hospital discharge. DISCUSSION: If this study demonstrates feasibility, the derived data will be used to inform the design (and sample size) of an appropriately-powered prospective trial to clarify whether RVOS can help preserve muscle mass/improve vascular function in critically ill patients. TRIAL REGISTRATION: ISRCTN Registry, ISRCTN44340629. Registered on 26 October 2017.

The acute angiogenic signalling response to low-load resistance exercise with blood flow restriction.

This study investigated protein kinase activation and gene expression of angiogenic factors in response to low-load resistance exercise with or without blood flow restriction (BFR). In a repeated measures cross-over design, six males performed four sets of bilateral knee extension exercise at 20% 1RM (reps per set = 30:15:15:continued to fatigue) with BFR (110 mmHg) and without (CON). Muscle biopsies were obtained from the vastus lateralis before, 2 and 4 h post-exercise. mRNA expression was determined using real-time RT-PCR. Protein phosphorylation/expression was determined using Western blot. p38MAPK phosphorylation was greater (p = 0.05) at 2 h following BFR (1.3 ± 0.8) compared to CON (0.4 ± 0.3). AMPK phosphorylation remained unchanged. PGC-1α mRNA expression increased at 2 h (5.9 ± 1.3 vs. 2.1 ± 0.8; p = 0.03) and 4 h (3.2 ± 0.8 vs. 1.5 ± 0.4; p = 0.03) following BFR exercise with no change in CON. PGC-1α protein expression did not change following either exercise. BFR exercise enhanced mRNA expression of vascular endothelial growth factor (VEGF) at 2 h (5.2 ± 2.8 vs 1.7 ± 1.1; p = .02) and 4 h (6.8 ± 4.9 vs. 2.5 ± 2.7; p = .01) compared to CON. mRNA expression of VEGF-R2 and hypoxia-inducible factor 1α increased following BFR exercise but only eNOS were enhanced relative to CON. Matrix metalloproteinase-9 mRNA expression was not altered in response to either exercise. Acute low-load resistance exercise with BFR provides a targeted angiogenic response potentially mediated through enhanced ischaemic and shear stress stimuli.

Exercise duration-matched interval and continuous sprint cycling induce similar increases in AMPK phosphorylation, PGC-1α and VEGF mRNA expression in trained individuals.

PURPOSE: The effects of low-volume interval and continuous 'all-out' cycling, matched for total exercise duration, on mitochondrial and angiogenic cell signalling was investigated in trained individuals. METHODS: In a repeated measures design, 8 trained males ([Formula: see text], 57 ± 7 ml kg(-1) min(-1)) performed two cycling exercise protocols; interval (INT, 4 × 30 s maximal sprints interspersed by 4 min passive recovery) or continuous (CON, 2 min continuous maximal sprint). Muscle biopsies were obtained before, immediately after and 3 h post-exercise. RESULTS: Total work was 53 % greater (P = 0.01) in INT compared to CON (71.2 ± 7.3 vs. 46.3 ± 2.7 kJ, respectively). Phosphorylation of AMPK(Thr172) increased by a similar magnitude (P = 0.347) immediately post INT and CON (1.6 ± 0.2 and 1.3 ± 0.3 fold, respectively; P = 0.011), before returning to resting values at 3 h post-exercise. mRNA expression of PGC-1α (7.1 ± 2.1 vs. 5.5 ± 1.8 fold; P = 0.007), VEGF (3.5 ± 1.2 vs. 4.3 ± 1.8 fold; P = 0.02) and HIF-1α (2.0 ± 0.5 vs. 1.5 ± 0.3 fold; P = 0.04) increased at 3 h post-exercise in response to INT and CON, respectively; the magnitude of which were not different between protocols. CONCLUSIONS: Despite differences in total work done, low-volume INT and CON 'all-out' cycling, matched for exercise duration, provides a similar stimulus for the induction of mitochondrial and angiogenic cell signalling pathways in trained skeletal muscle.

The influence of participant characteristics on the relationship between cuff pressure and level of blood flow restriction.

PURPOSE: Previous investigations to establish factors influencing the blood flow restriction (BFR) stimulus have determined cuff pressures required for complete arterial occlusion, which does not reflect the partial restriction prescribed for this training technique. This study aimed to establish characteristics that should be accounted for when prescribing cuff pressures required for partial BFR. METHODS: Fifty participants were subjected to incremental blood flow restriction of the upper and lower limbs by proximal pneumatic cuff inflation. Popliteal and brachial artery diameter, blood velocity and blood flow was assessed with Doppler ultrasound. Height, body mass, limb circumference, muscle-bone cross-sectional area, adipose thickness (AT) and arterial blood pressure were measured and used in different models of hierarchical linear regression to predict the pressure at which 60 % BFR (partial occlusion) occurred. RESULTS: Combined analysis revealed a difference in cuff pressures required to elicit 60 % BFR in the popliteal (111 ± 12 mmHg) and brachial arteries (101 ± 12 mmHg). MAP (r = 0.58) and AT (r = -0.45) were the largest independent determinants of lower and upper body partial occlusion pressures. However, greater variance was explained by upper and lower limb regression models composed of DBP and BMI (48 %), and arm AT and DBP (30 %), respectively. CONCLUSION: Limb circumference has limited impact on the cuff pressure required for partial blood flow restriction which is in contrast to its recognised relationship with complete arterial occlusion. The majority of the variance in partial occlusion pressure remains unexplained by the predictor variables assessed in the present study.

Brachial artery characteristics and micro-vascular filtration capacity in rock climbers.

Rock climbers perform repeated isometric forearm muscle contractions subjecting the vasculature to repeated ischaemia and distorted haemodynamic signals. This study investigated forearm vascular characteristics in rock climbers compared to healthy untrained controls. Eight climbers (CLIMB) (BMI; 22.3, s = 2.0 kg/m(2), isometric handgrip strength; 46, s = 8 kg) were compared against eight untrained controls (CON) (BMI; 23.8, s = 2.6 kg/m(2), isometric handgrip strength; 37, s = 9 kg). Brachial artery diameter and blood flow were measured, using Doppler ultrasound, at rest and following 5-mins ischaemia (peak diameter) and ischaemic exercise (maximal dilation) to calculate flow mediated dilation (FMD) and dilatory capacity (DC). Capillary filtration capacity was assessed using venous occlusion plethysmography. Resting (4.30, s = 0.26 vs. 3.79, s = 0.39 mm), peak (4.67, s = 0.31 vs. 4.12, s = 0.45 mm) and maximal (5.14, s = 0.42 vs. 4.35, s = 0.47 mm) diameters were greater (P < 0.05) in CLIMB than CON, respectively, despite no difference in FMD (9.2, s = 2.6 vs. 8.7, s = 2.9%). Peak reactive hyperaemic blood flow (1136, s = 504 vs. 651, s = 221 ml/min) and capillary filtration capacity (3.8, s = 0.9 vs. 5.2, s = 0.7 ml.min(-1).mmHg(-1).100 ml tissue(-1) × 10(-3)) were greater (P < 0.05) in CLIMB compared to CON, respectively. Rock climbers exhibit structural vascular adaptation compared to untrained control participants but have similar vascular function. This may contribute to the enhanced ability of climbers to perform repeated isometric contractions.

Time course of regional vascular adaptations to low load resistance training with blood flow restriction.

Distortion to hemodynamic and ischemic stimuli during blood flow restriction (BFR) exercise may influence regional vascular adaptation. We examined changes at the conduit, resistance, and capillary level in response to low load resistance exercise with BFR. Eleven males (22 ± 3 yr, 178 ± 4 cm, 78 ± 9 kg) completed 6 wk (3 days/wk) unilateral plantar flexion training with BFR at 30% 1 repetition maximum (1-RM). The contralateral leg acted as a nonexercised control (CON). Popliteal artery function [flow-mediated dilation, FMD%] and structure [maximal diameter] and resistance vessel structure [peak reactive hyperemia] were assessed using Doppler ultrasound before and at 2-wk intervals. Calf filtration capacity was assessed using venous occlusion plethysmography before and after training. BFR training elicited an early increase in peak reactive hyperemia (1,400 ± 278 vs. 1,716 ± 362 ml/min at 0 vs. 2 wk; t-test: P = 0.047), a transient improvement in popliteal FMD% (5.0 ± 2.1, 7.6 ± 2.9, 6.6 ± 2.1, 5.7 ± 1.6% at 0, 2, 4 and 6 wk, respectively; ANOVA: P = 0.002), and an increase in maximum diameter (6.06 ± 0.44 vs. 6.26 ± 0.39 mm at 0 vs. 6 wk; Bonferroni t-test: P = 0.048). Capillary filtration increased after 6 wk BFR training (P = 0.043). No changes in the CON leg were observed. Adaptation occurred at all levels of the vascular tree in response to low load resistance exercise with BFR. Enhanced peak reactive hyperemia and transient improvement in popliteal artery function occurred before changes in artery structural capacity.

Brachial artery modifications to blood flow-restricted handgrip training and detraining.

Low load resistance training with blood flow restriction (BFR) can increase muscle size and strength, but the implications on the conduit artery are uncertain. We examined the effects of low-load dynamic handgrip training with and without BFR, and detraining, on measures of brachial artery function and structure. Nine male participants (26 ± 4 yr, 178 ± 3 cm, 78 ± 10 kg) completed 4 wk (3 days/wk) of dynamic handgrip training at 40% 1 repetition maximum (1RM). In a counterbalanced manner, one forearm trained under BFR (occlusion cuff at 80 mmHg) and the other under nonrestricted (CON) conditions. Brachial artery function [flow-mediated dilation (FMD)] and structure (diameter) were assessed using Doppler ultrasound. Measurements were made before training (pretraining), after training (posttraining), and after 2-wk no training (detraining). Brachial artery diameter at rest, in response to 5-min ischemia (peak diameter), and ischemic exercise (maximal diameter) increased by 3.0%, 2.4%, and 3.1%, respectively, after BFR training but not after CON. FMD did not change at any time point in either arm. Vascular measures in the BFR arm returned to baseline after 2 wk detraining with no change after CON. The data demonstrate that dynamic low-load handgrip training with BFR induced transient adaptations to conduit artery structure but not function.