Hypoxia mediated release of endothelial microparticles and increased association of S100A12 with circulating neutrophils

Microparticles are released from the endothelium under normal homeostatic conditions and have been shown elevated in disease states, most notably those characterised by endothelial dysfunction. The endothelium is sensitive to oxidative stress/status and vascular cell adhesion molecule-1 (VCAM-1) expression is upregulated upon activated endothelium, furthermore the presence of VCAM-1 on microparticles is known. S100A12, a calcium binding protein part of the S100 family, is shown to be present on circulating leukocytes and is thought a sensitive marker to local inflammatory process, which may be driven by oxidative stress. Eight healthy males were subjected to breathing hypoxic air (15% O2, approximately equivalent to 3000 metres altitude) for 80 minutes in a temperature controlled laboratory and venous blood samples were processed immediately for VCAM-1 microparticles (VCAM-1 MP) and S100A12 association with leukocytes by flow cytometry. A pre-hypoxic blood sample was used for comparison. Both VCAM-1 MP and S100A12 association with neutrophils were significantly elevated post hypoxic breathing later declining to levels observed in the pre-test samples. A similar trend was observed in both cases and a correlation may exist between these two markers in response to hypoxia. These data offer evidence using novel markers of endothelial and circulating blood responses to hypoxia

Reproducibility of creatine kinase: how useful is this measurement tool?

Establishing the reproducibility of a measurement is essential for repeated testing to ensure that any systematic change is a result of an external influence (i.e. intervention), as oppossed to normal random variation. Although some degree of error is inherent in any measure, a measurement tool should yield consistent results that do not fluctuate to an unacceptable degree from one test to another. Creatine kinase (CK) is consistently measured in the blood as a marker of exercise induced muscle damage (EIMD). However, its usefulness as a predictive tool to examine the temporal pattern, and magnitude of muscle damage has been questioned. PURPOSE:The main aim of the present study was to employ a variety of reproducibility statistics in order to examine the typical level of measurement error for CK. METHODS: Fifty (36 male, 14 female), apparently healthy participants completed three trials on three separate occasions with each trial separated by 48 - 72 h. The initial trial served as a familiarisation. During trials 2 and 3 (48 h), CK measures were obtained using standard fingerprick technique, and analysed in duplicate immediatley using a colorimetric assay procedure. Each participant completed their trials at the same time of day, following identical pre-test procedures. RESULTS: The intra-test coefficient of variation (CV) within our laboratory was 9%. Dependent t-tests indicated there was no systematic bias between trials (p = 0.82). The interdian CV displayed low reproducibility (20%). Furthermore, the 95% limits of agreement (LoA) were -69.7 to 63.5 iµ/L. However, the intraclass correlation coefficient (ICC) was 0.90, which can be clasified as displaying ‘high’ reproducibility. CONCLUSION: The interdian CV demonstrates that under identical resting conditions (48 h apart), CK displays inherent low absoulte reproducibility, which may obscure a true experimental effect. However, interpretation of the ICC, suggests that CK has high relative reproducibility. The high range of observed CK values is thought to have increased the size of the correlation. Subsequently, an indivdual change in CK following EIMD may not be indicative of the magnitude of damage, and may simply be a result of the inherent variation (e.g. biological). Therefore, it is advised that caution should be taken when using CK within experimental research, and as an indication of when an athlete has recovered, and is able to recommence training

The cytokine response to a 30 min downhill run

ISEI Abstract – 7 The cytokine response to a 30 min downhill run L TAYLOR1, CHRISMAS BCR1, CARROLL S2, SMITH A3, PEMBERTON P3, SIEGLER JC4 and MIDGLEY AW5. 1 Applied Sport and Exercise Physiology (ASEP) & Muscle Cellular and Molecular Physiology (MCMP) research groups, Institute of Sport and Physical Activity Research (ISPAR), Department of Sport & Exercise Sciences, University of Bedfordshire, Bedford, UK. 2Department of Sport, Health & Exercise Science, The University of Hull, Hull, UK. 3Department of Clinical Biochemistry, Central Manchester Foundation Trust, Manchester, UK. 4School of Science & Health, University of Western Sydney, Sydney, Australia. 5Department of Sport & Physical Activity, Edge Hill University, Ormskirk, UK. ABSTRACT Eccentric exercise has been ubiquitously shown to result in exericse induced muscle damage (EIMD), accompanied with delayed onset muscle soreness (DOMS). Although eccentric exercise may induce greater neuromuscular adaptation, functional performance may be impaired, and soreness may persist for several days following this type of exercise. This is primarily thought to be due to structural damage to the muscle fibres. In addition to the mechanical theory of EIMD, it has been suggested that an increased inflammatory response may be associated with DOMS. Furthermore, it is possible that the inflammatory response may play a role in mediating recovery, and adaptation following EIMD. However, the effects of EIMD on markers of inflammation have produced inconsistent results. PURPOSE: The main aim of the present study was to investigate the cytokine response to a 30 min downhill run. METHODS: Fifty (36 male, 14 female), apparently healthy participants performed a 30 min downhill run (-12.5%, 70% Vmax). Interleukin 6 (IL-6), high sensitivity C reactive protein (hs-CRP), and tumor necrosis factor alpha (TNF-α) were measured at 1 h, 24 h and 48 h post downhill run. Additionally, isometric maximum voluntary contraction (MVC), and perceived muscle soreness were measured at 24 h and 48 h post downhill run. RESULTS: Detectable levles of TNF-α were only present in three participants, and therefore, these data were excluded from the analysis. There was no significant difference in IL-6 or hs-CRP at any time point (p \u3e 0.10). However, there was a significant decrease in MVC (p ≤ 0.001). On average MVC decreased by 11% and 8% in the dominant and non-dominant leg at 24 h and 48 h respectively. Furthermore, there was a significant increase in muscle soreness (p \u3c 0.001). On average soreness increased by 49 mm and 51 mm 24 h and 48 h post downhill run. CONCLUSION: The significant increase in muscle soreness in the present study is indicative of EIMD. Furthermore, the significant decrement in MVC at 24 h and 48 h post downhill run, demonstrates that neuromuscular function was impaired. The lack of any significant increase in the cytokine response, supports the theory that mechanical damage is the primary mechanism associated with the EIMD and DOMS phenomenon. Nevertheless, when interpreting these results it is important to consider that due to the sampling times employed in the present study, an inflammatory response may have been missed

Is a verification phase useful for confirming maximal oxygen uptake in apparently healthy adults? A systematic review and meta-analysis

BackgroundThe 'verification phase' has emerged as a supplementary procedure to traditional maximal oxygen uptake (VO2max) criteria to confirm that the highest possible VO2 has been attained during a cardiopulmonary exercise test (CPET).ObjectiveTo compare the highest VO2 responses observed in different verification phase procedures with their preceding CPET for confirmation that VO2max was likely attained.MethodsMEDLINE (accessed through PubMed), Web of Science, SPORTDiscus, and Cochrane (accessed through Wiley) were searched for relevant studies that involved apparently healthy adults, VO2max determination by indirect calorimetry, and a CPET on a cycle ergometer or treadmill that incorporated an appended verification phase. RevMan 5.3 software was used to analyze the pooled effect of the CPET and verification phase on the highest mean VO2. Meta-analysis effect size calculations incorporated random-effects assumptions due to the diversity of experimental protocols employed. I2 was calculated to determine the heterogeneity of VO2 responses, and a funnel plot was used to check the risk of bias, within the mean VO2 responses from the primary studies. Subgroup analyses were used to test the moderator effects of sex, cardiorespiratory fitness, exercise modality, CPET protocol, and verification phase protocol.ResultsEighty studies were included in the systematic review (total sample of 1,680 participants; 473 women; age 19-68 yr.; VO2max 3.3 ± 1.4 L/min or 46.9 ± 12.1 mL·kg-1·min-1). The highest mean VO2 values attained in the CPET and verification phase were similar in the 54 studies that were meta-analyzed (mean difference = 0.03 [95% CI = -0.01 to 0.06] L/min, P = 0.15). Furthermore, the difference between the CPET and verification phase was not affected by any of the potential moderators such as verification phase intensity (P = 0.11), type of recovery utilized (P = 0.36), VO2max verification criterion adoption (P = 0.29), same or alternate day verification procedure (P = 0.21), verification-phase duration (P = 0.35), or even according to sex, cardiorespiratory fitness level, exercise modality, and CPET protocol (P = 0.18 to P = 0.71). The funnel plot indicated that there was no significant publication bias.ConclusionsThe verification phase seems a robust procedure to confirm that the highest possible VO2 has been attained during a ramp or continuous step-incremented CPET. However, given the high concordance between the highest mean VO2 achieved in the CPET and verification phase, findings from the current study would question its necessity in all testing circumstances.Prospero registration idCRD42019123540

Acute effects of mixed circuit training on hemodynamic and cardiac autonomic control in chronic hemiparetic stroke patients: a randomized controlled crossover trial

Objectives: To investigate whether a single bout of mixed circuit training (MCT) can elicit acute blood pressure (BP) reduction in chronic hemiparetic stroke patients, a phenomenon also known as post-exercise hypotension (PEH). Methods: Seven participants (58 ± 12 years) performed a non-exercise control session (CTL) and a single bout of MCT on separate days and in a randomized counterbalanced order. The MCT included 10 exercises with 3 sets of 15-repetition maximum per exercise, with each set interspersed with 45 s of walking. Systolic (SBP) and diastolic (DBP) blood pressure, mean arterial pressure (MAP), cardiac output (Q), systemic vascular resistance (SVR), baroreflex sensitivity (BRS), and heart rate variability (HRV) were assessed 10 min before and 40 min after CTL and MCT. BP and HRV were also measured during an ambulatory 24-h recovery period. Results: Compared to CTL, SBP (∆-22%), DBP (∆-28%), SVR (∆-43%), BRS (∆-63%), and parasympathetic activity (HF; high-frequency component: ∆-63%) were reduced during 40 min post-MCT (p < 0.05), while Q (∆35%), sympathetic activity (LF; low-frequency component: ∆139%) and sympathovagal balance (LF:HF ratio: ∆145%) were higher (p < 0.001). In the first 10 h of ambulatory assessment, SBP (∆-7%), MAP (∆-6%), and HF (∆-26%) remained lowered, and LF (∆11%) and LF:HF ratio (∆13%) remained elevated post-MCT vs. CTL (p < 0.05). Conclusion: A single bout of MCT elicited prolonged PEH in chronic hemiparetic stroke patients. This occurred concurrently with increased sympathovagal balance and lowered SVR, suggesting vasodilation capacity is a major determinant of PEH in these patients. This clinical trial was registered in the Brazilian Clinical Trials Registry (RBR-5dn5zd), available at https://ensaiosclinicos.gov.br/rg/RBR-5dn5zd. Clinical Trial Registration: https://ensaiosclinicos.gov.br/rg/RBR-5dn5zd, identifier RBR-5dn5z

Evaluation of true maximal oxygen uptake based on a novel set of standardized criteria

In this study, criteria are used to identify whether a subject has elicited maximal oxygen uptake. We evaluated the validity of traditional maximal oxygen uptake criteria and propose a novel set of criteria. Twenty athletes completed a maximal oxygen uptake test, consisting of an incremental phase and a subsequent supramaximal phase to exhaustion (verification phase). Traditional and novel maximal oxygen uptake criteria were evaluated. Novel criteria were: oxygen uptake plateau defined as the difference between modelled and actual maximal oxygen uptake >50% of the regression slope of the individual oxygen uptake-workrate relationship; as in the first criterion, but for maximal verification oxygen uptake; and a difference of [less than or equal to]4 beats x [min.sup.-1] between maximal heart rate values in the 2 phases. Satisfying the traditional oxygen uptake plateau criterion was largely an artefact of the between-subject variation in the oxygen uptake-workrate relationship. Secondary criteria, supposedly an indicator of maximal effort, were often satisfied long before volitional exhaustion, even at intensities as low as 61% maximal oxygen uptake. No significant mean differences were observed between the incremental and verification phases for oxygen uptake (t = 0.4; p = 0.7) or heart rate (t = 0.8; p = 0.5). The novel oxygen uptake plateau criterion, maximal oxygen uptake verification criterion, and maximal heart rate verification criterion were satisfied by 17, 18, and 18 subjects, respectively. The small individual absolute differences in oxygen uptake between incremental and verification phases observed in most subjects provided additional confidence that maximal oxygen uptake was elicited. Current maximal oxygen uptake criteria were not valid and novel criteria should be further explored

Exercise tolerance during VO2max testing is a multifactorial psychobiological phenomenon

Fifty-nine men completed a VO2max test and a questionnaire to establish reasons for test termination, perceived exercise reserve (difference between actual test duration and the duration the individual perceived could have been achieved if continued until physical limitation), and perception of verbal encouragement. Participants gave between 1 and 11 factors as reasons for test termination, including leg fatigue, various perceptions of physical discomfort, safety concerns, and achievement of spontaneously set goals. The two most common main reasons were leg fatigue and breathing discomfort, which were predicted by pre-to-post test changes in pulmonary function (p = 0.038) and explosive leg strength (p = 0.042; R2 = 0.40). Median (interquartile range) perceived exercise reserve, was 45 (50) s. Two-thirds of participants viewed verbal encouragement positively, whereas one-third had a neutral or negative perception. This study highlights the complexity of exercise tolerance during VO2max testing and more research should explore these novel findings

The Effect of Antioxidant Supplementation on Fatigue during Exercise: Potential Role for NAD+(H)

This study compared serum pyridine levels (NAD+ /NADH) in trained (n = 6) and untrained (n = 7) subjects after continuous progressive exercise at 50%, 70% then 95% of physical work capacity until fatigue (TTF) after consuming a placebo or antioxidant (AO) cocktail (Lactaway©). An increase of 17% in TTF was observed in AO as compared to placebo (p = 0.032). This was accompanied by a significant increase in serum NAD+ levels (p = 0.037) in the AO supplemented group post exercise. The increases in NAD+ and improved endurance reflect lower oxidative stress-induced suppression of aerobic respiration