Mobile health biometrics to prescribe immediate remote physical activity for enhancing uptake to cardiac rehabilitation (MOTIVATE-CR+): protocol for a randomised controlled feasibility trial.

INTRODUCTION: Cardiac rehabilitation (CR) can reduce cardiovascular mortality and improve health-related quality of life. In the United Kingdom, patient uptake of CR remains low (52%), falling well short of the target in the 2019 National Health Service long-term plan (85%). Mobile health (mHealth) technologies, offering biometric data to patients and healthcare professionals, may bridge the gap between supervised exercise and physical activity advice, enabling patients to engage in regular long-term physically active lifestyles. This randomised controlled trial (RCT) will evaluate the feasibility of mHealth technology when incorporated into a structured home-based walking intervention, in people with recent myocardial infarction. METHODS AND ANALYSIS: This is a feasibility, assessor blinded, parallel group RCT. Participants will be allocated to either CR standard care (control group) or CR standard care+mHealth supported exercise counselling (mHealth intervention group). Feasibility outcomes will include the number of patients approached, screened and eligible; the percentage of patients who decline CR (including reasons for declining), agree to CR and consent to being part of the study; the percentage of patients who enrol in standard CR and reasons for drop out; and the percentage of participants who complete clinical, physical and psychosocial outcomes to identify a suitable primary outcome for a future definitive trial. ETHICS AND DISSEMINATION: The trial was approved in the UK by the Northwest-Greater Manchester East Research Ethics Committee (22/NW/0301) and is being conducted in accordance with the Declaration of Helsinki and Good Clinical Practice. Results will be published in peer-reviewed journals and presented at national and international scientific meetings. TRIAL REGISTRATION NUMBERS: NCT05774587.

Adherence to unsupervised exercise in sedentary individuals: A randomised feasibility trial of two mobile health interventions.

Introduction: Adherence to unsupervised exercise is poor, yet unsupervised exercise interventions are utilised in most healthcare settings. Thus, investigating novel ways to enhance adherence to unsupervised exercise is essential. This study aimed to examine the feasibility of two mobile health (mHealth) technology-supported exercise and physical activity (PA) interventions to increase adherence to unsupervised exercise. Methods: Eighty-six participants were randomised to online resources (n = 44, females n = 29) or MOTIVATE (n = 42, females n = 28). The online resources group had access to booklets and videos to assist in performing a progressive exercise programme. MOTIVATE participants received exercise counselling sessions supported via mHealth biometrics which allowed instant participant feedback on exercise intensity, and communication with an exercise specialist. Heart rate (HR) monitoring, survey-reported exercise behaviour and accelerometer-derived PA were used to quantify adherence. Remote measurement techniques were used to assess anthropometrics, blood pressure, HbA1c and lipid profiles. Results: HR-derived adherence rates were 22 ± 34% and 113 ± 68% in the online resources and MOTIVATE groups, respectively. Self-reported exercise behaviour demonstrated moderate (Cohen's d = 0.63, CI = 0.27 to 0.99) and large effects (Cohen's d = 0.88, CI = 0.49 to 1.26) in favour of online resources and MOTIVATE groups, respectively. When dropouts were included, 84% of remotely gathered data were available, with dropouts removed data availability was 94%. Conclusion: Data suggest both interventions have a positive impact on adherence to unsupervised exercise but MOTIVATE enables participants to meet recommended exercise guidelines. Nevertheless, to maximise adherence to unsupervised exercise, future appropriately powered trials should explore the effectiveness of the MOTIVATE intervention.

Recommendations from Diabetes UK's 2022 diabetes and physical activity workshop.

AIMS: To describe the process and outputs of a workshop convened to identify key priorities for future research in the area of diabetes and physical activity and provide recommendations to researchers and research funders on how best to address them. METHODS: A 1-day research workshop was conducted, bringing together researchers, people living with diabetes, healthcare professionals, and members of staff from Diabetes UK to identify and prioritise recommendations for future research into physical activity and diabetes. RESULTS: Workshop attendees prioritised four key themes for further research: (i) better understanding of the physiology of exercise in all groups of people: in particular, what patient metabolic characteristics influence or predict the physiological response to physical activity, and the potential role of physical activity in beta cell preservation; (ii) designing physical activity interventions for maximum impact; (iii) promoting sustained physical activity across the life course; (iv) designing physical activity studies for groups with multiple long-term conditions. CONCLUSIONS: This paper outlines recommendations to address the current gaps in knowledge related to diabetes and physical activity and calls on the research community to develop applications in these areas and funders to consider how to stimulate research in these areas.

Clinical Considerations and Practical Advice for People Living With Type 2 Diabetes Who Undertake Regular Exercise or Aim to Exercise Competitively.

This article provides practical tips for advising people with type 2 diabetes on how to engage in regular exercise safely and effectively. Its focus is on individuals who wish to exceed the minimum physical activity recommendation of 150 minutes/week of moderate-intensity exercise or even compete in their chosen sport. Health care professionals who work with such individuals must have a basic understanding of glucose metabolism during exercise, nutritional requirements, blood glucose management, medications, and sport-related considerations. This article reviews three key aspects of individualized care for physically active people with type 2 diabetes: 1) initial medical assessment and pre-exercise screenings, 2) glucose monitoring and nutritional considerations, and 3) the combined glycemic effects of exercise and medications.

Remote maintenance cardiac rehabilitation (MAINTAIN): A protocol for a randomised feasibility study.

Background: Long-term adherence to exercise is often poor for people with coronary heart disease (CHD) who have completed supervised, centre-based cardiac rehabilitation. The aim of this study is to assess the feasibility of a remotely prescribed, delivered and monitored cardiac rehabilitation intervention using a wearable device to support long-term adherence to exercise and physical activity during maintenance of cardiac rehabilitation. Methods: After completing cardiac rehabilitation, 30 participants with CHD, will be randomised (1:1) to an intervention (n = 15) or a usual care group (n = 15) in a 12-month feasibility randomised controlled trial (RCT). The intervention will comprise of an exercise consultation, personalised exercise prescription delivered via a wearable activity monitor using biometric feedback, regular monitoring via check-ins, and feedback text-messages for 6-months. Participants will be assessed at baseline (following completion of cardiac rehabilitation) and at three-, six-, and 12-months post-randomisation. The primary outcome will be feasibility, including assessment of eligibility, recruitment, adherence, and acceptability. Secondary outcomes will include exercise capacity, physical activity behaviours, cardiovascular disease risk and quality of life. Semi-structured interviews will be conducted at three-, six-, and 12-months post-randomisation (and with those who drop-out) to explore the acceptability of the study intervention and procedures. A questionnaire will be offered to those who decline participation. Discussion: The MAINTAIN study will evaluate the feasibility of conducting a future definitive multi-centre RCT testing a remotely prescribed and monitored long-term mHealth maintenance exercise programme, versus usual care, for people with CHD who have completed cardiac rehabilitation. Trial registration number: ClinicalTrials.gov, NCT05292287. Registered on 22/03/2022.

Ex Vivo treatment of coronary artery endothelial cells with serum post-exercise training offers limited protection against in vitro exposure to FEC-T chemotherapy.

Background: Chemotherapy treatment for breast cancer associates with well-documented cardiovascular detriments. Exercise has shown promise as a potentially protective intervention against cardiac toxicity. However, there is a paucity of evidence for the benefits of exercise on the vasculature. Objectives: This study aimed to determine the effects of chemotherapy on the vascular endothelium; and if there are protective effects of serological alterations elicited by an exercise training intervention. Methods and Results: 15 women participated in a 12-week home-based exercise intervention consisting of three high-intensity interval sessions per week. Human coronary artery endothelial cells (HCAEC) were exposed to physiological concentrations of 5-fluorouracil, epirubicin, cyclophosphamide (FEC) and docetaxel to determine a dose-response. Twenty-4 hours prior to FEC and docetaxel exposure, HCAECs were preconditioned with serum collected pre- and post-training. Annexin V binding and cleaved caspase-3 were assessed using flow cytometry and wound repair by scratch assays. Chemotherapy exposure increased HCAEC Annexin V binding, cleaved caspase-3 expression in a dose-dependent manner; and inhibited wound repair. Compared to pre-training serum, conditioning HCAECs with post-training serum, reduced Annexin V binding (42% vs. 30%, p = 0.01) when exposed to FEC. For docetaxel, there were no within-group differences (pre-vs post-exercise) for Annexin V binding or cleaved caspase-3 expression. There was a protective effect of post-training serum on wound repair for 5-flurouracil (p = 0.03) only. Conclusion: FEC-T chemotherapy drugs cause significant damage and dysfunction of endothelial cells. Preconditioning with serum collected after an exercise training intervention, elicited some protection against the usual toxicity of FEC-T, when compared to control serum.

Association between atherogenic risk-modulating proteins and endothelium-dependent flow-mediated dilation in coronary artery disease patients.

PURPOSE: Endothelial dysfunction is an early and integral event in the development of atherosclerosis and coronary artery disease (CAD). Reduced NO bioavailability, oxidative stress, vasoconstriction, inflammation and senescence are all implicated in endothelial dysfunction. However, there are limited data examining associations between these pathways and direct in vivo bioassay measures of endothelial function in CAD patients. This study aimed to examine the relationships between in vivo measures of vascular function and the expression of atherogenic risk-modulating proteins in endothelial cells (ECs) isolated from the radial artery of CAD patients. METHODS: Fifty-six patients with established CAD underwent trans-radial catheterization. Prior to catheterization, radial artery vascular function was assessed using a) flow-mediated dilation (FMD), and b) exercise-induced dilation in response to handgrip (HE%). Freshly isolated ECs were obtained from the radial artery during catheterization and protein content of eNOS, NAD(P)H oxidase subunit NOX2, NFκB, ET-1 and the senescence markers p53, p21 and p16 were evaluated alongside nitrotyrosine abundance and eNOS Ser1177 phosphorylation. RESULTS: FMD was positively associated with eNOS Ser1177 phosphorylation (r = 0.290, P = 0.037), and protein content of p21 (r = 0.307, P = 0.027) and p16 (r = 0.426, P = 0.002). No associations were found between FMD and markers of oxidative stress, vasoconstriction or inflammation. In contrast to FMD, HE% was not associated with any of the EC proteins. CONCLUSION: These data revealed a difference in the regulation of endothelium-dependent vasodilation measured in vivo between patients with CAD compared to previously reported data in subjects without a clinical diagnosis, suggesting that eNOS Ser1177 phosphorylation may be the key to maintain vasodilation in CAD patients.

Post-exercise endothelial function is not associated with extracellular vesicle release in healthy young males.

Acute exercise can result in temporary decrease in endothelial functions, which may represent a transient period of risk. Numerous mechanisms underpinning these responses included release of extracellular vesicles (EVs) derived from apoptotic or activated endothelial cells and platelets. This study aims to compare the time course of endothelial responses to moderate-intensity continuous exercise (MICE) and high-intensity interval exercise (HIIE) and the associations with EV release. Eighteen young healthy males (age: 22.6 ± 3.7 years, BMI: 25.6 ± 2.5 m2/kg, and VO2peak: 38.6 ± 6.5 mL/kg/min) completed two randomly assigned exercises: HIIE (10 × 1 min-@-90% heart rate reserve (HRR) and 1 min passive recovery) and MICE (30 min-@-70% HRR) on a cycle ergometer. Flow-mediated dilation (FMD) was used to assess endothelial function and blood samples were collected to evaluate endothelial cell-derived EV (CD62E+) and platelet-derived EV (CD41a+), 10, 60, and 120 min before and after exercise. There were similar increases but different time courses (P = 0.017) in FMD (increased 10 min post-HIIE, P < 0.0001 and 60 min post-MICE, P = 0.038). CD62E+ remained unchanged (P = 0.530), whereas overall CD41a+ release was reduced 60 min post-exercise (P = 0.040). FMD was not associated with EV absolute release or change (P > 0.05). Acute exercise resulted in similar improvements, but different time course in FMD following either exercise. Whilst EVs were not associated with FMD, the reduction in platelet-derived EVs may represent a protective mechanism following acute exercise.

Elevated shear rate-induced by exercise increases eNOS ser1177 but not PECAM-1 Tyr713 phosphorylation in human conduit artery endothelial cells.

Although evidence demonstrates the fundamental role of shear stress in vascular health, predominantly through the release of nitric oxide (NO), the mechanisms by which endothelial cells (EC)s sense and transduce shear are poorly understood. In cultured ECs tyrosine phosphorylation of PECAM-1 has been shown to activate eNOS in response to shear stress. However, in the human skeletal muscle microcirculation PECAM-1 was not activated in response to exercise or passive leg movement. Given this contradiction, this study aimed to assess the effect of exercise on conduit artery PECAM-1 and eNOS activation in humans. Eleven males were randomised to two groups; 30 min of handgrip exercise (n = 6), or a time-control group (n = 5). Protein content of eNOS and PECAM-1, alongside eNOS Ser1177 and PECAM-1 Tyr713 phosphorylation were assessed in ECs obtained from the radial artery pre- and post-intervention. Handgrip exercise resulted in a 5-fold increase in mean shear rate in the exercise group, with no change in the control group (group*time, P < 0.001). There was a 54% increase in eNOS Ser1177 phosphorylation in the exercise group, when compared to control group (group*time, P = 0.016), but no change was reported in PECAM-1 Tyr713 phosphorylation in either group (group*time, P > 0.05). eNOS and PECAM-1 protein content were unchanged (group*time, P > 0.05). Our data show that exercise-induced elevations in conduit artery shear rate increase eNOS Ser1177 phosphorylation but not PECAM-1 Tyr713 phosphorylation. This suggests PECAM-1 phosphorylation may not be involved in the vascular response to acute but prolonged elevations in exercise-induced shear rate in conduit arteries of healthy, active men.

Perceptions of Antenatal Exercise in Pregnant Females and the Impact of COVID-19.

Exercise during pregnancy presents many benefits for the mother and baby. Yet, pregnancy is characterised by a decrease in exercise. Studies have reported barriers to antenatal exercise. The coronavirus (COVID-19) pandemic may have further exacerbated barriers to antenatal exercise as pregnant females faced many challenges. Rich, in-depth exploration into pregnant female's perceived barriers to antenatal exercise during COVID-19 is imperative. Questionnaires reporting physical activity levels were completed by all participants (n = 14). Semi-structured interviews were conducted between November 2020 and May 2021 in the UK. Interviews were analysed using thematic analysis and revealed four main themes: 'Perceptions of being an active person shaping activity levels in pregnancy', 'How do I know what is right? Uncertainty, seeking validation and feeling informed', 'Motivators to antenatal exercise' and 'A process of adaptations and adjustment'. Findings indicate that the COVID-19 pandemic exacerbated barriers to antenatal exercise and highlight the importance of direct psychosocial support and clear, trustworthy information. Findings also support the fundamental need for better education amongst healthcare professionals regarding antenatal exercise.

Polygenic mechanisms underpinning the response to exercise-induced muscle damage in humans: In vivo and in vitro evidence.

We investigated whether 20 candidate single nucleotide polymorphisms (SNPs) were associated with in vivo exercise-induced muscle damage (EIMD), and with an in vitro skeletal muscle stem cell wound healing assay. Sixty-five young, untrained Caucasian adults performed 120 maximal eccentric knee-extensions on an isokinetic dynamometer to induce EIMD. Maximal voluntary isometric/isokinetic knee-extensor torque, knee joint range of motion (ROM), muscle soreness, serum creatine kinase activity and interleukin-6 concentration were assessed before, directly after and 48 h after EIMD. Muscle stem cells were cultured from vastus lateralis biopsies from a separate cohort (n = 12), and markers of repair were measured in vitro. Participants were genotyped for all 20 SNPs using real-time PCR. Seven SNPs were associated with the response to EIMD, and these were used to calculate a total genotype score, which enabled participants to be segregated into three polygenic groups: 'preferential' (more 'protective' alleles), 'moderate', and 'non-preferential'. The non-preferential group was consistently weaker than the preferential group (1.93 ± 0.81 vs. 2.73 ± 0.59 N ∙ m/kg; P = 9.51 × 10-4 ) and demonstrated more muscle soreness (p = 0.011) and a larger decrease in knee joint ROM (p = 0.006) following EIMD. Two TTN-AS1 SNPs in linkage disequilibrium were associated with in vivo EIMD (rs3731749, p ≤ 0.005) and accelerated muscle stem cell migration into the artificial wound in vitro (rs1001238, p ≤ 0.006). Thus, we have identified a polygenic profile, linked with both muscle weakness and poorer recovery following EIMD. Moreover, we provide evidence for a novel TTN gene-cell-skeletal muscle mechanism that may help explain some of the interindividual variability in the response to EIMD.

Home-Based HIIT and Traditional MICT Prescriptions Improve Cardiorespiratory Fitness to a Similar Extent Within an Exercise Referral Scheme for At-Risk Individuals.

Exercise referral schemes (ERS) are used to promote physical activity within primary care. Traditionally, ERS are conducted in a gym or leisure-center setting, with exercise prescriptions based on moderate-intensity continuous training (MICT). Home-based high-intensity interval training (Home-HIIT) has the potential to reduce perceived barriers to exercise, including lack of time and access to facilities, compared to traditional MICT prescription used with ERS and improve health related outcomes. We hypothesized that Home-HIIT would mediate greater improvement in cardiorespiratory fitness (CRF) by virtue of greater adherence and compliance to the exercise prescription, compared to MICT. Methods: Patients enrolled on an ERS (Liverpool, United Kingdom) were recruited for a pragmatic trial. Participants self-selected either 12 weeks of MICT (45-135 min/week at 50-70% HRmax) or Home-HIIT (4-9 min × 1 min intervals at ≥80% of HRmax, interspersed with 1 min rest). The primary outcome was the change in CRF (VO2 peak) at post-intervention (12 weeks) and follow-up (3-month post intervention), using intention-to-treat analysis. Results: 154 participants (age 48 ± 10y; BMI 30.5 ± 6.1 kg/m2) were recruited between October 2017 and March 2019, 87 (56%) participants chose Home-HIIT and 67 (44%) MICT. VO2 peak increased post-intervention in both groups (MICT 3.9 ± 6.0 ml.kg-1.min-1, Home-HIIT 2.8 ± 4.5 ml.kg-1.min-1, P < 0.001), and was maintained at follow-up (P < 0.001). Fat mass was only reduced post MICT (MICT -1.5 ± 6.3 kg, P < 0.05, Home-HIIT -0.2 ± 2.0 kg, P = 1.00), but the reduction was not maintained at follow-up (MICT -0.6 ± 5.1 kg, Home-HIIT 0.0 ± 2.2 kg, P > 0.05). Adherence to the prescribed programs was similar (MICT 48 ± 35%, Home-HIIT 39 ± 36%, P = 0.77). Conclusion: This is the first study to evaluate the use of Home-HIIT for individuals in a primary care setting. Contrary to our hypothesis, adherence to both exercise prescriptions was poor, and CRF improved to a similar extent in both groups with improvements maintained at 3-month follow-up. We provide evidence that, although not superior, Home-HIIT could be an effective and popular additional exercise choice for patients within primary care based ERS. Clinical Trial Registration: [ClinicalTrials.gov], identifier [NCT04553614].

Mobile Health Biometrics to Enhance Exercise and Physical Activity Adherence in Type 2 Diabetes (MOTIVATE-T2D): protocol for a feasibility randomised controlled trial.

INTRODUCTION: Exercise and physical activity (PA) are fundamental to the treatment of type 2 diabetes. Current exercise and PA strategies for newly diagnosed individuals with type 2 diabetes are either clinically effective but unsuitable in routine practice (supervised exercise) or suitable in routine practice but clinically ineffective (PA advice). Mobile health (mHealth) technologies, offering biometric data to patients and healthcare professionals, may bridge the gap between supervised exercise and PA advice, enabling patients to engage in regular long-term physically active lifestyles. This feasibility randomised controlled trial (RCT) will evaluate the use of mHealth technology when incorporated into a structured home-based exercise and PA intervention, in those recently diagnosed with type 2 diabetes. METHODS AND ANALYSIS: This feasibility multicentre, parallel group RCT will recruit 120 individuals with type 2 diabetes (diagnosis within 5-24 months, aged 40-75 years) in the UK (n=60) and Canada (n=60). Participants will undertake a 6-month structured exercise and PA intervention and be supported by an exercise specialist (active control). The intervention group will receive additional support from a smartwatch and phone app, providing real-time feedback and enabling improved communication between the exercise specialist and participant. Primary outcomes are recruitment rate, adherence to exercise and loss to follow-up. Secondary outcomes include a qualitative process evaluation and piloting of potential clinical outcome measures for a future RCT. ETHICS AND DISSEMINATION: The trial was approved in the UK by the South East Scotland Research Ethics Committee 01 (20/SS/0101) and in Canada by the Clinical Research Ethics Board of the University of British Columbia (H20-01936), and is being conducted in accordance with the Declaration of Helsinki and Good Clinical Practice. Results will be published in peer-reviewed journals and presented at national and international scientific meetings. TRIAL REGISTRATION NUMBERS: ISRCTN14335124; ClinicalTrials.gov: NCT04653532.

Evidence-based vs. social media based high-intensity interval training protocols: Physiological and perceptual responses.

OBJECTIVE: High intensity interval training (HIIT) is a time-efficient exercise modality to improve cardiorespiratory fitness, and has recently been popularised by social media influencers. However, little is known regarding acute physiological and perceptual responses to these online protocols compared to HIIT protocols used within research. The aim was to investigate acute physiological, perceptual and motivational responses to two HIIT protocols popular on social media, and compare these to two evidence-based protocols. METHODS: Twenty-seven recreationally active (>1 exercise session /week) participants (Age: 22±3y, BMI: 24.3±2.4) completed a randomised cross-over study, whereby each participant completed four HIIT protocols, two already established in research (Ergo-60:60 (cycling 10x60s at 100%Wmaxwith 60s rest), BW-60:60 (body-weight exercises 10x60swith 60s rest)) and two promoted on social media (SM-20:10 (body-weight exercises 20x20swith 10s rest) and SM-40:20 (body-weight exercises 15x40s with 20s rest)). Blood lactate, heart rate (HR), feeling scale (FS), felt arousal scale (FSA), enjoyment and perceived competence were measured in response to each protocol. RESULTS: Significant differences were observed between BW-60:60 and SM-20:10 for the proportion of intervals meeting the ACSM high-intensity exercise criterion (>80% of HRmax) (BW-60:60 93±10%, SM-20:10 74±20%, P = 0.039) and change in lactate (BW-60:60 +7.8±3.7mmol/L, SM-20:10 +5.5±2.6mmol/L, P = 0.001). The percentage of time spent above the criterion HR was also significantly lower in SM-20:10 compared to all other protocols (Ergo-60:60 13.9±4.9min, BW-60:60 13.5±3.5min, SM-40:20 12.1±2.4min, SM-20:10 7.7±3.1, P<0.05). No differences were observed in lowest reported FS between protocols (P = 0.268), but FS decreased linearly throughout Ergo-60:60 and BW-60:60 (first vs. last interval P<0.05), but not in SM-20:10 or SM-40:20 (P>0.05). Enjoyment was higher upon completion of BW-60:60 compared to Ergo-60:60 and SM-40:20 (P<0.05). CONCLUSIONS: This study shows that HIIT protocols available on social media offer an interesting real-world alternative for promoting exercise participation. Future studies should continue to investigate these highly popular and practical HIIT protocols.

Carbohydrate improves exercise capacity but does not affect subcellular lipid droplet morphology, AMPK and p53 signalling in human skeletal muscle.

KEY POINTS: Muscle glycogen and intramuscular triglycerides (IMTG, stored in lipid droplets) are important energy substrates during prolonged exercise. Exercise-induced changes in lipid droplet (LD) morphology (i.e. LD size and number) have not yet been studied under nutritional conditions typically adopted by elite endurance athletes, that is, after carbohydrate (CHO) loading and CHO feeding during exercise. We report for the first time that exercise reduces IMTG content in both central and peripheral regions of type I and IIa fibres, reflective of decreased LD number in both fibre types whereas reductions in LD size were exclusive to type I fibres. Additionally, CHO feeding does not alter subcellular IMTG utilisation, LD morphology or muscle glycogen utilisation in type I or IIa/II fibres. In the absence of alterations to muscle fuel selection, CHO feeding does not attenuate cell signalling pathways with regulatory roles in mitochondrial biogenesis. ABSTRACT: We examined the effects of carbohydrate (CHO) feeding on lipid droplet (LD) morphology, muscle glycogen utilisation and exercise-induced skeletal muscle cell signalling. After a 36 h CHO loading protocol and pre-exercise meal (12 and 2 g kg-1 , respectively), eight trained males ingested 0, 45 or 90 g CHO h-1 during 180 min cycling at lactate threshold followed by an exercise capacity test (150% lactate threshold). Muscle biopsies were obtained pre- and post-completion of submaximal exercise. Exercise decreased (P < 0.01) glycogen concentration to comparable levels (∼700 to 250 mmol kg-1 DW), though utilisation was greater in type I (∼40%) versus type II fibres (∼10%) (P < 0.01). LD content decreased in type I (∼50%) and type IIa fibres (∼30%) (P < 0.01), with greater utilisation in type I fibres (P < 0.01). CHO feeding did not affect glycogen or IMTG utilisation in type I or II fibres (all P > 0.05). Exercise decreased LD number within central and peripheral regions of both type I and IIa fibres, though reduced LD size was exclusive to type I fibres. Exercise induced (all P < 0.05) comparable AMPKThr172 (∼4-fold), p53Ser15 (∼2-fold) and CaMKIIThr268 phosphorylation (∼2-fold) with no effects of CHO feeding (all P > 0.05). CHO increased exercise capacity where 90 g h-1 (233 ± 133 s) > 45 g h-1 (156 ± 66 s; P = 0.06) > 0 g h-1 (108 ± 54 s; P = 0.03). In conditions of high pre-exercise CHO availability, we conclude CHO feeding does not influence exercise-induced changes in LD morphology, glycogen utilisation or cell signalling pathways with regulatory roles in mitochondrial biogenesis.

Impact of catheterization on shear-mediated arterial dilation in healthy young men.

PURPOSE: Animal studies have shown that endothelial denudation abolishes vasodilation in response to increased shear stress. Interestingly, shear-mediated dilation has been reported to be reduced, but not abolished, in coronary artery disease (CAD) patients following catheterization. However, it is not known whether this resulted from a priori endothelial dysfunction in this diseased population. In this study, we evaluated shear-mediated dilation following catheterization in healthy young men. METHODS: Twenty-six (age: 24.4 ± 3.8 years, BMI: 24.3 ± 2.8 kg m-2, VO2peak: 50.5 ± 8.8 ml/kg/min) healthy males underwent unilateral transradial catheterization. Shear-mediated dilation of both radial arteries was measured using flow-mediated dilation (FMD) pre-, and 7 days post-catheterization. RESULTS: FMD was reduced in the catheterized arm [9.3 ± 4.1% to 4.3 ± 4.1% (P < 0.001)] post-catheterization, whereas no change was observed in the control arm [8.4 ± 3.8% to 7.3 ± 3.8% (P = 0.168)]. FMD was completely abolished in the catheterized arm in five participants. Baseline diameter (P = 0.001) and peak diameter during FMD (P = 0.035) were increased in the catheterized arm 7 days post-catheterization (baseline: 2.3 ± 0.3 to 2.6 ± 0.2 mm, P < 0.001, peak: 2.5 ± 0.3 to 2.7 ± 0.3 mm, P = 0.001), with no change in the control arm (baseline: 2.3 ± 0.3 to 2.3 ± 0.3 mm, P = 0.288, peak: 2.5 ± 0.3 to 2.5 ± 0.3 mm, P = 0.608). CONCLUSION: This is the first study in young healthy individuals with intact a priori endothelial function to provide evidence of impaired shear-mediated dilation following catheterization. When combined with earlier studies in CAD patients, our data suggest the catheterization impairs artery function in humans.

Exercise-induced vasodilation is not impaired following radial artery catheterization in coronary artery disease patients.

Diagnosis and treatment for coronary artery disease (CAD) often involves angiography and/or percutaneous coronary intervention. However, the radial artery catheterization required during both procedures may result in acute artery dysfunction/damage. While exercise-based rehabilitation is recommended for CAD patients following catheterization, it is not known if there is a period when exercise may be detrimental due to catheter-induced damage. Animal studies have demonstrated exercise-induced paradoxical vasoconstriction postcatheterization. This study aimed to examine arterial responses to acute exercise following catheterization. Thirty-three CAD patients (65.8 ± 7.3 yr, 31.5 ± 6.3 kg/m2, 82% men) undergoing transradial catheterization were assessed before and 1 wk postcatheterization. Radial artery (RA) diameter and shear rate were assessed during handgrip exercise (HE), in both the catheterized (CATH) and control (CON) arms. Endothelial function was also assessed via simultaneous bilateral radial flow-mediated dilation (FMD) at both time points. We found that the increase in RA diameter and shear stress in response to HE (P < 0.0001) was maintained postcatheterization in both the CATH and CON arms, whereas FMD following catheterization was impaired in the CATH [6.5 ± 3.3 to 4.7 ± 3.5% (P = 0.005)] but not in the CON [6.2 ± 2.6 to 6.4 ± 3.5% (P = 0.797)] limb. While endothelial dysfunction, assessed by FMD, was apparent 1 wk postcatheterization, the ability of the RA to dilate in response to exercise was not impaired. The impact of catheterization and consequent endothelial denudation on vascular dys/function in humans may therefore be stimulus specific, and a highly level of redundancy appears to exist that preserves exercise-mediated vasodilator responses.NEW & NOTEWORTHY Despite depressed flow-mediated endothelium-dependent dilation following catheterization-induced damage, radial artery responses to handgrip exercise were preserved. This suggests that arterial responses to catheterization may be stimulus specific and that redundant mechanisms may compensate for vasodilator impairment during exercise. This has implications for exercise-based rehabilitation after catheterization.

High-Fat Overfeeding Impairs Peripheral Glucose Metabolism and Muscle Microvascular eNOS Ser1177 Phosphorylation.

CONTEXT: The mechanisms responsible for dietary fat-induced insulin resistance of skeletal muscle and its microvasculature are only partially understood. OBJECTIVE: To determine the impact of high-fat overfeeding on postprandial glucose fluxes, muscle insulin signaling, and muscle microvascular endothelial nitric oxide synthase (eNOS) content and activation. DESIGN: Fifteen non-obese volunteers consumed a high-fat (64%) high-energy (+47%) diet for 7 days. Experiments were performed before and after the diet. Stable isotope tracers were used to determine glucose fluxes in response to carbohydrate plus protein ingestion. Muscle insulin signaling was determined as well as the content and activation state of muscle microvascular eNOS. RESULTS: High-fat overfeeding impaired postprandial glycemic control as demonstrated by higher concentrations of glucose (+11%; P = 0.004) and insulin (+19%; P = 0.035). Carbohydrate plus protein ingestion suppressed endogenous glucose production to a similar extent before and after the diet. Conversely, high-fat overfeeding reduced whole-body glucose clearance (-16%; P = 0.021) and peripheral insulin sensitivity (-26%; P = 0.006). This occurred despite only minor alterations in skeletal muscle insulin signaling. High-fat overfeeding reduced eNOS content in terminal arterioles (P = 0.017) and abolished the increase in eNOS Ser1177 phosphorylation that was seen after carbohydrate plus protein ingestion. CONCLUSION: High-fat overfeeding impaired whole-body glycemic control due to reduced glucose clearance, not elevated endogenous glucose production. The finding that high-fat overfeeding abolished insulin-mediated eNOS Ser1177 phosphorylation in the terminal arterioles suggests that impairments in the vasodilatory capacity of the skeletal muscle microvasculature may contribute to early dietary fat-induced impairments in glycemic control.

Decreased Aerobic Exercise Capacity After Long-Term Remission From Cushing Syndrome: Exploration of Mechanisms.

BACKGROUND: Although major improvements are achieved after cure of Cushing syndrome (CS), fatigue and decreased quality of life persist. This is the first study to measure aerobic exercise capacity in patients in remission of CS for more than 4 years in comparison with matched controls, and to investigate whether the reduction in exercise capacity is related to alterations in muscle tissue. METHODS: Seventeen patients were included. A control individual, matched for sex, estrogen status, age, body mass index, smoking, ethnicity, and physical activity level was recruited for each patient. Maximal aerobic capacity (VO2peak) was assessed during incremental bicycle exercise to exhaustion. In 8 individually matched patients and controls, a percutaneous muscle biopsy was obtained and measures were made of cross-sectional areas, capillarization, and oxphos complex IV (COXIV) protein content as an indicator of mitochondrial content. Furthermore, protein content of endothelial nitric oxide synthase (eNOS) and eNOS phosphorylated on serine1177 and of the NAD(P)H-oxidase subunits NOX2, p47phox, and p67phox were measured in the microvascular endothelial layer. FINDINGS: Patients showed a lower mean VO2peak (SD) (28.0 [7.0] vs 34.8 [7.9] ml O2/kg bw/min, P < .01), maximal workload (SD) (176 [49] vs 212 [67] watt, P = .01), and oxygen pulse (SD) (12.0 [3.7] vs 14.8 [4.2] ml/beat, P < .01) at VO2peak. No differences were seen in muscle fiber type-specific cross-sectional area, capillarization measures, mitochondrial content, and protein content of eNOS, eNOS-P-ser1177, NOX2, p47phox, and p67phox. INTERPRETATION: Because differences in muscle fiber and microvascular outcome measures are not statistically significant, we hypothesize that cardiac dysfunction, seen in active CS, persists during remission and limits blood supply to muscles.

Capillary facilitation of skeletal muscle function in health and disease.

Skeletal muscle is highly vascularized, with perfusion being tightly regulated to meet wide-ranging metabolic demands. For decades, the capillary supply has been explored mainly in terms of evaluating the capillary numbers and their function in the supply of oxygen and substrates and the removal of metabolic byproducts. This review will focus on recent discoveries concerning the role played by capillaries in facilitating other aspects of cell regulation and maintenance, in health and disease, as well as alterations during the aging process. Novelty Capillaries play a central role in the coordination of the vascular response that controls blood flow during contraction and the cellular responses to which they feed into. Nitric oxide is an important regulatory compound within the cardiovascular system, and a significant contributor to skeletal muscle capillary angiogenesis and vasodilatory response to agonists. The microvascular network between muscle fibres may play a critical role in the distribution of signalling factors necessary for optimal muscle satellite cell function.