Impact of eight weeks of repeated ischaemic preconditioning on brachial artery and cutaneous microcirculatory function in healthy males

Background Ischaemic preconditioning has well-established cardiac and vascular protective effects. Short interventions (one week) of daily ischaemic preconditioning episodes improve conduit and microcirculatory function. This study examined whether a longer (eight weeks) and less frequent (three per week) protocol of repeated ischaemic preconditioning improves vascular function. Methods Eighteen males were randomly allocated to either ischaemic preconditioning (22.4 ± 2.3 years, 23.7 ± 3.1 kg/m2) or a control intervention (26.0 ± 4.8 years, 26.4 ± 1.9 kg/m2). Brachial artery endothelial-dependent (FMD), forearm cutaneous microvascular function and cardiorespiratory fitness were assessed at zero, two and eight weeks. Results A greater improvement in FMD was evident following ischaemic preconditioning training compared with control at weeks 2 (2.24% (0.40, 4.08); p=0.02) and 8 (1.11% (0.13, 2.10); p=0.03). Repeated ischaemic preconditioning did not change cutaneous microcirculatory function or fitness. Conclusions These data indicate that a feasible and practical protocol of regular ischaemic preconditioning episodes improves endothelial function in healthy individuals within two weeks, and these effects persist following repeated ischaemic preconditioning for eight weeks

Reduced physical activity in young and older adults: metabolic and musculoskeletal implications

Background: Although the health benefits of regular physical activity and exercise are well established and have been incorporated into national public health recommendations, there is a relative lack of understanding pertaining to the harmful effects of physical inactivity. Experimental paradigms including complete immobilization and bed rest are not physiologically representative of sedentary living. A useful ‘real-world’ approach to contextualize the physiology of societal downward shifts in physical activity patterns is that of short-term daily step reduction. Results: Step-reduction studies have largely focused on musculoskeletal and metabolic health parameters, providing relevant disease models for metabolic syndrome, type 2 diabetes (T2D), nonalcoholic fatty liver disease (NAFLD), sarcopenia and osteopenia/osteoporosis. In untrained individuals, even a short-term reduction in physical activity has a significant impact on skeletal muscle protein and carbohydrate metabolism, causing anabolic resistance and peripheral insulin resistance, respectively. From a metabolic perspective, short-term inactivity-induced peripheral insulin resistance in skeletal muscle and adipose tissue, with consequent liver triglyceride accumulation, leads to hepatic insulin resistance and a characteristic dyslipidaemia. Concomitantly, various inactivity-related factors contribute to a decline in function; a reduction in cardiorespiratory fitness, muscle mass and muscle strength. Conclusions: Physical inactivity maybe particularly deleterious in certain patient populations, such as those at high risk of T2D or in the elderly, considering concomitant sarcopenia or osteoporosis. The effects of short-term physical inactivity (with step reduction) are reversible on resumption of habitual physical activity in younger people, but less so in older adults. Nutritional interventions and resistance training offer potential strategies to prevent these deleterious metabolic and musculoskeletal effects. Impact: Individuals at high risk of/with cardiometabolic disease and older adults may be more prone to these acute periods of inactivity due to acute illness or hospitalization. Understanding the risks is paramount to implementing countermeasures

Compensatory changes in energy balance during dapagliflozin treatment in type 2 diabetes mellitus: a randomised double-blind, placebo-controlled, cross-over trial (ENERGIZE)-study protocol.

INTRODUCTION: Sodium glucose cotransporter 2 (SGLT2) inhibitors are effective blood-glucose-lowering medications with beneficial effects on body weight in patients with type 2 diabetes mellitus (T2DM). However, observed weight loss is less than that predicted from quantified glycosuria, suggesting a compensatory increase in energy intake or a decrease in energy expenditure. Studies using dual-energy X-ray absorptiometry (DEXA) have suggested most body weight change is due to loss of adipose tissue, but organ-specific changes in fat content (eg, liver, skeletal muscle) have not been determined. In this randomised, double-blind, placebo-controlled crossover study, we aim to study the compensatory changes in energy intake, eating behaviour and energy expenditure accompanying use of the SGLT2 inhibitor, dapagliflozin. Additionally, we aim to quantify changes in fat distribution using MRI, in liver fat using proton magnetic resonance spectroscopy ((1)H-MRS) and in central nervous system (CNS) responses to food images using blood oxygen level dependent (BOLD) functional MRI (fMRI). METHODS AND ANALYSIS: This outpatient study will evaluate the effect of dapagliflozin (10 mg), compared with placebo, on food intake and energy expenditure at 7 days and 12 weeks. 52 patients with T2DM will be randomised to dapagliflozin or placebo for short-term and long-term trial interventions in a within participants, crossover design. The primary outcome is the difference in energy intake during a test meal between dapagliflozin and placebo. Intake data are collected automatically using a customised programme operating a universal eating monitor (UEM). Secondary outcomes include (1) measures of appetite regulation including rate of eating, satiety quotient, appetite ratings (between and within meals), changes in CNS responses to food images measured using BOLD-fMRI, (2) measures of energy expenditure and (3) changes in body composition including changes in liver fat and abdominal visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT). ETHICAL APPROVAL: This study has been approved by the North West Liverpool Central Research Ethics Committee (14/NW/0340) and is conducted in accordance with the Declaration of Helsinki and the Good Clinical Practice (GCP). TRIAL REGISTRATION NUMBER: ISRCTN14818531. EUDRACT number 2013-004264-60

REPEATED WARM WATER IMMERSION INDUCES SIMILAR CEREBROVASCULAR ADAPTATIONS TO 8-WEEKS OF MODERATE-INTENSITY EXERCISE TRAINING IN FEMALES

Exercise training has potential to positively impact cerebrovascular function in healthy and diseased individuals. Passive heat training using warm water immersion has recently been shown to enhance systemic vascular function including the cerebrovascular response to heating. We suggest that a passive heating intervention can be a useful adjunct or alternative to exercise training. Our aim was to directly compare the effects of exercise with warm water immersion training on cerebrovascular and thermoregulatory function. 18 females (25±5y) performed 8-weeks of moderate-intensity cycling (70% HRmax) or warm-water immersion (42°C) for 30 min three times per week. Brachial artery flow-mediated dilation (FMD) and cardiorespiratory fitness were measured prior to and following both interventions. A passive heat stress was employed to obtain temperature thresholds (Tb) and sensitivities for chest and forearm sweat rate (SR) and cutaneous vasodilation (CVC). Middle cerebral artery velocity (MCAv) was measured at rest and throughout heat stress. FMD (P=0.003) and VO2peak (P<0.001) improved following both interventions. MCAv and cerebrovascular conductance were higher at rest (P<0.001 and 0.05, respectively) and during passive heating (P<0.001 and <0.001, respectively) following both interventions. Chest and forearm SR occurred at a lower Tb post-intervention with no difference between interventions. Chest and forearm SR sensitivity were increased after both interventions with no differences between interventions at the forearm but a larger increase at the chest (P<0.001) following water immersion compared to exercise training. Chest and forearm CVC occurred at a lower Tb (P<0.001) following both interventions with no differences between interventions or over time. Warm water immersion training elicits favourable and similar cerebrovascular, conduit- and thermoregulatory adaptations compared to a period of moderate-intensity exercise training over 8-weeks

EXERCISE TRAINING REDUCES THE FREQUENCY OF MENOPAUSAL HOT FLUSHES BY IMPROVING THERMOREGULATORY CONTROL

Objectives: Post-menopausal hot flushes occur due to a reduction in oestrogen production causing thermoregulatory and vascular dysfunction. Exercise training enhances thermoregulatory control of sweating, skin and brain blood flow. We aimed to determine if improving thermoregulatory control and vascular function with exercise training alleviated hot flushes. Methods: Twenty one symptomatic females completed a 7-day hot flush questionnaire and underwent brachial artery flow-mediated dilation and a cardiorespiratory fitness test. Sweat rate and skin blood flow temperature thresholds and sensitivities, and middle cerebral artery velocity (MCAv) was measured during passive heating. Females performed 16-weeks of supervised exercise training or control, and measurements were repeated. Results: There was a greater improvement in cardiorespiratory fitness (4.45 ml•kg-1•min-1 (95% CI: 1.87, 8.16; P=0.04) and reduced hot flush frequency [48 hot flushes•week (39, 56) P<0.001] following exercise compared to control. Exercise reduced basal core temperature [0.14°C (0.01, 0.27) P=0.03] and increased basal MCAv [2.8 cm/s (1.0 to 5.2) P=0.04] compared to control. Sweat rate and skin blood flow thresholds occurred ~0.19 and 0.17°C earlier, alongside improved sweating sensitivity with exercise. MCAv decreased during heating [P<0.005], but was maintained 4.5 cm/s (3.6, 5.5 P<0.005) higher during heating following exercise compared to control [0.6 cm/s (-0.4, 1.4)]. Conclusions: Exercise training that improves cardiorespiratory fitness reduces self-reported hot flushes. Improvements are likely mediated through greater thermoregulatory control in response to increases in core temperature and enhanced vascular function in the cutaneous and cerebral circulations

Metabolically healthy and unhealthy obesity: differential effects on myocardial function according to metabolic syndrome, rather than obesity.

BACKGROUND: The term 'metabolically healthy obese (MHO)' is distinguished using body mass index (BMI), yet BMI is a poor index of adiposity. Some epidemiological data suggest that MHO carries a lower risk of cardiovascular disease (CVD) or mortality than being normal weight yet metabolically unhealthy. OBJECTIVES: We aimed to undertake a detailed phenotyping of individuals with MHO by using imaging techniques to examine ectopic fat (visceral and liver fat deposition) and myocardial function. We hypothesised that metabolically unhealthy individuals (irrespective of BMI) would have adverse levels of ectopic fat and myocardial dysfunction compared with MHO individuals. SUBJECTS: Individuals were categorised as non-obese or obese (BMI ⩾30 kg m(-2)) and as metabolically healthy or unhealthy according to the presence or absence of metabolic syndrome. METHODS: Sixty-seven individuals (mean±s.d.: age 49±11 years) underwent measurement of (i) visceral, subcutaneous and liver fat using magnetic resonance imaging and proton magnetic resonance spectroscopy, (ii) components of metabolic syndrome, (iii) cardiorespiratory fitness and (iv) indices of systolic and diastolic function using tissue Doppler echocardiography. RESULTS: Cardiorespiratory fitness was similar between all groups; abdominal and visceral fat was highest in the obese groups. Compared with age- and BMI-matched metabolically healthy counterparts, the unhealthy (lean or obese) individuals had higher liver fat and decreased early diastolic strain rate, early diastolic tissue velocity and systolic strain indicative of subclinical systolic and diastolic dysfunction. The magnitude of dysfunction correlated with the number of components of metabolic syndrome but not with BMI or with the degree of ectopic (visceral or liver) fat deposition. CONCLUSIONS: Myocardial dysfunction appears to be related to poor metabolic health rather than simply BMI or fat mass. These data may partly explain the epidemiological evidence on CVD risk relating to the different obesity phenotypes

Effects of physical activity on vascular function in autoimmune rheumatic diseases: A systematic review and meta-analysis

Objectives: To summarize existing evidence and quantify the effects of physical activity on vascular function and structure in autoimmune rheumatic diseases (ARDs). Methods: Databases were searched (through March 2020) for clinical trials evaluating the effects of physical activity interventions on markers of micro- and macrovascular function and macrovascular structure in ARDs. Studies were combined using random effects meta-analysis, which was conducted using Hedges' g. Meta-analyses were performed on each of the following outcomes: microvascular function [i.e. skin blood flow or vascular conductance responses to acetylcholine (ACh) or sodium nitropusside (SNP) administration]; macrovascular function [i.e. brachial flow-mediated dilation (FMD%) or brachial responses to glyceryl trinitrate (GTN%); and macrovascular structure [i.e. aortic pulse wave velocity (PWV)]. Results: Ten studies (11 trials) with a total of 355 participants were included in this review. Physical activity promoted significant improvements in microvascular [skin blood flow responses to ACh, g = 0.92 (95% CI 0.42, 1.42)] and macrovascular function [FMD%, g = 0.94 (95% CI 0.56, 1.02); GTN%, g = 0.53 (95% CI 0.09, 0.98)]. Conversely, there was no evidence for beneficial effects of physical activity on macrovascular structure [PWV, g = -0.41 (95% CI -1.13, 0.32)]. Conclusions: Overall, the available clinical trials demonstrated a beneficial effect of physical activity on markers of micro- and macrovascular function but not on macrovascular structure in patients with ARDs. The broad beneficial impact of physical activity across the vasculature identified in this review support its role as an effective non-pharmacological management strategy for patients with ARDs

Physical Activity and Sedentary Time: Association with Metabolic Health and Liver Fat.

INTRODUCTION/PURPOSE: To investigate whether a) lower levels of daily physical activity (PA) and greater sedentary time accounted for contrasting metabolic phenotypes (higher liver fat/presence of metabolic syndrome [MetS+] vs lower liver fat/absence of metabolic syndrome [MetS-]) in individuals of similar BMI and b) the association of sedentary time on metabolic health and liver fat. METHODS: Ninety-eight habitually active participants (53 female, 45 male; age 39±13 years; BMI 26.9±5.1 kg/m), underwent assessments of PA (SenseWear armband; wear time ~98%), cardio-respiratory fitness (V[Combining Dot Above]O2 peak), body composition (MRI and MRS) and multi-organ insulin sensitivity (OGTT). We undertook a) cross-sectional analysis comparing four groups: non-obese or obese, with and without metabolic syndrome (MetS+ vs MetS-) and b) univariate and multivariate regression for sedentary time and other levels of PA in relation to liver fat. RESULTS: Light, moderate and vigorous PA did not account for differences in metabolic health between individuals, whether non-obese or obese, although MetS+ individuals were more sedentary, with a higher number, and prolonged bouts (~1-2 hours). Overall, sedentary time, average daily METS and V[Combining Dot Above]O2 peak were each independently associated with liver fat percentage. Each additional hour of daily sedentary time was associated with a 1.15% (95% CI, 1.14-1.50%) higher liver fat content. CONCLUSIONS: Greater sedentary time, independent of other levels of PA, is associated with being metabolically unhealthy; even in habitually active people, lesser sedentary time, and higher cardio-respiratory fitness and average daily METS is associated with lower liver fat.This is an open access article distributed under the Creative Commons Attribution License 4.0 (CCBY), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited

Seven day remote ischaemic preconditioning improves endothelial function in patients with type 2 diabetes mellitus: a randomised pilot study

Remote ischaemic preconditioning (rIPC) may improve cardiac/cerebrovascular outcomes of ischaemic events. Ischaemic damage caused by cardiovascular/cerebrovascular disease are primary causes of mortality in type 2 diabetes mellitus (T2DM). Due to the positive effects from a bout of rIPC within the vasculature, we explored if daily rIPC could improve endothelial and cerebrovascular function. The aim of this pilot study was to obtain estimates for the change in conduit artery and cerebrovascular function following a 7-day rIPC intervention. Methods: Twenty-one patients with T2DM were randomly allocated to either 7-day daily upper-arm rIPC (4x5 min 220 mmHg, interspaced by 5-min reperfusion) or control. We examined peripheral endothelial function using flow mediated dilation (FMD) before and after ischemia-reperfusion injury (IRI, 20 min forearm ischaemic-20 min reperfusion) and cerebrovascular function, assessed by dynamic cerebral autoregulation (dCA) at three time points; pre, post and 8 days post intervention. Results: For exploratory purposes, we performed statistical analysis on our primary comparison (pre-to-post) to provide an estimate of the change in the primary and secondary outcome variables. Using pre-intervention data as a covariate, the change from pre-post in FMD was 1.3% (95%CI: 0.69 to 3.80; P=0.09) and 0.23 %cm s-1 %.mmHg-1mm Hg/% (-0.12, 0.59; P=0.18) in dCA normalised gain with rIPC versus control. Based upon this, a sample size of 20 and 50 for FMD and normalised gain, respectively, in each group would provide 90% power to detect statistically significant (P&lt;0.05) between-group difference in a randomised controlled trial. Conclusion: We provide estimates of sample size for a randomised control trial exploring the impact of daily rIPC for 7 days on peripheral endothelial and cerebrovascular function. The directional changes outline from our pilot study suggest peripheral endothelial function can be enhanced by daily rIPC in patients with T2DM

A systematic review of interventions to increase physical activity and reduce sedentary behaviour following bariatric surgery.

BACKGROUND: Bariatric surgery promotes weight loss and improves co-morbid conditions, with patients who are more physically active having better outcomes. However, levels of physical activity and sedentary behaviour often remain unchanged following surgery. OBJECTIVES: To identify interventions and components thereof that are able to facilitate changes in physical activity and sedentary behaviour. ELIGIBILITY: Physical activity and/or sedentary behaviour must have been measured, pre and post intervention, in patients who have undergone bariatric surgery. STUDY APPRAISAL AND SYNTHESIS METHODS: Four databases were searched with key-words. Two researchers conducted paper screening, data extraction and risk-of-bias assessment. RESULTS: Twelve studies were included; eleven were randomised. Two were delivered presurgery and ten postsurgery; five found positive effect. Moderate to vigorous physical activity increased in three studies, two of which also found a significant increase in step count. The fourth found a significant increase in strenuous activity and the fifth a significant increase in metabolic equivalent of task/day and reduced time spent watching television. LIMITATIONS: Meta-analysis could not be conducted due to heterogeneity of outcomes and the tools used. CONCLUSION AND IMPLICATIONS OF KEY FINDINGS: This review has identified interventions and components thereof that were able to provoke positive effect. However, intervention and control conditions were not always well described particularly in terms of behaviour change techniques and the rationale for their use. SYSTEMATIC REVIEW REGISTRATION NUMBER: PROSPERO (CRD42019121372)