The most common non-pharmacological intervention for both peripheral and cerebral vascular health is regular physical activity (e.g., exercise training), which improves function across a range of exercise intensities and modalities. Numerous non-exercising approaches have also been suggested to improved vascular function, including repeated ischemic preconditioning (IPC); heat therapy such as hot water bathing and sauna; and pneumatic compression. Chronic adaptive responses have been observed across a number of these approaches, yet the precise mechanisms that underlie these effects in humans are not fully understood. Acute increases in blood flow and circulating signalling factors that induce responses in endothelial function are likely to be key moderators driving these adaptations. While the impact on circulating factors and environmental mechanisms for adaptation may vary between approaches, in essence, they all centre around acutely elevating blood flow throughout the circulation and stimulating improved endothelium-dependent vascular function and ultimately vascular health. Here, we review our current understanding of the mechanisms driving endothelial adaptation to repeated exposure to elevated blood flow, and the interplay between this response and changes in circulating factors. In addition, we will consider the limitations in our current knowledge base and how these may be best addressed through the selection of more physiologically relevant experimental models and research. Ultimately, improving our understanding of the unique impact that non-pharmacological interventions have on the vasculature will allow us to develop superior strategies to tackle declining vascular function across the lifespan, prevent avoidable vascular-related disease, and alleviate dependency on drug-based interventions.

Exercise elicits acute increases in cerebral blood flow velocity (CBFv) and provokes long-term beneficial effects on CBFv, thereby reducing cerebrovascular risk. Acute exposure to a cold stimulus also increases CBFv. We compared the impact of exercise training in cold and thermoneutral environments on CFBv, cerebrovascular function and peripheral endothelial function. Twenty-one (16 males, 22 +/- 5 years) individuals were randomly allocated to either a cold (5 degrees C) or thermoneutral (15 degrees C) exercise intervention. Exercise consisted of 50-min cycling at 70% heart rate max, three times per week for eight weeks. Transcranial Doppler was used to determine pre and post intervention CBFv, dynamic cerebral autoregulation (dCA) and cerebrovascular reactivity (CVRCO2). Conduit endothelial function, microvascular function and cardiorespiratory fitness were also assessed. Cardiorespiratory fitness improved (2.91 ml.min.kg(-1), 95%CI 0.49, 5.3; P = 0.02), regardless of exercise setting. Neither intervention had an impact on CBFv, CVRCO2, FMD or microvascular function (P > 0.05). There was a significant interaction between time and condition for dCA normalised gain with evidence of a decrease by 0.192%cm.s(-1).%mmHg(-1) (95%CI -0.318, -0.065) following training in the cold and increase (0.129%cm.s(-1).% mmHg(-1), 95%CI 0.011, 0.248) following training in the thermoneutral environment (P = 0.001). This was also evident for dCA phase with evidence of an increase by 0.072 rad (95%CI -0.007, 0.152) following training in the cold and decrease by 0.065 (95%CI -0.144, 0.014) radians following training in the thermoneutral environment (P = 0.02). Both training interventions improved fitness but CBFv, CVRCO2 and peripheral endothelial function were unaltered. Exercise training in the cold improved dCA whereas thermoneutral negated dCA.

The most common non-pharmacological intervention for both peripheral and cerebral vascular health is regular physical activity (e.g., exercise training), which improves function across a range of exercise intensities and modalities. Numerous non-exercising approaches have also been suggested to improved vascular function, including repeated ischemic preconditioning (IPC); heat therapy such as hot water bathing and sauna; and pneumatic compression. Chronic adaptive responses have been observed across a number of these approaches, yet the precise mechanisms that underlie these effects in humans are not fully understood. Acute increases in blood flow and circulating signalling factors that induce responses in endothelial function are likely to be key moderators driving these adaptations. While the impact on circulating factors and environmental mechanisms for adaptation may vary between approaches, in essence, they all centre around acutely elevating blood flow throughout the circulation and stimulating improved endothelium-dependent vascular function and ultimately vascular health. Here, we review our current understanding of the mechanisms driving endothelial adaptation to repeated exposure to elevated blood flow, and the interplay between this response and changes in circulating factors. In addition, we will consider the limitations in our current knowledge base and how these may be best addressed through the selection of more physiologically relevant experimental models and research. Ultimately, improving our understanding of the unique impact that non-pharmacological interventions have on the vasculature will allow us to develop superior strategies to tackle declining vascular function across the lifespan, prevent avoidable vascular-related disease, and alleviate dependency on drug-based interventions.

ABSTRACT Purpose The muscle perfusion response to postexercise cold-water immersion (CWI) is not well understood. We examined the effects of graded postexercise CWI upon global and regional quadriceps femoris muscle perfusion using positron emission tomography and [15O]H2O. Methods Using a matched-group design, 30 healthy men performed cycle ergometer exercise at 70% V̇O2peak to a core body temperature of 38°C, followed by either 10 min of CWI at 8°C, 22°C, or seated rest (control). Quadriceps muscle perfusion; thigh and calf cutaneous vascular conductance; intestinal, muscle, and local skin temperatures; thermal comfort; mean arterial pressure; and heart rate were assessed at preexercise, postexercise, and after CWI. Results Global quadriceps perfusion was reduced beyond the predefined minimal clinically relevant threshold (0.75 mL per 100 g·min−1) in 22°C water versus control (difference (95% confidence interval (CI)), −2.5 (−3.9 to −1.1) mL per 100 g·min−1). Clinically relevant decreases in muscle perfusion were observed in the rectus femoris (−2.0 (−3.0 to −1.0) mL per 100 g·min−1) and vastus lateralis (−3.5 (−4.9 to −2.0) mL per 100 g·min−1) in 8°C water, and in the vastus lateralis (−3.3 (−4.8 to −1.9) mL per 100 g·min−1) in 22°C water versus control. The mean effects for vastus intermedius and vastus medialis perfusion were not clinically relevant. Clinically relevant decreases in thigh and calf cutaneous vascular conductance were observed in both cooling conditions. Conclusions The present findings revealed that less noxious CWI (22°C) promoted clinically relevant postexercise decreases in global quadriceps muscle perfusion, whereas noxious cooling (8°C) elicited no effect.

[This corrects the article DOI: 10.3389/fphys.2020.609935.].

Background Chicken meat extract is a popular functional food in Asia. It is rich in the bioactive compounds carnosine and anserine, two histidine-containing dipeptides (HCD). Studies suggest that acute pre-exercise ingestion of chicken extracts has important applications towards exercise performance and fatigue control, but the evidence is equivocal. This study aimed to evaluate the ergogenic potential of the pre-exercise ingestion of a homemade chicken broth (CB) vs a placebo soup on a short-lasting, high-intensity cycling exercise. Methods Fourteen men participated in this double-blind, placebo-controlled, crossover intervention study. Subjects ingested either CB, thereby receiving 46.4 mg/kg body weight of HCD, or a placebo soup (similar in taste without HCD) 40min before an 8min cycling time trial (TT) was performed. Venous blood samples were collected at arrival (fasted), before exercise and at 5min recovery. Plasma HCD were measured with UPLC-MS/MS and glutathione (in red blood cells) was measured through HPLC. Capillary blood samples were collected at different timepoints before and after exercise. Results A significant improvement (p=0.033; 5.2%) of the 8min TT mean power was observed after CB supplementation compared to placebo. Post-exercise plasma carnosine (p<0.05) and anserine (p<0.001) was significantly increased after CB supplementation and not following placebo. No significant effect of CB supplementation was observed either on blood glutathione levels, nor on capillary blood analysis. Conclusions Oral CB supplementation improved the 8min TT performance albeit it did not affect the acid-base balance or oxidative status parameters. Further research should unravel the potential role and mechanisms of HCD, present in CB, in this ergogenic approach.

Sex differences in cerebrovascular disease rates indicate a possible role for ovarian sex steroid hormones in cerebrovascular function. To synthesise and identify knowledge gaps, a systematic review and meta-analysis was conducted to assess how ovarian sex steroid hormone changes across the lifespan affect cerebrovascular function in women. Three databases (EMBASE, MEDLINE and Web of Science) were systematically searched for studies on adult cerebrovascular function and ovarian sex steroid hormones. Forty-five studies met pre-defined inclusion criteria. Studied hormone groups included hormone replacement therapy (HRT; n = 17), pregnancy ( n = 12), menstrual cycle ( n = 7), menopause ( n = 5), oral contraception ( n = 2), and ovarian hyperstimulation ( n = 2). Outcome measures included pulsatility index (PI), cerebral blood flow/velocity (CBF), resistance index (RI), cerebral autoregulation, and cerebrovascular reactivity. Meta-analysis was carried out on HRT studies. PI significantly decreased [−0.05, 95% CI: (−0.10, −0.01); p = 0.01] in post-menopausal women undergoing HRT compared to post-menopausal women who were not, though there was considerable heterogeneity ( I 2 = 96.8%). No effects of HRT were seen in CBF ( p = 0.24) or RI ( p = 0.77). This review indicates that HRT improves PI in post-menopausal women. However, there remains insufficient evidence to determine how changing ovarian sex steroid hormone levels affects cerebrovascular function in women during other hormonal phases (e.g., pregnancy, oral contraception).

OBJECTIVES:For the effective treatment of childhood obesity, intervention attendance and behaviour change at home are both important. The purpose of this study was to qualitatively explore influences on attendance and behaviour change during a family-based intervention to treat childhood obesity in the North West of England (Getting Our Active Lifestyles Started (GOALS)).DESIGN:Focus groups with children and parents/carers as part of a broader mixed-methods evaluation.METHODS:Eighteen focus groups were conducted with children (n = 39, 19 boys) and parents/carers (n = 34, 5 male) to explore their experiences of GOALS after 6 weeks of attendance (/18 weeks). Data were analysed thematically to identify influences on attendance and behaviour change.RESULTS:Initial attendance came about through targeted referral (from health care professionals and letters in school) and was influenced by motivations for a brighter future. Once at GOALS, it was the fun, non-judgemental healthy lifestyle approach that encouraged continued attendance. Factors that facilitated behaviour change included participatory learning as a family, being accountable and gradual realistic goal setting, whilst challenges focussed on fears about the intervention ending and a lack of support from non-attending significant others.CONCLUSIONS:Factors that influence attendance and behaviour change are distinct and may be important at different stages of the family's change process. Practitioners are encouraged to tailor strategies to support both attendance and behaviour change, with a focus on whole family participation within and outside the intervention.

In this study, we examined whether the decrease in endothelial function associated with short-term exposure to elevated retrograde shear rate (SR), could be prevented when combined with a concurrent drop in transmural pressure in humans. Twenty-five healthy individuals reported to our laboratory on three occasions to complete 30-min experimental conditions, preceded and followed by assessment of endothelial function using flow-mediated dilation (FMD). We used cuff inflation for 30-min to manipulate retrograde SR and transmural pressure in the brachial artery. Subjects underwent, in randomised order: (1) forearm cuff inflation to 60 mmHg (distal cuff; causing increase in retrograde SR), (2) upper arm cuff inflation to 60 mmHg (proximal cuff; causing increase in retrograde SR + decrease in transmural pressure), and (3) no cuff inflation (Control). The distal and proximal cuff conditions both increased brachial artery retrograde SR (p < 0.001) and oscillatory shear index (p < 0.001). The Control intervention did not alter SR patterns or FMD (p > 0.05). A significant interaction-effect was found for FMD (p < 0.05), with the decrease during distal cuff (from 6.9 ± 2.3% to 6.1 ± 2.5%), being reversed to an increase with proximal cuff (from 6.3 ± 2.0 to 6.9 ± 2.0%). The proximal cuff-related increase in FMD could not be explained by the decrease in antegrade or increase in retrograde shear. This study suggests that a decrease in transmural pressure may ameliorate the decline in endothelial function that occurs following exposure to elevated retrograde shear in healthy individuals.

ABSTRACTIntroduction: Both ischaemic preconditioning (IPC) and muscle heat maintenance can be effective in enhancing repeated‐sprint performance (RSA) when applied individually, acting mechanisms of these interventions, however, likely differ. It is unclear if, when combined, these interventions could further improve RSA. Methods: Eleven trained cyclists undertook experimental test sessions, whereby IPC (4 × 5‐min at 220 mmHg) and SHAM (4 × 5‐min at 20 mmHg) were each performed on two separate visits, each combined with either passive muscle heating or thermoneutral insulation prior to an “all‐out” repeated‐sprint task (10 × 6‐s sprints with 24‐s recovery). Primary outcome measures were peak and average power output (W), whist secondary measures were muscular activation and muscular oxygenation, measured via Electromyography (EMG) and Near‐infrared spectroscopy (NIRS), respectively. Results: IPC did not enhance peak [6 (−14–26)W; P = 0.62] or average [12 (−7–31)W; P = 0.28] power output versus SHAM. Additionally, no performance benefits were observed when increasing muscle temperature in combination with IPC [5 (−14–19) watts; P = 0.67], or in isolation to IPC [9 (−9–28)W; P = 0.4] versus SHAM. No changes in EMG or microvascular changes were present (P > 0.05, respectively) between conditions. Conclusion: Overall, neither IPC, muscle heating, or a combination of both enhances RSA cycling performance in trained individuals.

Abstract In this study, we aimed to determine the exercise intensities eliciting the highest (FATmax) and the lowest (FATmin) fat oxidation rate in male cyclists and to compare these intensities with their individual aerobic (AeT) and anaerobic (AnT) thresholds, respectively. Twenty-two moderately trained male cyclists performed a 2-min stage graded exercise test until exhaustion using breath-by-breath gas analysis to determine maximal oxygen consumption (VO2max). The fat oxidation rate was calculated using a stoichiometric equation, with metabolic thresholds being determined by ventilatory gas analysis. In the present group of subjects, FATmax was found at a 21.34 ± 3.64 ml·kg−1·min−1 corresponding to 45.05 ± 7.68% VO2max. AeT occurred at an exercise intensity of 22.15 ± 4.84 ml·kg−1·min−1, matching 46.76 ± 10.24% VO2max. AnT and FATmin were located at intensities equivalent to 32.56 ± 5.52 ml·kg−1·min−1 and 32.30 ± 5.35 ml·kg−1·min−1 which corresponded to 68.74 ± 11.65 and 68.19 ± 11.29% VO2max, respectively. The correlation between FATmax and AeT was strong (r = 0.80, p < 0.05). No statistical difference was observed between FATmin and AnT (r = 0.99, p < 0.05). The strong relationship between observed indices can be used to provide a more tailored exercise approach.

Objective: To assess the efficacy of heat thermotherapy to improve cardiovascular and cardiometabolic health, and to compare potential heat thermotherapy moderating factors. Design: Systematic review and narrative synthesis. Data Sources: Electronic databases (MEDLINE, EMBASE and Web of Science) were searched up to 6th February 2020. Eligibility criteria for selecting studies: Journal articles with adult participants, a controlled trial study design, and a passive heating stimulus with a cardiovascular or cardiometabolic health outcome were included. Results: From 1036 articles, 39 articles met the inclusion criteria. Heat thermotherapy was delivered acutely (one bout; n=19), short term (2-15 bouts; n=6) and chronically (>15 bouts; n=14), via either hot water immersion (n=26; water temperature 38-43 °C) or heated air exposure (n=11; air temperature 31-90 °C), or water perfused suit/handheld device (n=2). Heat exposure ranged from 10 to 240 minutes. Cardiovascular and cardiometabolic measurement techniques varied across studies, alongside participant age (≤35 years, n=376; >35 ≤60 years, n=335 and >60 years, n=350) and health status. 21/27 studies measuring cardiovascular outcomes reported positive health benefits, including increased flow-mediated dilation (1.3-5.3%) and lower systolic blood pressure (4-16 mm Hg). 15/22 studies measuring cardiometabolic outcomes reported positive health benefits, including reduced postprandial glucose (-0.89 to -0.5 mmol.L -1) and C-reactive protein concentrations (-0.9 to -10.94 mg.L-1). Conclusion: Overall, 29/39 studies demonstrated significant positive cardiovascular or cardiometabolic health benefits from heat thermotherapy across various population demographics, despite varied study design and modality. Heat thermotherapy is an efficacious treatment for cardiovascular disease alongside pharmaceutical and exercise-based interventions.

Using positron emission tomography, we report for the first time muscle perfusion heterogeneity in the quadriceps femoris in response to different degrees of cold-water immersion (CWI). Noxious CWI temperatures (8°C) increase perfusion in the deep quadriceps muscle, whereas superficial quadriceps muscle perfusion is reduced in cooler (15°C) water. Therefore, these data have important implications for the selection of CWI approaches used in the treatment of soft tissue injury, while also increasing our understanding of the potential mechanisms underpinning CWI.

Several techniques exist for the determination of skin blood flow that have historically been used in the investigation of thermoregulatory control of skin blood flow, and more recently, in clinical assessments or as an index of global vascular function. Skin blood flow measurement techniques differ in their methodology and their strengths and limitations. To examine the historical development of techniques for assessing skin blood flow by describing the origin, basic principles, and important aspects of each procedure and to provide recommendations for best practise. Venous occlusion plethysmography was one of the earliest techniques to intermittently index a limb's skin blood flow under conditions in which local muscle blood flow does not change. The introduction of laser Doppler flowmetry provided a method that continuously records an index of skin blood flow (red cell flux) (albeit from a relatively small skin area) that requires normalisation due to high site-to-site variability. The subsequent development of laser Doppler and laser speckle imaging techniques allows the mapping of skin blood flow from larger surface areas and the visualisation of capillary filling from the dermal plexus in two dimensions. The use of iontophoresis or intradermal microdialysis in conjunction with laser Doppler methods allows for the local delivery of pharmacological agents to interrogate the local and neural control of skin blood flow. The recent development of optical coherence tomography promises further advances in assessment of the skin circulation via three-dimensional imaging of the skin microvasculature for quantification of vessel diameter and vessel recruitment.

Background Premenopausal women have a lower incidence of cardiovascular disease, which may partly be due to a protective effect of estrogen on endothelial function. Animal studies suggest that estrogen may also improve the relationship between shear rate ( SR ) and endothelial function. We aimed to explore the relationship between endothelial function (ie, flow‐mediated dilation [ FMD ]) and SR (ie, SR area under the curve [ SRAUC ]) in women versus men, and between pre‐ versus postmenopausal women. Methods and Results Brachial artery FMD and SRAUC were measured in accordance with expert‐consensus guidelines in 932 healthy participants who were stratified into young adults (18‐40 years, 389 men, 144 women) and older adults (>40 years, 260 men, 139 women). Second, we compared premenopausal (n=173) and postmenopausal women (n=110). There was evidence of a weak correlation between SRAUC and FMD in all groups but older men, although there was variation in strength of outcomes. Further exploration using interaction terms (age‐sex× SRAUC ) in linear regression revealed differential relationships with FMD (young women versus young men [β=−5.8 −4 , P =0.017] and older women [β=−5.9 −4 , P =0.049]). The correlation between SRAUC and FMD in premenopausal women ( r 2 =0.097) was not statistically different from that in postmenopausal women ( r 2 =0.025; Fisher P =0.30). Subgroup analysis using stringent inclusion criteria for health markers (n=505) confirmed a stronger FMD ‐ SRAUC correlation in young women compared with young men and older women. Conclusions Evidence for a stronger relationship between endothelial function and the eliciting SR stimulus is present in young women compared with men. Estrogen may contribute to this finding, but larger healthy cohorts are required for conclusive outcomes.

Ischemic preconditioning (IPC) is an intervention whereby brief intermittent ischemic episodes are induced in a limb (usually 3 or 4×5-minute arterial occlusion bouts, interspersed with 5 minutes of reperfusion) either at the site of interest (IPC) or at a distance from the site of interest (remote ischemic preconditioning, RIPC). This phenomenon has been used as a clinical tool in order to enhance a tissues tolerance to ischemia-induced injury. Over the last 7 years, a plethora of research studies (~40 studies) have aimed to determine the impact of IPC performed on the limb administered prior to exercise, to examine the impact on exercise performance. This was driven by the remarkable performance improvements observed in the first research studies around IPC and exercise benefits. A systematic review reinforced the presence of beneficial responses on performance when exercise was preceded by IPC, with largest improvements observed during aerobic exercise. More recently, practitioners and researchers have posed questions such as “why does it work?” and “how should this be optimally used to help an athlete?” These questions are critical in dictating if, how, and when IPC should be used in an elite athlete setting, with the sole aim of enhancing athletic performance in sports and exercise. This chapter will firstly outline the potential benefits of IPC on exercise performance. Specifically, we will identify which athletes may benefit the most from this stimulus by discussing potential moderating factors that influence the impact of IPC on exercise performance. Secondly, potential underlying mechanisms explaining the benefits of IPC on exercise performance will be discussed. Finally, we will provide recommendations for both the general population and athletes, based upon the current research findings, on the how and when to administer IPC for optimal performance benefits.

PURPOSE: This study examined changes in anthropometric and cardiorespiratory fitness (CRF) characteristics of 26,325 Grade 6 (G6) schoolboys (11.0 -12.99 y) living in the State of Qatar between 2003-2016. METHODS: Anthropometric measures included standing height (cm), body mass (kg) and body mass index (BMI, kg/m2). A multistage shuttle run test (MSRT, laps) was used to assesses CRF. Comparisons between Qatari and non-Qatari boys were also conducted. RESULTS: The results showed a trend for decreasing CRF (less MSRT laps) and increasing fatness (higher BMI) across the study period, irrespective of nationality. Qatari students generally performed worse on the MSRT test and were fatter than their non-Qatari peers. Also, the Qatari students displayed bigger decreases in MSRT (10 vs 4 laps) and their body mass (2.5 vs 0.7 kg) and BMI (1.3 vs 0.6 kg/m2) increased more over the study period than their non-Qatari peers. Furthermore, the percentage of G6 schoolboys classified as overweight or obese increased over the study period for all nationalities, with Qatari boys showing a greater prevalence of overweight or obesity than their non-Qatari peers. For example, the percentage of Qatari boys classified as overweight or obese by Centers for Disease Control and Prevention (CDC) standards increased from an average of 40.1% between 2003-2006 to 49.3% between 2013-2016 while the average for non-Qatari boys increased from 32.6% to 39.9% for the same periods. CONCLUSIONS: These data support the need to establish a mechanism for the prevention and treatment of obesity and the development of physical activity strategies in the State of Qatar.

Type 2 diabetes mellitus (T2DM) and obesity are syndemic and will have a significant impact on affected individuals and healthcare services worldwide. Evidence shows that T2DM remission can be achieved with significant weight loss in those who are younger with early diabetes and requiring fewer medications for glycaemic control. DIADEM-I aims to examine the impact of an intensive lifestyle intervention (ILI) using a low-energy diet (LED) meal replacement approach combined with physical activity in younger individuals with early T2DM.