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Background Sedentary behavior (SB) is associated with increased risks of detrimental health outcomes. Few studies have explored correlates of SB in physically active individuals. Furthermore, SB correlates may depend on settings of SB, such as occupation, transportation and leisure time sitting. This study aims to identify subject-, lifestyle- and health-related correlates for total SB and different SB domains: transportation, occupation, and leisure time. Methods Dutch participants were recruited between June, 2015 and December, 2016. Participant characteristics (i.e. age, sex, weight, height, marital status, education level, employment), lifestyle (sleep, smoking, alcohol consumption, physical activity) and medical history were collected via an online questionnaire. SB was assessed using the Sedentary Behavior Questionnaire and estimated for 9 different activities during weekdays and weekend days. Logistic regression was used to calculate odds ratios and 95% confidence intervals for the association between correlates and SB. Total SB was dichotomized at > 8 h/day and > 10 h/day, and being sedentary during transportation, occupation and leisure time at the 75th percentile (60 min/day, 275 min/day and 410 min/day, respectively). Results In total, 8471 participants (median age 55, 55% men) were included of whom 86% met the physical activity guidelines. Median SB was 9.1 h/day (Q25 6.3-Q75 12.0) during weekdays and 7.4 h/day (Q25 5.5-Q75 9.5) during weekend days. SB was most prevalent during leisure time (5.3 h/day; Q25 3.9-Q75 6.8), followed by occupation (2 h/day; Q25 0.1-Q75 4.6) and transportation (0.5 h/day; Q25 0.2-Q75 1.0). Younger age, male sex, being unmarried, higher education, employment and higher BMI were significantly related to higher levels of total SB. Younger age, male sex, employment, and higher BMI increased the odds for high SB volumes during occupation and transportation. Higher education, being unmarried and smoking status were positively associated with high volumes of occupational SB only, whereas older age, being unmarried, unemployment, higher BMI and poor health were positively linked to leisure time SB. Conclusions SB is highly prevalent in physically active individuals, with SB during leisure time as the most important contributor. Correlates for high volumes of SB vary substantially across SB domains, emphasizing the difficulty to target this unhealthy lifestyle.

Background: Assessment of endothelial function using brachial artery flow-mediated dilation (FMD) predicts future cardiovascular disease (CVD) risk. However, poor adherence to protocol guidelines and lack of reference values hinders widespread FMD use. This study established age- and sex-specific reference intervals for brachial artery FMD in healthy individuals and examined the relation with CVD risk factors. Methods: Collected according to expert-consensus guidelines, we combined brachial artery FMD and subject characteristics/medical history from 5,362 individuals (4–84 years; 2,076 females). We first examined healthy individuals (n = 1,403 [582 females]) to generate age-/sex-specific percentile curves. Subsequently, we included subjects with CVD risk factors but without disease (un-medicated n = 3,167 [1,247 females], and medicated n = 792 [247 females]). Multiple linear regression tested the relation of CVD risk factors with FMD. Results: Healthy men showed a negative, curvilinear relation between FMD and age, whilst females revealed a linear relation that started higher, but declined at a faster rate. Age-/sex-related differences in FMD, at least partly, relate to baseline artery diameter. FMD was affected by CVD risk factors in un-medicated (e.g. systolic-/diastolic blood pressure, diabetes) and medicated subjects (e.g. dyslipidaemia). Importantly, sex mediated these effects (p < 0.05), with (supra) normalisation of FMD in medicated men, but not in women (except for blood pressure). Conclusion: Sex alters the age-related decline in FMD, which is partly explained through differences in artery diameter. Sex also altered the effect of some CVD risk factors and medication on FMD. This work improves interpretation and future use of the FMD technique when strictly adhering to FMD protocol guidelines.

Background: Sympathetic stimulation in central arteries, such as the carotid artery, lead to vasodilation in healthy subjects and vasoconstriction in those with cardiovascular disease. Moreover, this response has independent prognostic value for future events. Whether the aorta demonstrates similar responsiveness is unknown. This is relevant, since this may help to better predict outcomes and progression in abdominal aortic aneurysm (AAA). Objective: The aim of this explorative study is to investigate the correlation between the magnitude of the abdominal aorta and the carotid artery diameter and blood flow responses during the sympathetic stimulation (using the Cold Pressor Test (CPT)) between healthy young, healthy older and individuals with AAA. Method: In this explorative study 60 subjects will be included divided into a healthy young group, healthy older group and an AAA group. All subjects will undergo the CPT, while using duplex ultrasound to simultaneously examine the diameter and blood velocity of the abdominal aorta and carotid artery. Results: We aim to present our first results of the correlation between the abdominal aorta and carotid artery parameters at the conference. Conclusion: When confirming a correlation between the magnitude of the abdominal aorta and the carotid artery diameter during the CPT, assessment of carotid artery reactivity to CPT may represent a simple, surrogate measure of central (i.e. aorta) endothelial function. This may help in predicting AAA progression and improve decision-making for treatment.

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Contains fulltext : 229875.pdf (Publisher’s version ) (Open Access) Whilst both cardiac output (CO) and total peripheral resistance (TPR) determine mean arterial blood pressure (MAP), their relative importance in the pressor response to isometric exercise remains unclear. This study aimed to elucidate the relative importance of these two different factors by examining pressor responses during cardiopulmonary unloading leading to step-wise reductions in CO. Hemodynamics were investigated in 11 healthy individuals before, during and after two-minute isometric exercise during lower body negative pressure (LBNP; -20mmHg and -40mmHg). The blood pressure response to isometric exercise was similar during normal and reduced preload, despite a step-wise reduction in CO during LBNP (-20mmHg and -40mmHg). During -20mmHg LBNP, the decreased stroke volume, and consequently CO, was counteracted by an increased TPR, while heart rate (HR) was unaffected. HR was increased during -40 mmHg LBNP, although insufficient to maintain CO; the drop in CO was perfectly compensated by an increased TPR to maintain MAP. Likewise, transient application of LBNP (-20mmHg and -40mmHg) resulted in a short transient drop in MAP, caused by a decrease in CO, which was compensated by an increase in TPR. This study suggests that, in case of reductions of CO, changes in TPR are primarily responsible for maintaining the pressor response during isometric exercise. This highlights the relative importance of TPR compared to CO in mediating the pressor response during isometric exercise.

BACKGROUND The mechanisms underlying the effect of preconditioning on remote microvasculature remains undisclosed. The primary objective was to document the remote effect of ischemic preconditioning on microvascular function in humans. The secondary objective was to test if exercise also induces remote microvascular effects. METHODS AND RESULTS A total of 12 healthy young men and women participated in 2 experimental days in a random counterbalanced order. On one day the participants underwent 4×5 minutes of forearm ischemic preconditioning, and on the other day they completed 4×5 minutes of hand‐grip exercise. On both days, catheters were placed in the brachial and femoral artery and vein for infusion of acetylcholine, sodium nitroprusside, and epoprostenol. Vascular conductance was calculated from blood flow measurements with ultrasound Doppler and arterial and venous blood pressures. Ischemic preconditioning enhanced ( P P P CONCLUSIONS These findings demonstrate that ischemic preconditioning of the forearm improves remote microvascular endothelial function and suggest that one of the underlying mechanisms is a humoral‐mediated potentiation of prostacyclin formation.

The aim of this study was to assess the effect of exercise intensity on the thermal sensory function of active and inactive limbs. In a randomised and counterbalanced manner, 13 healthy young male participants (25 &plusmn, 6 years, 1.8 &plusmn, 0.1 m, 77 &plusmn, 6 kg) conducted: (1) 30-min low-intensity (50% heart rate maximum, HRmax, LOW) and (2) 30-min high-intensity (80% HRmax, HIGH) cycling exercises, and (3) 30 min of seated rest (CONTROL). Before, immediately after, and 1 h after, each intervention, thermal sensory functions of the non-dominant dorsal forearm and posterior calf were examined by increasing local skin temperature (1 &deg, C/s) to assess perceptual heat sensitivity and pain thresholds. Relative to pre-exercise, forearm heat sensitivity thresholds were increased immediately and 1 hr after HIGH, but there were no changes after LOW exercise or during CONTROL (main effect of trial, p = 0.017). Relative to pre-exercise, calf heat sensitivity thresholds were not changed after LOW or HIGH exercise or during CONTROL (main effect of trial, p = 0.629). There were no changes in calf (main effect of trial, p = 0.528) or forearm (main effect of trial, p = 0.088) heat pain thresholds after exercise in either LOW or HIGH or CONTROL. These results suggest that cutaneous thermal sensitivity function of an inactive limb is only reduced after higher intensity exercise but is not changed in a previously active limb after exercise. Exercise does not affect heat pain sensitivity in either active or inactive limbs.

BACKGROUND: Acute exercise leads to an immediate drop in blood pressure (BP), also called post-exercise hypotension (PEH). Exercise in hypoxia is related to additional vasodilation, potentially contributing to more profound PEH. Therefore, we investigated the impact of hypoxia versus normoxia on the magnitude of PEH. Second, we examined whether these changes in PEH relate to the BP-lowering effects of 12-week exercise training under hypoxia. METHODS: In this prospective study, 21 healthy individuals (age 22.2 ±â€Š3.0 years, 14 male) performed a 45-minute high-intensity running exercise on 2 different days in a random order, under hypoxia (fraction of inspired oxygen 14.5%) and normoxia (fraction of inspired oxygen 20.9%). BP was examined pre-exercise (t = 0) and at t = 15, t = 30, t = 45, and t = 60 minutes post-exercise. Afterward, subjects took part in a 12-week hypoxic running exercise training program. Resting BP was measured before and after the 12-week training program. RESULTS: Acute exercise induced a significant decrease in systolic BP (systolic blood pressure [SBP], P = .001), but not in diastolic BP (diastolic blood pressure [DBP], P = .113). No significant differences were observed in post-exercise BP between hypoxic and normoxic conditions (SBP, P = .324 and DBP, P = .204). Post-exercise changes in SBP, DBP, and mean arterial pressure significantly correlated to the 12-week exercise training-induced changes in SBP (r = 0.557, P = .001), DBP (r = 0.615, P 

Contains fulltext : 219274.pdf (Publisher’s version ) (Closed access) Chronic changes in left ventricular (LV) hemodynamics, such as those induced by increased afterload (i.e., hypertension), mediate changes in LV function. This study examined the proof of concept that 1) the LV longitudinal strain (epsilon)-volume loop is sensitive to detecting an acute increase in afterload, and 2) these effects differ between healthy young versus older men. Thirty-five healthy male volunteers were recruited, including 19 young (24 +/- 2 yr) and 16 older participants (67 +/- 5 yr). Tests were performed before, during, and after 10-min recovery from acute manipulation of afterload. Real-time hemodynamic data were obtained and LV longitudinal epsilon-volume loops were calculated from four-chamber images using two-dimensional echocardiography. Inflation of the anti-gravity (anti-G) suit resulted in an immediate increase in heart rate, blood pressure, and systemic vascular resistance and a decrease in stroke volume (all P < 0.05). This was accompanied by a decrease in LV peak epsilon, slower slope of the epsilon-volume relationship during early diastole, and an increase in uncoupling (i.e., compared with systole; little change in epsilon per volume decline during early diastole and large changes in epsilon per volume decline during late diastole) (all P < 0.05). All values returned to baseline levels after recovery (all P > 0.05). Manipulation of cardiac hemodynamics caused comparable effects in young versus older men (all P > 0.05). Acute increases in afterload immediately change the diastolic phase of the LV longitudinal epsilon-volume loop in young and older men. This supports the potency of the LV longitudinal epsilon-volume loop to provide novel insights into dynamic cardiac function in humans in vivo.

Low-cost workplace interventions are required to reduce prolonged sitting in office workers as this may improve employees&rsquo, health and well-being. This study aimed to assess the acceptability and feasibility of an e-health intervention to reduce prolonged sitting among sedentary UK-based office workers. Secondary aims were to describe preliminary changes in employee health, mood and work productivity after using an e-health intervention. Healthy, university office workers (n = 14) completed this study. An 8 week randomised crossover design was used, consisting of two trials: Intervention (computer-based prompts) and Control. Eligibility and retention rates were recorded to assess the feasibility of the trial and interviews were conducted following the intervention to explore its acceptability. Sitting, standing and stepping were objectively assessed prior to and during week 8 of each trial. Before and after each trial, measurements of vascular function, cerebrovascular function, mood and work productivity were obtained. This study had eligibility and retention rates of 54.5% and 77.8%, respectively. Participants expressed a lack of autonomy and disruption to their workflow when using the e-health intervention, raising concerns over its acceptability and long-term implementation. Preliminary data indicate that the intervention may improve the patterning of activity accrued during work hours, with increases in the number of standing and stepping bouts completed, in addition to improving vascular function. This e-health intervention is feasible to deliver in a cohort of university office workers. However, adaptations to its implementation, such as personalised settings, are needed to increase acceptability before larger trials can be conducted.

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.

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Exposure to extreme cold environments is potentially life‐threatening. However, the world record holder of full‐body ice immersion has repeatedly demonstrated an extraordinary tolerance to extreme cold. We aimed to explore thermoregulatory, metabolic, and cardiovascular responses during 88 min of full‐body ice immersion. We continuously measured gastrointestinal temperature (Tgi), skin temperature (Tskin), blood pressure, and heart rate (HR). Oxygen consumption (VO2) was measured at rest, and after 45 and 88 min of ice immersion, in order to calculate the metabolic heat production. Tskin dropped significantly (28–34°C to 4–15°C) and VO2 doubled (5.7–11.3 ml kg−1 min−1), whereas Tgi (37.6°C), HR (72 bpm), and mean arterial pressure (106 mmHg) remained stable during the first 30 min of cold exposure. During the remaining of the trial, Tskin and VO2 remained stable, while Tgi gradually declined to 37.0°C and HR and mean arterial blood pressure increased to maximum values of 101 bpm and 115 mmHg, respectively. Metabolic heat production in rest was 169 W and increased to 321 W and 314 W after 45 and 80 min of ice immersion. Eighty‐eight minutes of full‐body ice immersion resulted in minor changes of Tgi and cardiovascular responses, while Tskin and VO2 changed markedly. These findings may suggest that our participant can optimize his thermoregulatory, metabolic, and cardiovascular responses to challenge extreme cold exposure., We investigated the thermoregulatory, metabolic, and cardiovascular responses of the world record holder of full‐body ice immersion when exposed to 88 min of ice immersion. Ice immersion resulted in minor changes of Tgi and cardiovascular responses, while Tskin and VO2 changed markedly.

Background: Polyphenol-rich dietary sources are acknowledged to have potential cardiovascular health benefits, particularly in reducing cardiovascular disease risk. Methods: This systematic review sought to determine the effect of polyphenol-rich foods and beverages upon microvascular function, which is of considerable importance in its contribution towards the pathophysiology of microvascular-related complications but also in the future development of (macro-vessel) cardiovascular disease. Results: Overall, consumption of polyphenol-rich foods and beverages demonstrate improved microvascular function, although this is dependent upon the polyphenol source, the dose of the product, the duration of consumption and the population group studied. Most subgroups reviewed suggest an overall beneficial effect on microvascular function, particularly grape-derived products, cocoa, tea, pine bark and Rutaceae aurantiae. Other groups remain equivocal and require further study due to the limited research performed to date. Conclusion: Polyphenols are abundant in the human diet and this systematic review demonstrates that they are an inexpensive, non-pharmacological approach for improving cardiovascular health in currently healthy individuals and in populations with microvascular dysfunction.

Item does not contain fulltext PURPOSE: To examine the clinical impact of cardiorespiratory fitness (CRF) and improvements in CRF after cardiac rehabilitation (CR) in heart failure (HF) patients for their risk of all-cause mortality and unplanned hospitalization. Secondly, to investigate possible factors associated with the absence of improvement in CRF after rehabilitation. METHODS: We included 155 HF patients receiving CR between October 2009 and January 2015. Patients performed an incremental bicycle test to assess CRF through peak oxygen uptake (VO2-peak) before and after CR-based supervised exercise training. Patients were classified as responders or non-responders based on pre-to-post CR changes in VO2-peak (>/=6% and

Decreased cerebrovascular blood flow and function are associated with lower cognitive functioning and increased risk of neurodegenerative diseases. Prolonged sitting impairs peripheral blood flow and function, but its effects on the cerebrovasculature are unknown. This study explored the effect of uninterrupted sitting and breaking up sitting time on cerebrovascular blood flow and function of healthy desk workers. Fifteen participants (10 male, 35.8 ± 10.2 yr, body mass index: 25.5 ± 3.2 kg/m2) completed, on separate days, three 4-h conditions in a randomized order: 1) uninterrupted sitting (SIT), 2) sitting with 2-min light-intensity walking breaks every 30 min (2WALK), or 3) sitting with 8-min light-intensity walking breaks every 2 h (8WALK). At baseline and 4 h, middle cerebral artery blood flow velocity (MCAv) and CO2 reactivity (CVR) of the MCA and carotid artery were measured using transcranial Doppler (TCD) and duplex ultrasound, respectively. Cerebral autoregulation (CA) was assessed with TCD using a squat-stand protocol and analyzed to generate values of gain and phase in the very low, low, and high frequencies. There was a significant decline in SIT MCAv (−3.2 ± 1.2 cm/s) compared with 2WALK (0.6 ± 1.5 cm/s, P = 0.02) but not between SIT and 8WALK (−1.2 ± 1.0 cm/s, P = 0.14). For CA, the change in 2WALK very low frequency phase (4.47 ± 4.07 degrees) was significantly greater than SIT (−3.38 ± 2.82 degrees, P = 0.02). There was no significant change in MCA or carotid artery CVR ( P > 0.05). Results indicate that prolonged uninterrupted sitting in healthy desk workers reduces cerebral blood flow; however, this is offset when frequent short-duration walking breaks are incorporated. NEW & NOTEWORTHY Prolonged uninterrupted sitting in healthy desk workers reduces cerebral blood flow. However, this reduction in cerebral blood flow is offset when frequent short-duration walking breaks are incorporated into this sitting period. For those who engage in long periods of sedentary behavior, chronically breaking up these sitting periods with frequent active break strategies may have important implications for cerebrovascular health; however, further research should explore this hypothesis.

Contains fulltext : 187840.pdf (Publisher’s version ) (Closed access) BACKGROUND & AIMS: Black tea is a main source of flavonoids in the Western diet and has been associated with reduced risk for cardiovascular disease, possibly through lowering blood pressure. These effects may be mediated through improving endothelial function of resistance arteries. The aim of this study was therefore to examine the acute impact of black tea on forearm resistance artery endothelial function in healthy, normotensive middle-aged subjects. METHODS: Twenty middle-aged men and women (age-range 45-75 years) were recruited into a double-blind, randomized, placebo-controlled crossover intervention study. Forearm resistance artery blood flow (FBF, measured using venous occlusion plethysmography) in response to incremental doses of acetylcholine, sodium nitroprusside and L-N(G)-monomethyl arginine were determined 2 h after consumption of either black tea containing approximately 400 mg flavonoids (equivalent to 2-3 cups of tea) or a taste- and color-matched placebo. RESULTS: The mean FBF-response to acetylcholine after tea consumption was 23% higher compared to the response after placebo (95% CI: -20%, +88%), but this difference did not reach statistical significance (P = 0.32). No significant differences in the FBF-responses to sodium nitroprusside and L-N(G)-monomethyl arginine were found between the tea and placebo interventions (P = 0.96 and 0.74, respectively). Correcting FBF for changes in blood pressure did not alter the outcomes. CONCLUSIONS: We found no evidence that acute intake of black tea significantly altered endothelium-dependent vasodilation of forearm resistance arteries in healthy middle-aged subjects. Interventions with a longer duration of tea ingestion are required to further explore the (long-term) impact of tea flavonoids on blood pressure regulatory mechanisms. This trial was registered at clinicaltrials.gov as NCT02328339. 01 februari 2018

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Objective: To establish the prevalence of Periodic Limb Movements during Sleep (PLMS) in patients with tetraplegia, controlling for obstructive sleep apnea. To explore whether demographic and injury characteristics affect PLMS.\ud \ud Study Design: Retrospective cohorts.\ud \ud Setting and Participants: One hundred seventy-three participants with acute (12 months) tetraplegia who underwent full overnight diagnostic sleep studies.\ud \ud Interventions and outcome measures: Two hundred sixty-two sleep study recordings were included. A randomly selected subgroup of 21 studies was assessed for PLM during wakefulness. Data were analysed according to the current American Academy of Sleep Medicine guidelines.\ud \ud Results: Of the participants, 41.6% (43(15.7) years and 14.9% female) had a motor and sensory complete lesion. Sleep was poor with both OSA (87.8% with apnea hypopnoea index ≥ 5) and PLMS (58.4% with PLMS per hour PLMSI > 15) highly prevalent. There was no difference in the PLMSI between those with OSA (36.3(39.8)) or without (42.2(37.7), P = 0.42). PLMS were evident during REM and NREM sleep in all of the 153 patients with PLMSI > 15. All 21 participants in the subgroup of studies analysed for the PLM during quiet wakefulness, exhibited limb movements. None of the modelled variables (injury completeness, gender, OSA severity or time since injury) significantly predicted a PLMSI > 15 (P = 0.343).\ud \ud Conclusion: In conclusion, this study confirms the high prevalence of PLM in tetraplegia and the presence of leg movements in NREM and REM sleep along with wakefulness after controlling for OSA. No associations between the presence of PLMS and patient characteristics or injury specific aspects were found.

Objectives The purpose of this study was to examine left ventricular (LV) strain (ԑ)-volume loops to provide novel insight into the haemodynamic cardiac consequences of aortic valve stenosis (AS) and aortic valve regurgitation (AR). Methods 27 participants were retrospectively recruited: AR (n = 7), AS (n = 10) and controls (n = 10). Standard transthoracic echocardiography was utilised to obtain apical 4 chamber images to construct ԑ-volume relationships were assessed by: Early systolic ԑ (ԑ_ES), slope of ԑ-volume relation during systole (Sslope), End-systolic peak ԑ (peak ԑ), Diastolic uncoupling (systolic ԑ-diastolic ԑ at same volume) during early diastole (UNCOUP_ED) and late diastole (UNCOUP_LD). ROC-curves were used to determine the ability to detect impaired LV function. Results Whilst LV ejection fraction was comparable between groups, longitudinal peak ԑ was similarly reduced compared to controls. In contrast, ԑ_ES and Sslope were lower in both pathologies compared to controls (P 0.05) to distinguish AS vs Controls, AR vs Controls and AS vs AR, respectively. Conclusions Temporal changes in ԑ-volume characteristics provide novel insight into the haemodynamic cardiac impact of AS and AR. Contrary to traditional measures (i.e. ejection fraction, peak ԑ), these novel measures successfully distinguish between the haemodynamic cardiac impact of AS and AR. This article is protected by copyright. All rights reserved.

Item does not contain fulltext Ischemic preconditioning (IPC) may enhance exercise performance. Cardioprotective effects of IPC are known to re-occur 24h after the stimulus. Whether the delayed effect of IPC has similar effects as IPC on exercise performance is unknown. OBJECTIVES: Examine whether IPC applied 24h (24-IPC) before exercise is equally effective as IPC in improving exercise performance. DESIGN: Randomized, cross-over study METHODS: 12 healthy participants were randomly exposed to SHAM-session, IPC or 24-IPC before a self-paced 5km running trial on a treadmill. Subjects were blinded for time, speed and heart rate. Furthermore, heart rate, BORG, and the local tissue saturation index were measured during exercise, while lactate levels were determined after running. Using a regression model, we explored whether these parameters predicted the change in running time after IPC and 24-IPC. RESULTS: We found no differences in finish time after IPC (SHAM: 1400+/-105s, IPC: 1381+/-112s, 24-IPC: 1385+/-113s; p=0.30). However, we observed a significant positive relation between the change in finish time after IPC and 24-IPC (p=0.016; r=0.677). Using stepwise linear regression, a lower post-exercise blood lactate level after IPC or 24-IPC was significantly related to an improvement in finish time (R2=0.47, beta=-0.687, p=0.007). CONCLUSIONS: Although no significant effect of IPC or 24-IPC on exercise performance was found, individual finish time after IPC and 24-IPC were strongly correlated. Therefore, our data suggest that, at the individual level, the effects of 24-IPC are closely related to the effects of IPC. 01 februari 2017

Contains fulltext : 173074.pdf (Publisher’s version ) (Closed access) OBJECTIVES: Carotid artery reactivity (CAR%), involving carotid artery diameter responses to a cold pressor test (CPT), is a noninvasive measure of conduit artery function in humans. This study examined the impact of age and cardiovascular risk factors on the CAR% and the relationship between CAR% and coronary artery vasodilator responses to the CPT. METHODS: Ultrasound was used to measure resting and peak carotid artery diameters during the CPT, with CAR% being calculated as the relative change from baseline (%). We compared CAR% between young (n = 50, 24 +/- 3 years) and older participants (n = 44, 61 +/- 8 years), and subsequently assessed relationships between CAR% and traditional cardiovascular risk factors in 50 participants (44 +/- 21 years). Subsequently, we compared left anterior descending (LAD) artery velocity (using transthoracic Doppler) with carotid artery diameter (i.e. CAR%) during the CPT (n = 33, 37 +/- 17 years). RESULTS: A significantly larger CAR% was found in young versus older healthy participants (4.1 +/- 3.7 versus 1.8 +/- 2.6, P < 0.001). Participants without cardiovascular risk factors demonstrated a higher CAR% than those with at least two risk factors (2.9 +/- 2.9 versus 0.5 +/- 2.9, P = 0.019). Carotid artery diameter and LAD velocity increased during CPT (P < 0.001). Carotid diameter and change in velocity correlated with LAD velocity (r = 0.486 and 0.402, P < 0.004 and 0.02, respectively). CONCLUSION: Older age and cardiovascular risk factors are related to lower CAR%, while CAR% shows good correlation with coronary artery responses to the CPT. Therefore, CAR% may represent a valuable technique to assess cardiovascular risk, while CAR% seems to reflect coronary artery vasodilator function. 01 mei 2017

Supplying the brain with enough blood flow is essential to keep us alive and maintain our brain health. Reductions in brain blood flow can negatively affect the ability to think. Decreased blood flow to the brain can also lead to brain diseases, such as dementia, which is a condition that causes permanent memory loss and confusion. Scientists are beginning to think that sitting may be bad for brain blood flow. Understanding how sitting affects the brain is therefore very important. We conducted a study in which participants either sat down without any breaks for 4 h, or sat down but took a short walking break every 30 min, or took a longer walking break every 2 h. After sitting without any breaks, brain blood flow decreased. However, when participants took a walking break every 30 min that prevented the decrease in brain blood flow. These results suggest we should encourage people to take regular breaks from sitting to help maintain brain health.

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.

Increase in mean shear stress represents an important and potent hemodynamic stimulus to improve conduit artery endothelial function in humans. No previous study has examined whether fluctuations in shear rate patterns, without altering mean shear stress, impacts conduit artery endothelial function. This study examined the hypothesis that 30-min exposure to fluctuations in shear rate patterns, in the presence of unaltered mean shear rate, improves brachial artery flow-mediated dilation. Fifteen healthy men (27.3 ± 5.0 yr) completed the study. Bilateral brachial artery flow-mediated dilation was assessed before and after unilateral exposure to 30 min of intermittent negative pressure (10 s, −40mmHg; 7 s, 0 mmHg) to induce fluctuation in shear rate, while the contralateral arm was exposed to a resting period. Negative pressure significantly increased shear rate, followed by a decrease in shear rate upon pressure release (both P < 0.001). Across the 30-min intervention, mean shear rate was not different compared with baseline ( P = 0.458). A linear mixed model revealed a significant effect of time observed for flow-mediated dilation ( P = 0.029), with exploratory post hoc analysis showing an increase in the intervention arm (∆FMD +2.0%, P = 0.008), but not in the contralateral control arm (∆FMD +0.5%, P = 0.664). However, there was no effect for arm ( P = 0.619) or interaction effect ( P = 0.096). In conclusion, we found that fluctuations in shear patterns, with unaltered mean shear, improves brachial artery flow-mediated dilation. These novel data suggest that fluctuations in shear pattern, even in the absence of altered mean shear, represent a stimulus to acute change in endothelial function in healthy individuals. NEW & NOTEWORTHY Intermittent negative pressure applied to the forearm induced significant fluctuations in antegrade and retrograde shear rate, while mean shear was preserved relative to baseline. Our exploratory study revealed that brachial artery flow-mediated dilation was significantly improved following 30-min exposure to intermittent negative pressure. Fluctuations in blood flow or shear rate, with unaltered mean shear, may have important implications for vascular health; however, further research is required to identify the underlying mechanisms and potential long-term health benefits.

Contains fulltext : 215498.pdf (Publisher’s version ) (Open Access) BACKGROUND: Patients with primary aldosteronism (PA) experience more cardiovascular events compared to patients with essential hypertension (EHT), independent from blood pressure levels. In animals, mineralocorticoid receptor antagonists limit ischaemia-reperfusion (IR) injury by increasing extracellular adenosine formation and adenosine receptor stimulation. Adenosine is an endogenous compound with profound cardiovascular protective effects. Firstly, we hypothesized that patients with PA have lower circulating adenosine levels which might contribute to the observed increased cardiovascular risk. Secondly, we hypothesized that by this mechanism, patients with PA are more susceptible to IR compared to patients with EHT. DESIGN: In our prospective study in 20 patients with PA and 20 patients with EHT, circulating adenosine was measured using a pharmacological blocker solution that halts adenosine metabolism after blood drawing. Brachial artery flow-mediated dilation (FMD) before and after forearm IR was used as a well-established method to study IR injury. RESULTS: Patients with PA had a 33% lower adenosine level compared to patients with EHT (15.3 [13.3-20.4] vs 22.7 [19.4-36.8] nmol/L, respectively, P < .01). The reduction in FMD after IR, however, did not differ between patients with PA and patients with EHT (-1.0 +/- 2.9% vs -1.6 +/- 1.6%, respectively, P = .52). CONCLUSIONS: As adenosine receptor stimulation induces various powerful protective cardiovascular effects, its lower concentration in patients with PA might be an important novel mechanism that contributes to their increased cardiovascular risk. We suggest that modulation of the adenosine metabolism is an exciting novel pharmacological opportunity to limit cardiovascular risk in patients with PA that needs further exploration. 01 december 2019

Sympathetic nervous system activation elicits carotid artery vasodilation in healthy subjects, yet vasoconstriction in those with cardiovascular disease (CVD). Whether carotid artery vasoconstriction can be reversed is currently unknown. Nineteen subjects with increased risk for CVD were referred to a 12-week physical activity intervention, and 12 participants with increased risk for CVD were recruited as a no treatment control group. Cardiorespiratory and vascular health measures were collected at baseline and 12 weeks. Results indicate that carotid artery vasoconstriction in response to sympathetic stimulation may be reversed in subjects at increased risk of CVD. These findings warrant further investigation.

Introduction: Reperfusion is required to salvage ischaemic tissue, but also causes further damage (i.e., ischaemia/reperfusion-injury). Heart failure patients reveal exaggerated ischaemia/reperfusion-injury, whilst traditional ischaemic preconditioning cannot prevent ischaemia/reperfusion-injury. Exercise training may be a more powerful preconditioning stimulus, especially high-intensity interval training given the similarities with ischaemic preconditioning. Therefore, we examined the impact of 12-week continuous training vs. high-intensity interval training on brachial artery endothelial ischaemia/reperfusion-injury in heart failure patients New York Heart Association-class II-III.Methods: Twenty heart failure patients (male:female 19:1, 64 ± 8 years, ejection fraction 38 ± 6%) were allocated to 12-weeks of high-intensity interval training (10∗1-min 90% maximal workload – 2.5-min 30% maximal workload) or continuous training (30-min 60–75% maximal workload). Before and after the intervention, we measured brachial artery endothelial function with flow-mediated dilation (FMD) before and after ischaemia/reperfusion (5-min ischemic exercise, 15-min reperfusion).Results: Ischaemia/reperfusion caused a significant decline in FMD (continuous training (n = 10): 5.2 ± 2.5 to 3.4 ± 1.6%, high-intensity interval training (n = 10): 5.3 ± 2.6 to 3.5 ± 1.6%, P = 0.01), which was not different between groups (P > 0.05). Training improved maximal workload and fitness (P < 0.05), with no differences between groups (P > 0.05). Exercise training did not alter FMD (P > 0.05), whilst ischaemia/reperfusion did not impair FMD after exercise training (continuous training: 4.8 ± 3.0 to 4.2 ± 2.3%, high-intensity interval training: 4.7 ± 2.5 to 3.8 ± 2.3%, P > 0.05). No changes were found in FMD before or after ischaemia/reperfusion after 12-weeks in controls (n = 9).Conclusion: We found that 12-week exercise training in heart failure patients mitigated endothelial ischaemia-reperfusion injury, an effect independent of the type of exercise. These changes may contribute to the cardioprotective effects of exercise training, whilst our findings highlight the potency of exercise as a preconditioning stimulus.

Background Remote ischemic postconditioning (rIPostC) refers to the observation that repeated, short periods of ischemia protect remote areas against tissue damage during and after prolonged ischemia. Based on previous observations of a potential neuroprotective effect of rIPostC, the aim of this study is to evaluate whether repeated rIPostC after an ischemic stroke can reduce infarct size, which could be translated to an improvement in clinical outcomes. Methods/design We will enroll 200 ischemic stroke patients to daily rIPostC or sham conditioning during hospitalization into a randomized single-blind placebo-controlled trial. The intervention consists of twice daily exposure to four cycles of 5-min cuff inflation around the upper arm to > 20 mmHg above systolic blood pressure (i.e., rIPostC) or 50 mmHg (i.e., control), followed by 5 minutes of deflation. The primary outcome is infarct size, measured using an MRI diffusion-weighted image at the end of hospitalization. Secondary outcomes include the Modified Rankin Scale, National Institutes of Health Stroke Scale, quality of life, and cardiovascular and cerebrovascular morbidity and mortality. To explore possible underlying mechanisms of rIPostC, venous blood will be sampled to assess biomarkers of inflammation and vascular health. Discussion Previous studies in animals and humans, using a single bout of remote ischemic conditioning, report a potential effect of rIPostC in attenuating neural damage. Although repeated rIPostC has been investigated for cardiovascular disease patients and preclinical stroke models, no previous study has explored the potential physiological and clinical effects of repeatedly applying rIPostC during the hospitalization phase after a stroke. Trial registration Netherlands Trial Register, NTR6880. Registered on 8 December 2017. Electronic supplementary material The online version of this article (10.1186/s13063-019-3264-0) contains supplementary material, which is available to authorized users.

Objectives: To explore the preliminary effects and acceptability of a co-produced physical activity referral intervention. Study Design: Longitudinal design with data collected at baseline and post a 12-week physical activity referral intervention. Setting: Community leisure centre. Methods: In all, 32 adults with controlled lifestyle-related health conditions took part in a physical activity referral intervention (co-produced by a multidisciplinary stakeholder group) comprising 12 weeks subsidised fitness centre access plus four behaviour change consultations. A complete case analysis ( t-tests and magnitude-based inferences) was conducted to assess baseline-to-12-week change in physical activity, cardiometabolic, and psychological measures. Semi-structured interviews were conducted ( n = 12) to explore experiences of the intervention. Results: Mean improvements were observed in cardiorespiratory fitness (3.6 mL kg-1 min-1 [95% confidence interval: 1.9–5.4], p Conclusions: A co-produced physical activity referral intervention elicited short-term improvements in physical activity and cardiometabolic health. Further refinements may be required, via ongoing feedback between stakeholders, researchers and service users, to achieve the intended holistic physical activity focus of the intervention, prior to a definitive trial.

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.

Objective Acromegaly is characterized by an excess of growth hormone (GH) and insulin-like growth factor 1 (IGF1). Cardiovascular disease (CVD) risk factors are common in acromegaly and often persist after treatment. Both acute and long-lasting pro-inflammatory effects have been attributed to IGF1. Therefore, we hypothesized that inflammation persists in treated acromegaly and may contribute to CVD risk. Methods In this cross-sectional study, we assessed cardiovascular structure and function, and inflammatory parameters in treated acromegaly patients. Immune cell populations and inflammatory markers were assessed in peripheral blood from 71 treated acromegaly patients (with controlled or uncontrolled disease) and 41 matched controls. Whole blood (WB) was stimulated with Toll-like receptor ligands. In a subgroup of 21 controls and 33 patients with controlled disease, vascular ultrasound measurements were performed. Results Leukocyte counts were lower in patients with controlled acromegaly compared to patients with uncontrolled acromegaly and controls. Circulating IL18 concentrations were lower in patients; concentrations of other inflammatory mediators were comparable with controls. In stimulated WB, cytokine production was skewed toward inflammation in patients, most pronounced in those with uncontrolled disease. Vascular measurements in controlled patients showed endothelial dysfunction as indicated by a lower flow-mediated dilatation/nitroglycerine-mediated dilatation ratio. Surprisingly, pulse wave analysis and pulse wave velocity, both markers of endothelial dysfunction, were lower in patients, whereas intima-media thickness did not differ. Conclusions Despite treatment, acromegaly patients display persistent inflammatory changes and endothelial dysfunction, which may contribute to CVD risk and development of CVD.

Contains fulltext : 202688.pdf (Publisher’s version ) (Closed access) AIMS: Pulmonary hypertension (PH) is associated with high morbidity and mortality and the predictive capacity of traditional functional echocardiographic measures is poor. Recent studies assessed the predictive capacity of right ventricular longitudinal strain (RVLS). Diversity in methods between these studies resulted in conflicting outcomes. The purpose of this systematic review and meta-analysis was to determine the independent prognostic value of RVLS for PH-related events and all-cause mortality. METHODS AND RESULTS: A systematic search in Pubmed (MEDLINE), Embase, the Cochrane Library, and Web of Science was performed to identify studies that examined the prognostic value of RVLS in patients with PH. Studies reporting Cox regression based hazard ratios (HRs) for a combined endpoint of mortality and PH-related events or all-cause mortality for echocardiographic derived RVLS were included. A weighted mean of the multivariate HR was used to determine the independent predictive value of RVLS. Eleven studies met our criteria, including 1169 patients with PH (67% female, 0.6-3.8 years follow-up). PH patients with a relative reduction of RVLS of 19% had a significantly higher risk for the combined endpoint [HR 1.22, 95% confidence interval (CI) 1.07-1.40], while patients with a relative reduction of RVLS of 22% had a significantly higher risk for all-cause mortality (HR 2.96, 95% CI 2.00-4.38). CONCLUSION: This systematic review and meta-analysis showed that RVLS has independent prognostic value for a combined endpoint and all-cause mortality in patients with PH. Collectively, these findings emphasize that RVLS may have value for optimizing current predictive models for clinical events or mortality in patients with PH.

Aortic valve replacement (AVR) leads to remodeling of the left ventricle (LV). Adopting a novel technique to examine dynamic LV function, our study explored whether post-AVR changes in dynamic LV function and/or changes in aortic valve characteristics are associated with LV mass regression during follow-up. We retrospectively analyzed 30 participants with severe aortic stenosis who underwent standard transthoracic echocardiographic assessment before AVR [88 (IQR or interquartile range: 22–143) days], post-AVR [13 (6–22) days], and during follow-up [455 (226–907) days]. We assessed standard measures of LV structure, function, and aortic valve characteristics. Novel insight into dynamic LV function was provided through a four-chamber image by examination of the temporal relation between LV longitudinal strain (ε) and volume (ε-volume loops), representing the contribution of LV mechanics to volume change. AVR resulted in immediate changes in structural valve characteristics, alongside a reduced LV longitudinal peak ε and improved coherence between the diastolic and systolic part of the ε-volume loop (all P < 0.05). Follow-up revealed a decrease in LV mass ( P < 0.05) and improvements in LV ejection fraction and LV longitudinal peak ε ( P < 0.05). A significant relationship was present between decline in LV mass during follow-up and post-AVR improvement in coherence of the ε-volume loops ( r = 0.439, P = 0.03), but not with post-AVR changes in aortic valve characteristics or LV function (all P > 0.05). We found that post-AVR improvements in dynamic LV function are related to long-term remodeling of the LV. This highlights the potential importance of assessing dynamic LV function for cardiac adaptations in vivo. NEW & NOTEWORTHY Combining temporal measures of left ventricular longitudinal strain and volume (strain-volume loop) provides novel insights in dynamic cardiac function. In patients with aortic stenosis who underwent aortic valve replacement, postsurgical changes in the strain-volume loop are associated with regression of left ventricular mass during follow-up. This provides novel insight into the relation between postsurgery changes in cardiac hemodynamics and long-term structural remodeling, but also supports the potential utility of the assessment of dynamic cardiac function.

Progression of atrial fibrillation (AF) is associated with worsened prognosis for cardiovascular events and mortality. Exercise-based-cardiac rehabilitation programmes have shown preliminary promise for primary and secondary prevention of AF. Yet, such interventions are typically reserved for patients with acute coronary syndrome or undergoing revascularization. Using a retrospective cohort design, the present study investigated the association of exercise-based cardiac rehabilitation on the progression of paroxysmal to sustained AF, compared to propensity-matched controls. Patients with a diagnosis of paroxysmal AF were compared between those with and without an electronic medical record of exercise-based cardiac rehabilitation within 6-months of diagnosis. Using cox regression models, we ascertained odds of 2-year incidence for AF progression. This cohort of 9808 patients with paroxysmal AF demonstrated that exercise-based cardiac rehabilitation was associated with 26% lower odds of AF progression (odds ratio 0.74, 95% CI 0.66–0.83) compared to propensity-matched controls. This beneficial effect seemed to vary across patient subgroups. In conclusion, findings revealed that exercise-based cardiac rehabilitation was associated with significantly lower odds of progression from paroxysmal to sustained AF at 2-years follow-up compared to propensity-matched controls.

Background. This is a formative evaluation study of the HERizon Project, a home-based multi-component physical activity (PA) intervention for adolescent girls in the UK and Ireland. Although not intended, this study coincided with the initial COVID-19 lockdown restrictions. Methods. A total of 42 female participants, aged 13 to 16 years old (mean = 14.2, SD = 1.1), were randomly allocated to: (i) the HERizon group (n = 22) or (ii) the wait-list control group (n = 20). Participants in the six-week HERizon group were asked to complete three PA sessions each week and engage in weekly behaviour change support video calls. The primary outcome measure was self-reported habitual PA. Secondary outcomes measures included cardiorespiratory fitness (20 m shuttle run), muscular strength (standing long jump), muscular endurance (push up test), and psychosocial outcomes (Perceived Competence Scale, Body Appreciation Scale, Self-Esteem Questionnaire, Behavioural Regulation in Exercise Questionnaire). Quantitative and qualitative process evaluation data were also collected. Outcome measures were assessed at baseline and after the six-week intervention. Results. There was no significant change in habitual PA between groups (LMM group*time interaction: p = 0.767). The HERizon group had significantly increased cardiorespiratory fitness (p = 0.001), muscular endurance (p = 0.022), intrinsic motivation (p = 0.037), and body appreciation (p &lt, 0.003) in comparison to the wait-list control group. All participants in the intervention group completed the intervention and compliance to the intervention was high (participants completed 18 &plusmn, 2 sessions). Conclusions. Although no change in PA was observed, HERizon resulted in improved physical fitness and psychosocial outcomes. These preliminary findings, alongside positive findings for feasibility and acceptability, highlight potential benefits from the home-based intervention, thus further investigation is warranted.

What is the topic of this review? This review discusses the effects of repeated exposure of tissue to ischaemic preconditioning on cardiovascular function, the attendant adaptations and their potential clinical relevance. What advances does it highlight? We discuss the effects of episodic exposure to ischaemic preconditioning to prevent and/or attenuate ischaemic injury and summarize evidence pertaining to improvements in cardiovascular function and structure. Discussion is provided regarding the potential mechanisms that contribute to both local and systemic adaptation. Findings suggest that clinical benefits result from both the prevention of ischaemic events and the attenuation of their consequences. Ischaemic preconditioning (IPC) refers to the phenomenon whereby short periods of cyclical tissue ischaemia confer subsequent protection against ischaemia-induced injury. As a consequence, IPC can ameliorate the myocardial damage following infarction and can reduce infarct size. The ability of IPC to confer remote protection makes IPC a potentially feasible cardioprotective strategy. In this review, we discuss the concept that repeated exposure of tissue to IPC may increase the 'dose' of protection and subsequently lead to enhanced protection against ischaemia-induced myocardial injury. This may be relevant for clinical populations, who demonstrate attenuated efficacy of IPC to prevent or attenuate ischaemic injury (and therefore myocardial infarct size). Furthermore, episodic IPC facilitates repeated exposure to local (e.g. shear stress) and systemic stimuli (e.g. hormones, cytokines, blood-borne substances), which may induce improvement in vascular function and health. Such adaptation may contribute to prevention of cardio- and cerebrovascular events. The clinical benefits of repeated IPC may, therefore, result from both the prevention of ischaemic events and the attenuation of their consequences. We provide an overview of the literature pertaining to the impact of repeated IPC on cardiovascular function, related to both local and remote adaptation, as well as potential clinical implications.

What is the topic of this review? This brief review discusses potential sex differences in arterial function across the age span, with special emphasis on the effects of oestrogen and testosterone on the vascular endothelium. What advances does it highlight? We discuss the relationship between the impacts of sex hormones on arterial function and health in the context of epidemiological evidence pertaining to the menopause and ageing. Studies performed in humans are emphasized, alongside insights from animal studies. Findings suggest that the combination of exercise and hormone administration should be potentially synergistic or additive in humans. This brief review presents historical evidence for the purported impacts of male and female sex hormones on the vasculature in humans, including effects on macro- and microvascular function and health. Impacts of ageing on hormonal changes and arterial function are considered in the context of the menopause. Physiological data are presented alongside clinical outcomes from large trials, in an attempt to rationalize disparate findings along the bench-to-bedside continuum. Finally, the theoretical likelihood that exercise and hormone treatment may induce synergistic and/or additive vascular adaptations is developed in the context of recent laboratory studies that have compared male and female responses to training. Differences between men and women in terms of the impact of age and cardiorespiratory fitness on endothelial function are addressed. Ultimately, this review highlights the paucity of high-quality and compelling evidence regarding the fundamental impact, in humans, of sex differences on arterial function and the moderating impacts of exercise on arterial function, adaptation and health at different ages in either sex.

Item does not contain fulltext STUDY DESIGN: Retrospective study. OBJECTIVES: To model the effect of time since injury on longitudinal respiratory function measures in spinal cord injured-individuals and to investigate the effect of patient characteristics. SETTING: A total of 173 people who sustained a spinal cord injury between 1966 and April 2013 and who had previously participated in research or who underwent clinically indicated outpatient respiratory function tests at the Austin Hospital in Melbourne, Australia, were included in the study. At least two measurements over time were available for analysis in 59 patients. METHODS: Longitudinal data analysis was performed using generalised linear regression models to determine changes in respiratory function following spinal cord injury from immediately post injury to many years later. Secondly, we explored whether injury severity, age, gender and body mass index (BMI) at injury altered the time-dependent change in respiratory function. RESULTS: The generalised linear regression model showed no significant change (P=0.276) in respiratory function measured in (forced) vital capacity ((F)VC) after the spinal cord injury. However, significant (P30 kg m-2.Spinal Cord advance online publication, 12 January 2016; doi:10.1038/sc.2015.233.

Item does not contain fulltext OBJECTIVES: Brachial artery flow-mediated dilation (FMD) is a popular technique to examine endothelial function in humans. Identifying volunteer and methodological factors related to variation in FMD is important to improve measurement accuracy and applicability. METHODS: Volunteer-related and methodology-related parameters were collected in 672 volunteers from eight affiliated centres worldwide who underwent repeated measures of FMD. All centres adopted contemporary expert-consensus guidelines for FMD assessment. After calculating the coefficient of variation (%) of the FMD for each individual, we constructed quartiles (n = 168 per quartile). Based on two regression models (volunteer-related factors and methodology-related factors), statistically significant components of these two models were added to a final regression model (calculated as beta-coefficient and R). This allowed us to identify factors that independently contributed to the variation in FMD%. RESULTS: Median coefficient of variation was 17.5%, with healthy volunteers demonstrating a coefficient of variation 9.3%. Regression models revealed age (beta = 0.248, P < 0.001), hypertension (beta = 0.104, P < 0.001), dyslipidemia (beta = 0.331, P < 0.001), time between measurements (beta = 0.318, P < 0.001), lab experience (beta = -0.133, P < 0.001) and baseline FMD% (beta = 0.082, P < 0.05) as contributors to the coefficient of variation. After including all significant factors in the final model, we found that time between measurements, hypertension, baseline FMD% and lab experience with FMD independently predicted brachial artery variability (total R = 0.202). CONCLUSION: Although FMD% showed good reproducibility, larger variation was observed in conditions with longer time between measurements, hypertension, less experience and lower baseline FMD%. Accounting for these factors may improve FMD% variability. 01 september 2016

Introduction: The ability of ischemic preconditioning (IPC) to enhance exercise capacity may be mediated through altering exercise-induced blood flow and/or vascular function. This study investigated the hypothesis that (local) IPC enhances exercise-induced blood flow responses and prevents decreases in vascular function following exercise.Methods: Eighteen healthy, recreationally trained, male participants (mean ±SD: age 32 ± 8 years; BMI 24.2 ± 2.3; blood pressure 122 ± 10/72 ± 8 mmHg; resting HR 58 ± 9 beats min-1) received IPC (220 mmHg; 4 × 5-min bilateral arms), REMOTE IPC (220 mmHg; 4 × 5-min bilateral legs), or SHAM (20 mmHg; 4 × 5-min bilateral arms) in a counterbalanced order prior to 30-min of submaximal (25% maximal voluntary contraction) unilateral rhythmic handgrip exercise. Brachial artery diameter and blood flow were assessed every 5-min throughout the 30-min submaximal exercise using high resolution ultrasonography. Pre- and post-exercise vascular function was measured using flow-mediated dilation (FMD).Results: IPC resulted in enlarged brachial artery diameter during exercise [0.016 cm (0.003–0.03 cm), P = 0.015] compared to REMOTE IPC, but blood flow during exercise was similar between conditions (P > 0.05). Blood flow (l/min) increased throughout exercise (time: P < 0.005), but there was no main effect of condition (P = 0.29) or condition ∗ time interaction (P = 0.83). Post-exercise FMD was similar between conditions (P > 0.05).Conclusion: Our data show that local (but not remote) IPC, performed as a strategy prior to exercise, enhanced exercise-induced conduit artery diameter dilation, but these changes do not translate into increased blood flow during exercise nor impact post-exercise vascular function.

Objective Functional electrical stimulation (FES) may help to reduce the risk of developing macrovascular and microvascular complications in people with spinal cord injury. Low-intensity FES has significant clinical potential because this can be applied continuously throughout the day. This study examines the acute effects of low-intensity FES using wearable clothing garment on vascular blood flow and oxygen consumption in people with spinal cord injury. Design This was a cross-sectional observation study. Methods Eight participants with a motor complete spinal cord injury received four 3-min unilateral FES to the gluteal and hamstring muscles. Skin and deep femoral artery blood flow and oxygen consumption were measured at baseline and during each bout of stimulation. Results Femoral artery blood flow increased by 18.1% with the application of FES (P = 0.02). Moreover, femoral artery blood flow increased further during each subsequent block of FES (P = 0.004). Skin perfusion did not change during an individual block of stimulation (P = 0.66). Skin perfusion progressively increased with each subsequent bout (P < 0.001). There was no change in femoral or skin perfusion across time in the nonstimulated leg (all P > 0.05). Conclusion Low-intensity FES acutely increased blood flow during stimulation, with a progressive increase across subsequent FES bouts. These observations suggest that continuous, low-intensity FES may represent a practical and effective strategy to improve perfusion and reduce the risk of vascular complications.

Introduction: Ischemic preconditioning (IPC) may enhance endurance performance. No previous study has directly compared distinct IPC protocols for optimal benefit. Purpose: To determine whether a specific IPC protocol (ie, number of cycles, amount of muscle tissue, and local vs remote occlusion) elicits greater performance outcomes. Methods: Twelve cyclists performed 5 different IPC protocols 30 min before a blinded 375-kJ cycling time trial (TT) in a laboratory. Responses to traditional IPC (4 × 5-min legs) were compared with those to 8 × 5-min legs and sham (dose cycles), 4 × 5-min unilateral legs (dose tissue), and 4 × 5-min arms (remote). Rating of perceived exertion and blood lactate were recorded at each 25% TT completion. Power (W), heart rate (beats/min), and oxygen uptake () (mL · kg−1 · min−1) were measured continuously throughout TTs. Magnitude-based-inference statistics were employed to compare variable differences to the minimal practically important difference. Results: Traditional IPC was associated with a 17-s (0, 34) faster TT time than sham. Applying more dose cycles (8 × 5 min) had no impact on performance. Traditional IPC was associated with likely trivial higher blood lactate and possibly beneficial lower responses vs sham. Unilateral IPC was associated with 18-s (−11, 48) slower performance than bilateral (dose tissue). TT times after remote and local IPC were not different (0 [−16, 16] s). Conclusion: The traditional 4 × 5-min (local or remote) IPC stimulus resulted in the fastest TT time compared with sham; there was no benefit of applying a greater number of cycles or employing unilateral IPC.

Item does not contain fulltext PURPOSE: Exercise training induces adaptation in conduit and resistance arteries in humans, partly as a consequence of repeated elevation in blood flow and shear stress. The stimuli associated with intrinsic cutaneous microvascular adaptation to exercise training have been less comprehensively studied. METHODS: We studied 14 subjects who completed 8-weeks cycle ergometer training, with partial cuff inflation on one forearm to unilaterally attenuate cutaneous blood flow responses during each exercise-training bout. Before and after training, bilateral forearm skin microvascular dilation was determined using cutaneous vascular conductance (CVC: skin flux/blood pressure) responses to gradual localised heater disk stimulation performed at rest (33, 40, 42 and 44 degrees C). RESULTS: Cycle exercise induced significant increases in forearm cutaneous flux and temperature, which were attenuated in the cuffed arm (2-way ANOVA interaction-effect; P < 0.01). We found that forearm CVC at 42 and 44 degrees C was significantly lower in the uncuffed arm following 8-weeks of cycle training (P < 0.01), whereas no changes were apparent in the contralateral cuffed arm (P = 0.77, interaction-effect P = 0.01). CONCLUSIONS: Lower limb exercise training in healthy young men leads to lower CVC-responses to a local heating stimulus, an adaptation mediated, at least partly, by a mechanism related to episodic increases in skin blood flow and/or skin temperature. 01 april 2018

Carotid artery (CCA) dilation occurs in healthy subjects during cold pressor test (CPT), while the magnitude of dilation relates to cardiovascular risk. To further explore this phenomenon and mechanism, we examined carotid artery responses to different sympathetic tests, with and without α1-receptor blockade and assessed similarity to these responses between carotid and coronary arteries. In randomized order, 10 healthy participants (25 ± 3 yr) underwent sympathetic stimulation using the CPT (3-min left-hand immersion in ice-slush) and lower-body negative pressure (LBNP). Before and during sympathetic tests, CCA diameter and velocity (Doppler ultrasound) and left anterior descending (LAD) coronary artery velocity (echocardiography) were recorded across 3 min. Measures were repeated 90 min following selective α1-receptor blockade via oral prazosin (0.05 mg/kg body wt). CPT significantly increased CCA diameter, LAD maximal velocity, and velocity-time integral area-under-the-curve (all P < 0.05). In contrast, LBNP resulted in a decrease in CCA diameter, LAD maximal velocity, and velocity time integral (VTI; all P < 0.05). Following α1-receptor blockade, CCA and LAD velocity responses to CPT were diminished. In contrast, during LBNP (−30 mmHg), α1-receptor blockade did not alter CCA or LAD responses. Finally, changes in CCA diameter and LAD VTI responses to sympathetic stimulation were positively correlated ( r = 0.66, P < 0.01). We found distinct carotid artery responses to different tests of sympathetic stimulation, where α1 receptors partly contribute to CPT-induced responses. Finally, we found agreement between carotid and coronary artery responses. These data indicate similarity between carotid and coronary responses to sympathetic tests and the role of α1 receptors that is dependent on the nature of the sympathetic challenge. NEW & NOTEWORTHY We showed distinct carotid artery responses to cold pressor test (CPT; i.e., dilation) and lower-body negative pressure (LBNP; i.e., constriction). Blockade of α1-receptors significantly attenuated dilator responses in carotid and coronary arteries during CPT, while no changes were found during LBNP. Our findings indicate strong similarity between carotid and coronary artery responses to distinct sympathetic stimuli, and for the role of α-receptors.

Item does not contain fulltext Importance: Exercise reduces the risk of cardiovascular events, including through an underrecognized, clinically useful form of acute cardioprotection accessible after a single episode of exercise, which is called cardiovascular preconditioning. Observations: Preclinical evidence shows that 1 to 3 episodes of exercise per week will provide strong cardioprotection; gradual, modest cardiovascular risk factor modification or physiological artery remodeling cannot fully explain these benefits. This review highlights preclinical evidence that acute exercise-induced cardiac preconditioning has the ability to activate multiple pathways to confer immediate protection against ischemic events, reduce the severity of potentially lethal ischemic myocardiac injury, and act as a physiological first line of defense. Conclusions and Relevance: Independent of the protective benefits of long-term exercise training on risk factors and adaptation of the cardiovascular system, cardiovascular preconditioning may contribute to the immediate cardioprotection of exercise. In practical terms, this means that 1 episode of exercise can create clinically relevant cardioprotection.