The purpose of this study was to examine the effect of an acute bout of prolonged sitting with and without exercise breaks on cerebrovascular function in 7‐ to 13‐year‐old children. Forty‐two ...children and adolescents were recruited to a crossover trial, with 15 girls (mean age 10.1 ± 2.5 years) and 16 boys (mean age 10.5 ± 1.3 years) completing the two trial conditions: SIT, uninterrupted sitting for 3 h and CYCLE, 3 h of sitting interrupted hourly with a 10‐min moderate intensity exercise break. Cerebrovascular function was measured Pre and Post SIT and CYCLE from blood flow (Q̇${\dot{Q}}$), diameter, and shear rate of the internal carotid artery (ICA) at rest and in response to CO2. Blood velocity in the middle (MCA) and posterior (PCA) cerebral arteries was assessed at rest, during a neurovascular coupling task (NVC) and in response to CO2. We demonstrate that SIT but not CYCLE reduced ICA cerebrovascular reactivity to CO2 (%Δ ICA Q̇${\dot{Q}}$/Δ end‐tidal CO2: SIT: Pre 5.0 ± 2.4%/mmHg to Post 3.3 ± 2.8%/mmHg vs. CYCLE: Pre 4.4 ± 2.3%/mmHg to Post 5.3 ± 3.4%/mmHg, P = 0.05) and slowed the MCA blood velocity onset response time to hypercapnia (SIT: Pre 57.2 ± 32.6 s to Post 76.6 ± 55.2 s, vs. CYCLE: Pre 64.1 ± 40.4 s to Post 52.3 ± 28.8 s, P = 0.05). There were no changes in NVC. Importantly, breaking up prolonged sitting with hourly exercise breaks prevented the reductions in cerebrovascular reactivity to CO2 and the slowed intracranial blood velocity onset response time to hypercapnia apparent with uninterrupted sitting in children.
New Findings
What is the central question of this study?
What are the effects of interrupting prolonged sitting on cerebrovascular function in children?
What is the main finding and its importance?
Prolonged sitting results in declines in cerebrovascular reactivity, a valuable index of cerebrovascular health. Breaking up prolonged sitting with hourly 10 min exercise breaks prevented these changes. These initial findings suggest excessive sedentary behaviour does impact cerebrovascular function in childhood, but taking exercise breaks prevents declines.
The execution of clinical trials can be expensive and present logistical challenges regarding recruitment and retention of participants. Innovative research design fostering convenience by ...eliminating research facility visits may enhance recruitment and retention. We examined the feasibility of a remote clinical trial in people living with type 2 diabetes (T2D) . People with recently diagnosed T2D were recruited across the UK and Canada to the MOTIVATE T2D trial (NCT04653532) ; a feasibility randomised controlled trial investigating two exercise and physical activity interventions. Participants received a self-testing kit, via mail, at baseline and post-intervention (6 months) . Measures included, HbA1c, lipid profile, anthropometrics and blood pressure and 14-day flash glucose and physical activity monitoring. Between Jan 2021 and Jan 2022 286 patients were eligible, of whom 110 (UK n=63, Can n=47, male n=58, white n=95) consented. Mean journey time from research facilities was ≤1h in 18%, 1-2h in 50% and >2h in 33% of participants. Availability of outcome data is presented in Table 1. Remote testing resulted in benefits to recruitment and good participant retention and protocol adherence. As such, remote clinical trials are feasible in people with T2D and future clinical trials should consider a remote clinical trial based approach as an alternative to conventional designs.
Disclosure
A. P. Davies: None. K. Hesketh: None. J. Low: None. V. S. Sprung: None. H. Jones: None. A. M. Mcmanus: None. M. Cocks: None. Motivate team: n/a.
Funding
UK Medical Research Council (MR/T032189/1) , Canadian Institute for Health Research (UCD-170587)
New Findings
What is the central question of this study?
Gonadal hormones modulate cerebrovascular function while insulin‐like growth factor 1 (IGF‐1) facilitates exercise‐mediated cerebral ...angiogenesis; puberty is a critical period of neurodevelopment alongside elevated gonadal hormone and IGF‐1 activity: but whether exercise training across puberty enhances cerebrovascular function is unkown.
What is the main finding and its importance?
Cerebral blood flow is elevated in endurance trained adolescent males when compared to untrained counterparts. However, cerebrovascular reactivity to hypercapnia is faster in trained vs. untrained children, but not adolescents. Exercise‐induced improvements in cerebrovascular function are attainable as early as the first decade of life.
Global cerebral blood flow (gCBF) and cerebrovascular reactivity to hypercapnia (CVRCO2${\mathrm{CV}}{{\mathrm{R}}_{{\mathrm{C}}{{\mathrm{O}}_{\mathrm{2}}}$) are modulated by gonadal hormone activity, while insulin‐like growth factor 1 facilitates exercise‐mediated cerebral angiogenesis in adults. Whether critical periods of heightened hormonal and neural development during puberty represent an opportunity to further enhance gCBF and CVRCO2${\mathrm{CV}}{{\mathrm{R}}_{{\mathrm{C}}{{\mathrm{O}}_{\mathrm{2}}}$ is currently unknown. Therefore, we used duplex ultrasound to assess gCBF and CVRCO2${\mathrm{CV}}{{\mathrm{R}}_{{\mathrm{C}}{{\mathrm{O}}_{\mathrm{2}}}$ in n = 128 adolescents characterised as endurance‐exercise trained (males: n = 30, females: n = 36) or untrained (males: n = 29, females: n = 33). Participants were further categorised as pre‐ (males: n = 35, females: n = 33) or post‐ (males: n = 24, females: n = 36) peak height velocity (PHV) to determine pubertal or ‘maturity’ status. Three‐factor ANOVA was used to identify main and interaction effects of maturity status, biological sex and training status on gCBF and CVRCO2${\mathrm{CV}}{{\mathrm{R}}_{{\mathrm{C}}{{\mathrm{O}}_{\mathrm{2}}}$. Data are reported as group means (SD). Pre‐PHV youth demonstrated elevated gCBF and slower CVRCO2${\mathrm{CV}}{{\mathrm{R}}_{{\mathrm{C}}{{\mathrm{O}}_{\mathrm{2}}}$ mean response times than post‐PHV counterparts (both: P ≤ 0.001). gCBF was only elevated in post‐PHV trained males when compared to untrained counterparts (634 (43) vs. 578 (46) ml min−1; P = 0.007). However, CVRCO2${\mathrm{CV}}{{\mathrm{R}}_{{\mathrm{C}}{{\mathrm{O}}_{\mathrm{2}}}$ mean response time was faster in pre‐ (72 (20) vs. 95 (29) s; P ≤ 0.001), but not post‐PHV (P = 0.721) trained youth when compared to untrained counterparts. Cardiorespiratory fitness was associated with gCBF in post‐PHV youth (r2 = 0.19; P ≤ 0.001) and CVRCO2${\mathrm{CV}}{{\mathrm{R}}_{{\mathrm{C}}{{\mathrm{O}}_{\mathrm{2}}}$ mean response time in pre‐PHV youth (r2 = 0.13; P = 0.014). Higher cardiorespiratory fitness during adolescence can elevate gCBF while exercise training during childhood primes the development of cerebrovascular function, highlighting the importance of exercise training during the early stages of life in shaping the cerebrovascular phenotype.
To investigate scaling approaches for evaluating the development of peak VO2 and improving the identification of low cardiopulmonary fitness in Southern Chinese children and adolescents.
Nine hundred ...and twenty Chinese children and adolescents (8 to 16 years) underwent graded cardiopulmonary exercise test on a treadmill until volitional exhaustion. Peak VO2 was corrected for the effects of body mass by ratio or allometric scaling. Z score equations for predicting peak VO2 were developed. Correlations between scaled peak VO2, z scores, body size and age were tested to examine the effectiveness of the approach.
Eight hundred and fifty-two participants (48% male) were included in the analyses. Absolute peak VO2 significantly increased with age in both sexes (both P<0.05), while ratio-scaled peak VO2 increased only in males (P<0.05). Allometrically scaled peak VO2 increased from 11 years in both sexes, plateauing by 12 years in girls and continuing to rise until 15 years in boys. Allometically scaled peak VO2 was not correlated with body mass, but remained correlated with height and age in all but the older girls. Peak VO2 z score was not correlated with body mass, height or age.
Absolute and allometric scaled peak VO2 values are provided for Hong Kong Chinese children and adolescents by age and sex. Peak VO2 z scores improve the evaluation of cardiopulmonary fitness, allowing comparisons across ages and sex and will likely provide a better metric for tracking change over time in children and adolescents, regardless of body size and age.
New Findings
What is the central question of this study?
Children are spending more than 60% of their waking day sedentary. The consequences of excessive sedentary behaviour are not well understood ...in the child, but there is growing evidence that with increasing sedentary time, cardiovascular risk in childhood also increases.
What is the main finding and its importance?
Our findings show that a 3 h period of uninterrupted sitting causes a profound (33%) reduction in vascular function in young girls. Importantly, we also demonstrate that breaking up sitting with regular exercise breaks can prevent this.
Excessive sedentary behaviour has serious clinical and public health implications; however, the physiological changes that accompany prolonged sitting in the child are not completely understood. Herein, we examined the acute effect a prolonged period of sitting has upon superficial femoral artery function in 7‐ to 10‐year‐old girls and the impact of interrupting prolonged sitting with exercise breaks. Superficial femoral artery endothelium‐dependent flow‐mediated dilatation, total shear rate, anterograde and retrograde shear rates and oscillatory shear index were assessed before and after two experimental conditions: a 3 h uninterrupted period of sitting (SIT) and a 3 h period of sitting interrupted each hour with 10 min of moderate‐intensity exercise (EX). A mixed‐model analysis of variance was used to compare between‐condition and within‐condition main effects, controlling for the within‐subject nature of the experiment by including random effects for participant. Superficial femoral artery endothelium‐dependent flow‐mediated dilatation decreased significantly from pre‐ to post‐SIT (mean difference 2.2% flow‐mediated dilatation; 95% confidence interval = 0.60–2.94%, P < 0.001). This relative decline of 33% was abolished in the EX intervention. Shear rates were not significantly different within conditions. Our data demonstrate the effectiveness of short but regular exercise breaks in offsetting the detrimental effects of uninterrupted sitting in young girls.
New Findings
What is the central question of this study?
In this study, we investigated intracranial cerebrovascular and ventilatory reactivity to 6% CO2 in children and adults and explored dynamic ...ventilatory and cerebrovascular onset responses.
What is the main finding and its importance?
We showed that cerebrovascular reactivity was similar in children and adults, but the intracranial blood velocity onset response was markedly attenuated in children. Sex differences were apparent, with greater increases in intracranial blood velocity in females and lower ventilatory reactivity in adult females. Our study confirms the importance of investigating dynamic onset responses when assessing the influence of development on cerebrovascular regulation.
The purpose of this study was to compare the integrated intracranial cerebrovascular reactivity (CVR) and hypercapnic ventilatory response between children and adults and to explore the dynamic response of the middle cerebral artery mean velocity (MCAV). Children (n = 20; 9.9 ± 0.7 years of age) and adults (n = 21; 24.4 ± 2.0 years of age) completed assessment of CVR over 240 s using a fixed fraction of inspired CO2 (0.06). Baseline MCAV was higher in the adult females compared with the males (P ≤ 0.05). The MCAV was greater in female children compared with male children (P ≤ 0.05) and in female adults compared with male adults (P ≤ 0.05) with hypercapnia. Relative CVR was similar in children and adults (3.71 ± 1.06 versus 4.12 ± 1.32% mmHg−1; P = 0.098), with absolute CVR being higher in adult females than males (3.27 ± 0.86 versus 2.53 ± 0.70 cm s−1 mmHg−1; P ≤ 0.001). Likewise, the hypercapnic ventilatory response did not differ between the children and adults (1.89 ± 1.00 versus 1.77 ± 1.34 l min−1 mmHg−1; P = 0.597), but was lower in adult females than males (1.815 ± 0.37 versus 2.33 ± 1.66 l min−1 mmHg−1; P ≤ 0.05). The heart rate response to hypercapnia was greater in children than in adults (P = 0.001). A monoexponential regression model was used to characterize the dynamic onset, consisting of a delay term, amplitude and time constant (τ). The results revealed that MCAV τ was faster in adults than in children (34 ± 18 versus 74 ± 28 s; P = 0.001). Our study provides new insight into the impact of age and sex on CVR and the dynamic response of the MCAV to hypercapnia.
Intracranial blood velocity reactivity to a steady‐state hypercapnic stimulus has been shown to be similar in children and adults, but the onset response to hypercapnia is slower in the child. Given ...the vasodilatory effect of hypercapnia on the cerebrovasculature, assessment of vessel diameter, and blood flow are vital to fully elucidate whether the temporal hypercapnic response differs in children versus adults. Assessment of internal carotid artery (ICA) vessel diameter (ICAd), blood velocity (ICAv), volumetric blood flow (QICA), and shear rate (ICASR) in response to a 4 min hypercapnic challenge was completed in children (n = 14, 8 girls; 9.8 ± 0.7 years) and adults (n = 17, 7 females; 24.7 ± 1.8 years). The dynamic onset responses of partial pressure of end‐tidal CO2 (PETCO2), QICA, ICAv, and ICASR to hypercapnia were modeled, and mean response time (MRT) was computed. Following 4 min of hypercapnia, ICA reactivity and ICAd were comparable between the groups. Despite a similar MRT in PETCO2 in children and adults, children had slower QICA (children 108 ± 60 s vs. adults 66 ± 37 s; p = 0.023), ICAv (children 120 ± 52 s vs. adults 52 ± 31 s; p = 0.001), and ICASR (children 90 ± 27 s vs. adults 47 ± 36 s; p = 0.001) MRTs compared with adults. This is the first study to show slower hypercapnic hyperemic kinetic responses of the ICA in children. The mechanisms determining these differences and the need to consider the duration of hypercapnic exposure when assessing CVR in children should be considered in future studies.
Differences in the temporality of cerebrovascular vasomotion between children and adults may explain previously noted distinctions in the dynamic middle cerebral artery onset response to hypercapnia. This study shows slower hypercapnic onset mean response times for internal carotid artery velocity, flow and shear rate in children compared to adults. Although dilation of the internal carotid artery was similar in children and adults after 4 minutes of hypercapnia, the onset diameter response could not be modelled.
We explored the influence of sex and maturation on resting cervical artery hemodynamics (common carotid artery, CCA; internal carotid artery, ICA; and vertebral artery, VA), free-living physical ...activity, and sedentary behavior in children 6-17 yr of age. In addition, we investigated the relationship between physical activity, sedentary behavior, and cervical artery hemodynamics. Seventy-eight children and adolescents, girls (
= 42; mean age, 11.4 ± 2.5 yr) and boys (
= 36; mean age, 11.0 ± 2.6 yr), completed anthropometric measures, duplex ultrasound assessment of the cervical arteries, and wore an activPAL accelerometer to assess physical activity (indexed by steps/day) and sedentary behavior for 7 days. The ICA and VA diameters were similar between prepubertal and pubertal groups, as was volumetric blood flow (
); however, the CCA diameter was significantly larger in the pubertal group (
< 0.05). Boys were found to have larger diameters in all cervical arteries than girls, as well as higher
,
, and global cerebral blood flow (
< 0.05). The pubertal group was more sedentary (100 min/day more;
< 0.05) and took 3,500 fewer steps/day than the prepubertal group (
< 0.05). Shear rate (SR) and
of the cervical arteries showed no relationship to physical activity or prolonged bouts of sedentary behavior; however, a significant negative relationship was apparent between total sedentary time and internal carotid artery shear rate (ICA
) after covarying for steps/day and maturation (
< 0.05). These findings provide novel insight into the potential influence sedentary behavior may have on cerebrovascular blood flow in healthy girls and boys.
Cerebral blood flow is known to change with age; however, assessing these age-related changes is complex and requires consideration of pubertal status. This, to our knowledge, is the first study to investigate the influence of sex and maturation on resting cervical artery hemodynamics and subsequently explore associations with physical activity and sedentary behavior in healthy children and adolescents. Our findings suggest that habitual sedentary behavior may influence cervical artery hemodynamics in youth, independent of physical activity, maturation, and sex.
Neurovascular coupling (NVC) is mediated via nitric oxide signaling, which is independently influenced by sex hormones and exercise training. Whether exercise training differentially modifies NVC ...pre- versus postpuberty, where levels of circulating sex hormones will differ greatly within and between sexes, remains to be determined. Therefore, we investigated the influence of exercise training status on resting intracranial hemodynamics and NVC at different stages of maturation. Posterior and middle cerebral artery velocities (PCA
and MCA
) and pulsatility index (PCA
and MCA
) were assessed via transcranial Doppler ultrasound at rest and during visual NVC stimuli.
= 121 exercise-trained (males,
= 32; females,
= 32) and untrained (males,
= 28; females,
= 29) participants were characterized as pre (males,
= 33; females,
= 29)- or post (males,
= 27; females,
= 32)-peak height velocity (PHV). Exercise-trained youth demonstrated higher resting MCA
(
= 0.010). Maturity and training status did not affect the ΔPCA
and ΔMCA
during NVC. However, pre-PHV untrained males (19.4 ± 13.5 vs. 6.8 ± 6.0%;
≤ 0.001) and females (19.3 ± 10.8 vs. 6.4 ± 7.1%;
≤ 0.001) had a higher ΔPCA
during NVC than post-PHV untrained counterparts, whereas the ΔPCA
was similar in pre- and post-PHV trained youth. Pre-PHV untrained males (19.4 ± 13.5 vs. 7.9 ± 6.0%;
≤ 0.001) and females (19.3 ± 10.8 vs. 11.1 ± 7.3%;
= 0.016) also had a larger ΔPCA
than their pre-PHV trained counterparts during NVC, but the ΔPCA
was similar in trained and untrained post-PHV youth. Collectively, our data indicate that exercise training elevates regional cerebral blood velocities during youth, but training-mediated adaptations in NVC are only attainable during early stages of adolescence. Therefore, childhood provides a unique opportunity for exercise-mediated adaptations in NVC.
We report that the change in cerebral blood velocity during a neurovascular coupling task (NVC) is similar in pre- and postpubertal youth, regardless of exercise-training status. However, prepubertal untrained youth demonstrated a greater increase in cerebral blood pulsatility during the NVC task when compared with their trained counterparts. Our findings highlight that childhood represents a unique opportunity for exercise-mediated adaptations in cerebrovascular hemodynamics during NVC, which may confer long-term benefits in cerebrovascular function.
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