FLOW-MEDIATED DILATION IS MODIFIED BY EXERCISE TRAINING STATUS DURING CHILDHOOD AND ADOLESCENCE: PRELIMINARY EVIDENCE OF THE YOUTH ATHLETE'S ARTERY.

Chronic exercise training is associated with an 'athlete's artery' phenotype in young adults and an attenuated age-related decline in endothelium-dependent arterial function. Adolescence is associated with an influx of sex-specific hormones that may exert divergent effects on endothelial function, but whether training adaptations interact with biological maturation to produce a 'youth athlete's artery' has not been explored. We investigated the influence of exercise training-status on endothelium-dependent arterial function during childhood and adolescence. Brachial artery flow mediated dilation (FMD) was assessed in n=102 exercise-trained (males: n=25, females: n=29) and untrained (males: n=23, females: n=25) youths, characterised as pre- (males: n=25, females: n=26) or post- (males: n=23, females: n=28) predicted age at peak height velocity (PHV). Baseline brachial artery diameter was larger in post- compared to pre-PHV youths (P≤0.001), males compared to females (P≤0.001), and trained compared to untrained youths (3.26 ± 0.51mm vs 3.11 ± 0.42mm; P=0.041). Brachial FMD was similar in pre- and post-PHV youths (P=0.298), and males and females (P=0.946). However, exercise trained youths demonstrated higher FMD when compared to untrained counterparts (5.3 ± 3.3% vs 3.0 ± 2.6%; P≤0.001). Furthermore, brachial artery diameter (r2=0.142; P=0.007 vs r2=0.004; P=0.652) and FMD (r2=0.138; P=0.008 vs r2=0.003; P=0.706) were positively associated with cardiorespiratory fitness in post-, but not pre-PHV youths, respectively. Collectively, our data indicate that exercise training is associated with brachial artery remodeling and enhanced endothelial function during youth. However, arterial remodeling and endothelium-dependent function are only associated with elevated cardiorespiratory fitness during later stages of adolescence.

Exercise improves surrogate measures of liver histological response in metabolic dysfunction-associated steatotic liver disease.

BACKGROUND AND AIMS: Exercise is recommended for the management of metabolic dysfunction-associated steatotic liver disease (MASLD), yet effects on liver histology remain unknown, especially without significant weight loss. We aimed to examine changes in surrogate measures of liver histological response with exercise training. METHODS: We conducted a post hoc pooled analysis of three randomised controlled trials (duration: 12-20 weeks) comparing aerobic exercise interventions with controls. The primary outcome measure was a ≥30% relative reduction in (MRI-measured) liver fat, as a surrogate measure of liver histological response (the threshold necessary for fibrosis improvement). Secondary outcome measures were changes in other biomarkers of liver fibrosis, anthropometry, body composition and aerobic fitness. RESULTS: Eighty-eight adults (exercise: 54, control: 34; male: 67%) were included with mean (SD) age 51 (11) years and body mass index 33.3 (5.2) kg/m2. Following the intervention, exercise had ~5-fold (OR [95%CI]: 4.86 [1.72, 13.8], p = .002) greater odds of ≥30% relative reduction in MRI-measured liver fat compared with control. This paralleled the improvements in anthropometry (waist and hip circumference reduction), body composition (body fat, visceral and subcutaneous adipose tissue) and aerobic fitness (V̇O2peak, ventilatory threshold and exercise capacity). Importantly, these effects were independent of clinically significant body weight loss (<3% body weight). CONCLUSION: Exercise training led to clinically meaningful improvements in surrogate serum- and imaging-based measures of liver histological change, without clinically meaningful body weight reduction. These data reinforce the weight-neutral benefit of exercise training and suggest that aerobic training may improve liver fibrosis in patients with MASLD.

Post exercise hot water immersion and hot water immersion in isolation enhance vascular, blood marker, and perceptual responses when compared to exercise alone.

Exercise and passive heating induce some similar vascular hemodynamic, circulating blood marker, and perceptual responses. However, it remains unknown whether post exercise hot water immersion can synergise exercise derived responses and if they differ from hot water immersion alone. This study investigated the acute responses to post moderate-intensity exercise hot water immersion (EX+HWI) when compared to exercise (EX+REST) and hot water immersion (HWI+HWI) alone. Sixteen physically inactive middle-aged adults (nine males and seven females) completed a randomized cross-over counterbalanced design. Each condition consisted of two 30-min bouts separated by 10 min of rest. Cycling was set at a power output equivalent to 50% V̇o2 peak . Water temperature was controlled at 40°C up to the mid sternum with arms not submerged. Venous blood samples and artery ultrasound scans were assessed at 0 (baseline), 30 (immediately post stressor one), 70 (immediately post stressor two), and 100 min (recovery). Additional physiological and perceptual measures were assessed at 10-min intervals. Brachial and superficial femoral artery shear rates were higher after EX+HWI and HWI+HWI when compared with EX+REST (p < 0.001). Plasma nitrite was higher immediately following EX+HWI and HWI+HWI than EX+REST (p < 0.01). Serum interleukin-6 was higher immediately after EX+HWI compared to EX+REST (p = 0.046). Serum cortisol was lower at 30 min in the HWI+HWI condition in contrast to EX+REST (p = 0.026). EX+HWI and HWI+HWI were more enjoyable than EX+REST (p < 0.05). Irrespective of whether hot water immersion proceeded exercise or heating, hot water immersion enhanced vascular and blood marker responses, while also being more enjoyable than exercise alone.

The effect of underwater massage during hot water immersion on acute cardiovascular and mood responses.

PURPOSE: There is emerging evidence that demonstrates the health benefits of hot water immersion including improvements to cardiovascular health and reductions in stress and anxiety. Many commercially available hot tubs offer underwater massage systems which purport to enhance many benefits of hot water immersion, however, these claims have yet to be studied. METHODS: Twenty participants (4 females) completed three, 30-min sessions of hot-water immersion (beginning at 39 °C) in a crossover randomized design: with air massage (Air Jet), water massage (Hydro Jet) or no massage (Control). Cardiovascular responses comprising; heart rate, blood pressure and superficial femoral artery blood flow and shear rate were measured. State trait anxiety, basic affect, and salivary cortisol were recorded before and after each trial. Data were analysed using a mixed effects model. RESULTS: Post immersion, heart rate increased (Δ31bpm, P < 0.001, d = 1.38), mean arterial blood pressure decreased (Δ16 mmHg, P < 0.001, d = -0.66), with no difference between conditions. Blood flow and mean shear rate increased following immersion (P < 0.001, Δ362 ml/min, d = 1.20 and Δ108 s-1, d = 1.00), but these increases were blunted in the Air Jet condition (P < 0.001,Δ171 ml/min, d = 0.43 and Δ52 s-1, d = 0.52). Anxiety and salivary cortisol were reduced (P = 0.003, d = -0.20, P = 0.014, d = -0.11), but did not vary between conditions. Enjoyment did not vary between conditions. CONCLUSION: These data demonstrate positive acute responses to hot water immersion on markers of cardiovascular function, anxiety, and stress. There was no additional benefit of water-based massage, while air-based massage blunted some positive vascular responses due to lower heat conservation of the water.

Neurovascular coupling and cerebrovascular hemodynamics are modified by exercise training status at different stages of maturation during youth.

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 (PCAv and MCAv) and pulsatility index (PCAPI and MCAPI) were assessed via transcranial Doppler ultrasound at rest and during visual NVC stimuli. N = 121 exercise-trained (males, n = 32; females, n = 32) and untrained (males, n = 28; females, n = 29) participants were characterized as pre (males, n = 33; females, n = 29)- or post (males, n = 27; females, n = 32)-peak height velocity (PHV). Exercise-trained youth demonstrated higher resting MCAv (P = 0.010). Maturity and training status did not affect the ΔPCAv and ΔMCAv during NVC. However, pre-PHV untrained males (19.4 ± 13.5 vs. 6.8 ± 6.0%; P ≤ 0.001) and females (19.3 ± 10.8 vs. 6.4 ± 7.1%; P ≤ 0.001) had a higher ΔPCAPI during NVC than post-PHV untrained counterparts, whereas the ΔPCAPI was similar in pre- and post-PHV trained youth. Pre-PHV untrained males (19.4 ± 13.5 vs. 7.9 ± 6.0%; P ≤ 0.001) and females (19.3 ± 10.8 vs. 11.1 ± 7.3%; P = 0.016) also had a larger ΔPCAPI than their pre-PHV trained counterparts during NVC, but the ΔPCAPI 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.NEW & NOTEWORTHY 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.

The effect of age and mitigation strategies during hot water immersion on orthostatic intolerance and thermal stress.

NEW FINDINGS: What is the central question of this study? The aim was to characterize adverse responses to whole-body hot water immersion and to investigate practical strategies to mitigate these effects. What is the main finding and its importance? Whole-body hot water immersion induced transient orthostatic hypotension and impaired postural control, which recovered to baseline within 10 min. Hot water immersion was well tolerated by middle-aged adults, but younger adults suffered from a greater frequency and severity of dizziness. Cooling the face with a fan or not immersing the arms can mitigate some of these adverse responses in younger adults. ABSTRACT: Hot water immersion improves cardiovascular health and sporting performance, yet its adverse responses are understudied. Thirteen young and 17 middle-aged adults (n = 30) were exposed to 2 × 30 min bouts of whole-body 39°C water immersion. Young adults also completed cooling mitigation strategies in a randomized cross-over design. Orthostatic intolerance and selected physiological, perceptual, postural and cognitive responses were assessed. Orthostatic hypotension occurred in 94% of middle-aged adults and 77% of young adults. Young adults exhibited greater dizziness upon standing (young subjects, 3 out of 10 arbitrary units (AU) vs. middle-aged subjects, 2 out of 10 AU), with four terminating the protocol early owing to dizziness or discomfort. Despite middle-aged adults being largely asymptomatic, both age groups had transient impairments in postural sway after immersion (P < 0.05), but no change in cognitive function (P = 0.58). Middle-aged adults reported lower thermal sensation, higher thermal comfort, and higher basic affect than young adults (all P < 0.01). Cooling mitigation trials had 100% completion rates, with improvements in sit-to-stand dizziness (P < 0.01, arms in, 3 out of 10 AU vs. arms out, 2 out of 10 AU vs. fan, 4 out 10 AU), lower thermal sensation (P = 0.04), higher thermal comfort (P < 0.01) and higher basic affect (P = 0.02). Middle-aged adults were predominantly asymptomatic, and cooling strategies prevented severe dizziness and thermal intolerance in younger adults.

Cerebral blood flow and cerebrovascular reactivity are modified by maturational stage and exercise training status during youth.

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. ABSTRACT: Global cerebral blood flow (gCBF) and cerebrovascular reactivity to hypercapnia ( CV R C O 2 ${\mathrm{CV}}{{\mathrm{R}}_{{\mathrm{C}}{{\mathrm{O}}_{\mathrm{2}}}}}$ ) 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 CV R C O 2 ${\mathrm{CV}}{{\mathrm{R}}_{{\mathrm{C}}{{\mathrm{O}}_{\mathrm{2}}}}}$ is currently unknown. Therefore, we used duplex ultrasound to assess gCBF and CV R C O 2 ${\mathrm{CV}}{{\mathrm{R}}_{{\mathrm{C}}{{\mathrm{O}}_{\mathrm{2}}}}}$ 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 CV R C O 2 ${\mathrm{CV}}{{\mathrm{R}}_{{\mathrm{C}}{{\mathrm{O}}_{\mathrm{2}}}}}$ . Data are reported as group means (SD). Pre-PHV youth demonstrated elevated gCBF and slower CV R C O 2 ${\mathrm{CV}}{{\mathrm{R}}_{{\mathrm{C}}{{\mathrm{O}}_{\mathrm{2}}}}}$ 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, CV R C O 2 ${\mathrm{CV}}{{\mathrm{R}}_{{\mathrm{C}}{{\mathrm{O}}_{\mathrm{2}}}}}$ 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 CV R C O 2 ${\mathrm{CV}}{{\mathrm{R}}_{{\mathrm{C}}{{\mathrm{O}}_{\mathrm{2}}}}}$ 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.

The Ultrasound Window Into Vascular Ageing: A Technology Review by the VascAgeNet COST Action.

Non-invasive ultrasound (US) imaging enables the assessment of the properties of superficial blood vessels. Various modes can be used for vascular characteristics analysis, ranging from radiofrequency (RF) data, Doppler- and standard B/M-mode imaging, to more recent ultra-high frequency and ultrafast techniques. The aim of the present work was to provide an overview of the current state-of-the-art non-invasive US technologies and corresponding vascular ageing characteristics from a technological perspective. Following an introduction about the basic concepts of the US technique, the characteristics considered in this review are clustered into: 1) vessel wall structure; 2) dynamic elastic properties, and 3) reactive vessel properties. The overview shows that ultrasound is a versatile, non-invasive, and safe imaging technique that can be adopted for obtaining information about function, structure, and reactivity in superficial arteries. The most suitable setting for a specific application must be selected according to spatial and temporal resolution requirements. The usefulness of standardization in the validation process and performance metric adoption emerges. Computer-based techniques should always be preferred to manual measures, as long as the algorithms and learning procedures are transparent and well described, and the performance leads to better results. Identification of a minimal clinically important difference is a crucial point for drawing conclusions regarding robustness of the techniques and for the translation into practice of any biomarker.

Evidence of region-specific right ventricular functional adaptation in endurance-trained men in response to an acute volume infusion.

NEW FINDINGS: What is the central question of this study? Endurance athletes demonstrate altered regional right ventricular (RV) wall mechanics, characterized by lower basal deformation, in comparison to non-athletic control subjects at rest. We hypothesized that regional adaptations at the RV base reflect an enhanced functional reserve capacity in response to haemodynamic volume loading. What is the main finding and its importance? Free wall RV longitudinal strain is elevated in response to acute volume loading in both endurance athletes and control subjects. However, the RV basal segment longitudinal strain response to acute volume infusion is greater in endurance athletes. Our findings suggest that training-induced cardiac remodelling might involve region-specific adaptation in the RV functional response to volume manipulation. ABSTRACT: Eccentric remodelling of the right ventricle (RV) in response to increased blood volume and repetitive haemodynamic load during endurance exercise is well established. Structural remodelling is accompanied by decreased deformation at the base of the RV free wall, which might reflect an enhanced functional reserve capacity in response to haemodynamic perturbation. Therefore, in this study we examined the impact of acute blood volume expansion on RV wall mechanics in 16 young endurance-trained men (aged 24 ± 3 years) and 13 non-athletic male control subjects (aged 27 ± 5 years). Conventional echocardiographic parameters and the longitudinal strain and strain rate were quantified at the basal and apical levels of the RV free wall. Measurements were obtained at rest and after 7 ml/kg i.v. Gelofusine infusion, with and without a passive leg raise. After infusion, blood volume increased by 12 ± 4 and 14 ± 5% in endurance-trained individuals versus control subjects, respectively (P = 0.264). Both endurance-trained individuals (8 ± 10%) and control subjects (7 ± 9%) experienced an increase in free wall strain from baseline, which was also similar following leg raise (7 ± 10 and 6 ± 10%, respectively; P = 0.464). However, infusion evoked a greater increase in basal longitudinal strain in endurance-trained versus control subjects (16 ± 14 vs. 6 ± 11%; P = 0.048), which persisted after leg raise (16 ± 18 vs. 3 ± 11%; P = 0.032). Apical longitudinal strain and RV free wall strain rates were not different between groups and remained unchanged after infusion across all segments. Endurance training results in a greater contribution of longitudinal myocardial deformation at the base of the RV in response to a haemodynamic volume challenge, which might reflect a greater region-specific functional reserve capacity.

Aortic haemodynamics: the effects of habitual endurance exercise, age and muscle sympathetic vasomotor outflow in healthy men.

PURPOSE: We determined the effect of habitual endurance exercise and age on aortic pulse wave velocity (aPWV), augmentation pressure (AP) and systolic blood pressure (aSBP), with statistical adjustments of aPWV and AP for heart rate and aortic mean arterial pressure, when appropriate. Furthermore, we assessed whether muscle sympathetic nerve activity (MSNA) correlates with AP in young and middle-aged men. METHODS: Aortic PWV, AP, aortic blood pressure (applanation tonometry; SphygmoCor) and MSNA (peroneal microneurography) were recorded in 46 normotensive men who were either young or middle-aged and endurance-trained runners or recreationally active nonrunners (10 nonrunners and 13 runners within each age-group). Between-group differences and relationships between variables were assessed via ANOVA/ANCOVA and Pearson product-moment correlation coefficients, respectively. RESULTS: Adjusted aPWV and adjusted AP were similar between runners and nonrunners in both age groups (all, P > 0.05), but higher with age (all, P < 0.001), with a greater effect size for the age-related difference in AP in runners (Hedges' g, 3.6 vs 2.6). aSBP was lower in young (P = 0.009; g = 2.6), but not middle-aged (P = 0.341; g = 1.1), runners compared to nonrunners. MSNA burst frequency did not correlate with AP in either age group (young: r = 0.00, P = 0.994; middle-aged: r = - 0.11, P = 0.604). CONCLUSION: There is an age-dependent effect of habitual exercise on aortic haemodynamics, with lower aSBP in young runners compared to nonrunners only. Statistical adjustment of aPWV and AP markedly influenced the outcomes of this study, highlighting the importance of performing these analyses. Further, peripheral sympathetic vasomotor outflow and AP were not correlated in young or middle-aged normotensive men.

The influence of barosensory vessel mechanics on the vascular sympathetic baroreflex: insights into aging and blood pressure homeostasis.

Changes in the arterial baroreflex arc contribute to elevated sympathetic outflow and altered reflex control of blood pressure with human aging. Using ultrasound and sympathetic microneurography (muscle sympathetic nerve activity, MSNA) we investigated the relationships between aortic and carotid artery wall tension (indices of baroreceptor activation) and the vascular sympathetic baroreflex operating point (OP; MSNA burst incidence) in healthy, normotensive young (n = 27, 23 ± 3 yr) and middle-aged men (n = 22, 55 ± 4 yr). In young men, the OP was positively related to the magnitude and rate of unloading and time spent unloaded in the aortic artery (r = 0.56, 0.65, and 0.51, P = 0.02, 0.003, and 0.03), but not related to the magnitude or rate of unloading or time spent unloaded in the carotid artery (r = -0.32, -0.07, and 0.06, P = 0.25, 0.81, and 0.85). In contrast, in middle-aged men, the OP was not related to either the magnitude or rate of unloading or time spent unloaded in the aortic (r = 0.22, 0.21, and 0.27, P = 0.41, 0.43, and 0.31) or carotid artery (r = 0.06, 0.28, and -0.01; P = 0.48, 0.25, and 0.98). In conclusion, in young men, aortic unloading mechanics may play a role in determining the vascular sympathetic baroreflex OP. In contrast, in middle-aged men, barosensory vessel unloading mechanics do not appear to determine the vascular sympathetic baroreflex OP and, therefore, do not contribute to age-related arterial baroreflex resetting and increased resting MSNA.NEW & NOTEWORTHY We assessed the influence of barosensory vessel mechanics (magnitude and rate of unloading and time spent unloaded) as a surrogate for baroreceptor unloading. In young men, aortic unloading mechanics are important in regulating the operating point of the vascular sympathetic baroreflex, whereas in middle-aged men, these arterial mechanics do not influence this operating point. The age-related increase in resting muscle sympathetic nerve activity does not appear to be driven by altered baroreceptor input from stiffer barosensory vessels.

Stimulus-specific functional remodeling of the left ventricle in endurance and resistance-trained men.

Left ventricular (LV) structural remodeling following athletic training has been evidenced through training-specific changes in wall thickness and geometry. Whether the LV response to changes in hemodynamic load also adapts in a training-specific manner is unknown. Using echocardiography, we examined LV responses of endurance-trained (n = 15), resistance-trained (n = 14), and nonathletic men (n = 13) to 1) 20, 40, and 60% one repetition-maximum (1RM), leg-press exercise and 2) intravascular Gelofusine infusion (7 mL/kg) with passive leg raise. While resting heart rate was lower in endurance-trained participants versus controls (P = 0.001), blood pressure was similar between groups. Endurance-trained individuals had lower wall thickness but greater LV mass relative to body surface area versus controls, with no difference between resistance-trained individuals and controls. Leg press evoked a similar increase in blood pressure; however, resistance-trained participants preserved stroke volume (SV; -3 ± 8%) versus controls at 60% 1RM (-15 ± 7%, P = 0.001). While the maintenance of SV was related to the change in longitudinal strain across all groups (R = 0.537; P = 0.007), time-to-peak strain was maintained in resistance-trained but delayed in endurance-trained individuals (1 vs. 12% delay; P = 0.021). Volume infusion caused a similar increase in end-diastolic volume (EDV) and SV across groups, but leg raise further increased EDV only in endurance-trained individuals (5 ± 5 to 8 ± 5%; P = 0.018). Correlation analysis revealed a relationship between SV and longitudinal strain following infusion and leg raise (R = 0.334, P = 0.054); however, we observed no between-group differences in longitudinal myocardial mechanics. In conclusion, resistance-trained individuals better maintained SV during pressure loading, whereas endurance-trained individuals demonstrated greater EDV reserve during volume loading. These data provide novel evidence of training-specific LV functional remodeling.NEW & NOTEWORTHY Training-specific functional remodeling of the LV in response to different loading conditions has been recently suggested, but not experimentally tested in the same group of individuals. Our data provide novel evidence of a dichotomous, training-specific LV adaptive response to hemodynamic pressure or volume loading.

The influence of habitual endurance exercise on carotid artery strain and strain rate in young and middle-aged men.

NEW FINDINGS: What is the central question of this study? Carotid artery peak circumferential strain (PCS) and strain rate attenuate with age, but appear to be modulated by cardiorespiratory fitness status in young males. However, the relationship between habitual endurance exercise (running) and these parameters has not been studied in young and middle-aged men. What is the main finding and its importance? Young and middle-aged runners exhibited elevated PCS and systolic strain rate (S-SR) compared with non-runners, but habitual running did not influence diastolic strain rate (D-SR). Habitual exercise is associated with comparable improvements in carotid strain parameters in young and middle-aged men, but the age-related decline in PCS and S-SR might be more amenable to habitual endurance exercise than D-SR. ABSTRACT: Central arterial stiffness is an independent predictor of cardiovascular risk that can be modified by exercise training. However, conventional local measures of carotid artery stiffness display conflicting responses to habitual endurance exercise in young and older adults. Two-dimensional (2D)-Strain imaging of the common carotid artery (CCA) quantifies circumferential deformation (strain) of the arterial wall across the cardiac cycle, which is more sensitive at detecting age-related alterations in CCA stiffness than conventional methods. Therefore, the study was designed to examine the relationship between habitual endurance exercise (running) and CCA 2D-Strain parameters in young and middle-aged men. Short-axis ultrasound images of the CCA were obtained from 13 young non-runners [23 years of age (95% confidence interval: 21, 26 years of age)], 19 young runners [24 (22, 26) years of age], 13 middle-aged non-runners [54 (52, 56) years of age] and 19 middle-aged runners [56 (54, 58) years of age]. Images were analysed for peak circumferential strain (PCS; magnitude of deformation) and systolic and diastolic strain rates (S-SR and D-SR; deformation velocity), and group differences were examined via two-way ANOVA. PCS, S-SR and D-SR were attenuated in middle-aged men compared with young men (all P ≤ 0.001). PCS and S-SR were elevated in young and middle-aged runners when compared with non-runners (P = 0.002 and P = 0.009, respectively), but no age × training status interaction was observed. In contrast, there was no influence of habitual running on D-SR. Habitual exercise is associated with comparable improvements in CCA 2D-Strain parameters in young and middle-aged men, but the age-related decline in PCS and S-SR might be more amenable to habitual endurance exercise than D-SR.

Upward resetting of the vascular sympathetic baroreflex in middle-aged male runners.

This study focused on the influence of habitual endurance exercise training (i.e., committed runner or nonrunner) on the regulation of muscle sympathetic nerve activity (MSNA) and arterial pressure in middle-aged (50 to 63 yr, n = 23) and younger (19 to 30 yr; n = 23) normotensive men. Hemodynamic and neurophysiological assessments were performed at rest. Indices of vascular sympathetic baroreflex function were determined from the relationship between spontaneous changes in diastolic blood pressure (DBP) and MSNA. Large vessel arterial stiffness and left ventricular stroke volume also were measured. Paired comparisons were performed within each age category. Mean arterial pressure and basal MSNA bursts/min were not different between age-matched runners and nonrunners. However, MSNA bursts/100 heartbeats, an index of baroreflex regulation of MSNA (vascular sympathetic baroreflex operating point), was higher for middle-aged runners (P = 0.006), whereas this was not different between young runners and nonrunners. The slope of the DBP-MSNA relationship (vascular sympathetic baroreflex gain) was not different between groups in either age category. Aortic pulse wave velocity was lower for runners of both age categories (P < 0.03), although carotid ß-stiffness was lower only for middle-aged runners (P = 0.04). For runners of both age categories, stroke volume was larger, whereas heart rate was lower (both P < 0.01). In conclusion, we suggest that neural remodeling and upward setting of the vascular sympathetic baroreflex compensates for cardiovascular adaptations after many years committed to endurance exercise training, presumably to maintain arterial blood pressure stability. NEW & NOTEWORTHY Exercise training reduces muscle sympathetic burst activity in disease; this is often extrapolated to infer a similar effect in health. We demonstrate that burst frequency of middle-aged and younger men committed to endurance training is not different compared with age-matched casual exercisers. Notably, well-trained, middle-aged runners display similar arterial pressure but higher sympathetic burst occurrence than untrained peers. We suggest that homeostatic plasticity and upward setting of the vascular sympathetic baroreflex maintains arterial pressure stability following years of training.

Carotid artery wall mechanics in young males with high cardiorespiratory fitness.

NEW FINDINGS: What is the central question of this study? Common carotid artery (CCA) two-dimensional strain imaging detects intrinsic arterial wall properties beyond conventional measures of arterial stiffness, but the effect of cardiorespiratory fitness on two-dimensional strain-derived indices of CCA stiffness is unknown. What is the main finding and its importance? Two-dimensional strain imaging of the CCA revealed greater peak circumferential strain and systolic strain rate in highly fit men compared with their less fit counterparts. Altered CCA wall mechanics might reflect intrinsic training-induced adaptations that help to buffer the increase in pulse pressure and stroke volume during exercise. ABSTRACT: The influence of cardiorespiratory fitness on arterial stiffness in young adults remains equivocal. Beyond conventional measures of arterial stiffness, two-dimensional strain imaging of the common carotid artery (CCA) provides new information related to the intrinsic properties of the arterial wall. Therefore, the aim of this study was to assess the effect of cardiorespiratory fitness on both conventional indices of CCA stiffness and two-dimensional strain parameters, at rest and after a bout of aerobic exercise in young, healthy men. Short-axis ultrasound images of the CCA were recorded in 34 healthy men {22 years old [95% confidence interval (CI), 19, 22]} before and immediately after 5 min of aerobic exercise (40% of maximal oxygen consumption). Images were analysed for arterial diameter, peak circumferential strain (PCS) and peak systolic and diastolic strain rates (S-SR and D-SR). Heart rate, systolic and diastolic blood pressure were simultaneously assessed, and Peterson's elastic modulus (Ep ) and ß-stiffness (ß1 ) were calculated. Participants were separated post hoc into moderate- and high-fitness groups [maximal oxygen consumption, 48.9 (95% CI, 44.7, 53.2) versus 65.6 ml kg-1  min-1 (95% CI, 63.1, 68.1), respectively; P < 0.001]. The Ep and ß1 were similar between groups at baseline (P > 0.13) but were elevated in the moderate-fitness group postexercise (P < 0.04). The PCS and S-SR were elevated in the high-fitness group at both time points [3.0% (95% CI, 1.2, 4.9), P = 0.002, and 0.401 s-1 (95% CI, 0.085, 0.72), P = 0.02, respectively]. No group differences were observed in CCA heart rate, systolic or diastolic blood pressure or D-SR throughout the protocol (P > 0.05). Highly fit individuals exhibit elevated CCA, PCS and S-SR, which might reflect training-induced adaptations that help to buffer the increase in pulse pressure and stroke volume during exercise.

Dissociation between exercise-induced reduction in liver fat and changes in hepatic and peripheral glucose homoeostasis in obese patients with non-alcoholic fatty liver disease.

Non-alcoholic fatty liver disease (NAFLD) is associated with multi-organ (hepatic, skeletal muscle, adipose tissue) insulin resistance (IR). Exercise is an effective treatment for lowering liver fat but its effect on IR in NAFLD is unknown. We aimed to determine whether supervised exercise in NAFLD would reduce liver fat and improve hepatic and peripheral (skeletal muscle and adipose tissue) insulin sensitivity. Sixty nine NAFLD patients were randomized to 16 weeks exercise supervision (n=38) or counselling (n=31) without dietary modification. All participants underwent MRI/spectroscopy to assess changes in body fat and in liver and skeletal muscle triglyceride, before and following exercise/counselling. To quantify changes in hepatic and peripheral insulin sensitivity, a pre-determined subset (n=12 per group) underwent a two-stage hyperinsulinaemic euglycaemic clamp pre- and post-intervention. Results are shown as mean [95% confidence interval (CI)]. Fifty participants (30 exercise, 20 counselling), 51 years (IQR 40, 56), body mass index (BMI) 31 kg/m(2) (IQR 29, 35) with baseline liver fat/water % of 18.8% (IQR 10.7, 34.6) completed the study (12/12 exercise and 7/12 counselling completed the clamp studies). Supervised exercise mediated a greater reduction in liver fat/water percentage than counselling [Δ mean change 4.7% (0.01, 9.4); P<0.05], which correlated with the change in cardiorespiratory fitness (r=-0.34, P=0.0173). With exercise, peripheral insulin sensitivity significantly increased (following high-dose insulin) despite no significant change in hepatic glucose production (HGP; following low-dose insulin); no changes were observed in the control group. Although supervised exercise effectively reduced liver fat, improving peripheral IR in NAFLD, the reduction in liver fat was insufficient to improve hepatic IR.

Exercise training reverses endothelial dysfunction in nonalcoholic fatty liver disease.

Nonalcoholic fatty liver disease (NAFLD) is an independent risk factor for cardiovascular disease (CVD). Endothelial dysfunction is an early manifestation of atherosclerosis and an important prognostic marker for future cardiovascular events. The aim of this study was twofold: to examine 1) the association between liver fat, visceral adipose tissue (VAT), and endothelial dysfunction in obese NAFLD patients and 2) the impact of supervised exercise training on this vascular defect. Brachial artery endothelial function was assessed by flow-mediated dilatation (FMD) in 34 obese NAFLD patients and 20 obese controls of similar age and cardiorespiratory fitness [peak oxygen uptake (V̇o2 peak)] (48 ± 2 vs. 47 ± 2 yr; 27 ± 1 vs. 26 ± 2 ml·kg−1·min−1−1). Magnetic resonance imaging and spectroscopy quantified abdominal and liver fat, respectively. Twenty-one NAFLD patients completed either 16 wk of supervised moderate-intensity exercise training (n = 13) or conventional care (n = 8). Differences between NAFLD and controls were compared using independent t-tests and effects of interventions by analysis of covariance. NAFLD patients had higher liver fat [11.6% (95% CI = 7.4, 18.1), P < 0.0005] and VAT [1.6 liters (95% CI = 1.2, 2.0), P < 0.0001] than controls and exhibited impaired FMD compared with controls [−3.6% (95% CI = −4.9, −2.2), P < 0.0001]. FMD was inversely correlated with VAT (r = −0.54, P = 0.001) in NAFLD, although the impairment in FMD remained following covariate adjustment for VAT [3.1% (95% CI = 1.8, 4.5), P < 0.001]. Exercise training, but not conventional care, significantly improved V̇o2 peak [9.1 ml·kg−1·min−1 (95% CI = 4.1, 14.1); P = 0.001] and FMD [3.6% (95% CI = 1.6, 5.7), P = 0.002]. Endothelial dysfunction in NAFLD cannot be fully explained by excess VAT but can be reversed with exercise training; this has potential implications for the primary prevention of CVD in NAFLD.

Cardiovascular responses to water immersion in humans: impact on cerebral perfusion.

Episodic increases in cerebrovascular perfusion and shear stress may have beneficial impacts on endothelial function that improve brain health. We hypothesized that water immersion to the level of the right atrium in humans would increase cerebral perfusion. We continuously measured, in 9 young (means ± SD, 24.6 ± 2.0 yr) healthy men, systemic hemodynamic variables along with blood flows in the common carotid and middle and posterior cerebral arteries during controlled filling and emptying of a water tank to the level of the right atrium. Mean arterial pressure (80 ± 9 vs. 91 ± 12 mmHg, P < 0.05), cardiac output (4.8 ± 0.7 vs. 5.1 ± 0.6 l/min, P < 0.05) and end-tidal carbon dioxide (PetCO2, 39.5 ± 2.0 vs. 44.4 ± 3.5 mmHg, P < 0.05) increased with water immersion, along with middle (59 ± 6 vs. 64 ± 6 cm/s, P < 0.05) and posterior cerebral artery blood flow velocities (41 ± 9 vs. 44 ± 10 cm/s, P < 0.05). These changes were reversed when the tank was emptied. Water immersion is associated with hemodynamic and PetCO2 changes, which increase cerebral blood velocities in humans. This study provides an evidence base for future studies to examine the potential additive effect of exercise in water on improving cerebrovascular health.

Endothelial dysfunction in hyperandrogenic polycystic ovary syndrome is not explained by either obesity or ectopic fat deposition.

PCOS (polycystic ovary syndrome) is associated with IR (insulin resistance), increased visceral fat and NAFLD (non-alcoholic fatty liver disease) all of which may contribute to endothelial dysfunction, an early marker of CVD (cardiovascular disease) risk. Our objective was to examine the relationships between endothelial dysfunction in PCOS, the volume of AT (adipose tissue) compartments and the size of intracellular TAG (triacylglycerol) pools in liver and skeletal muscle. A total of 19 women with PCOS (means±S.D.; 26±6 years, 36±5 kg/m2) and 16 control women (31±8 years, 30±6 kg/m2) were recruited. Endothelial function was assessed in the brachial artery using FMD (flow-mediated dilation). VAT (visceral AT) and abdominal SAT (subcutaneous AT) volume were determined by whole body MRI, and liver and skeletal muscle TAG by 1H-MRS (proton magnetic resonance spectroscopy). Cardiorespiratory fitness and HOMA-IR (homoeostasis model assessment of IR) were also determined. Differences between groups were analysed using independent Student's t tests and ANCOVA (analysis of co-variance). FMD was impaired in PCOS by 4.6% [95% CI (confidence interval), 3.0-7.7; P<0.001], and this difference decreased only slightly to 4.2% (95% CI, 2.4-6.1; P<0.001) when FMD was adjusted for individual differences in visceral and SAT and HOMA-IR. This magnitude of impairment was also similar in lean and obese PCOS women. The results suggest that endothelial dysfunction in PCOS is not explained by body fat distribution or volume. FMD might be a useful independent prognostic tool to assess CVD risk in this population.