Agreement between left and right middle cerebral artery blood velocity responses to incremental and constant work-rate exercise in healthy males and females.

Objective.To quantify the agreement between left and right middle cerebral artery blood velocity (MCAv) responses to incremental and constant work-rate exercise in adults.ApproachSeventeen healthy adults (23.8 ± 2.4 years, 9 females) completed a ramp incremental test to exhaustion on a cycle ergometer, three 6-minute transitions at a moderate-intensity, and three at a heavy-intensity, all on separate days. Bilateral MCAv was measured throughout using transcranial Doppler ultrasonography, with left and right MCAv data analysed separately. Data were analysed at baseline, gas exchange threshold, respiratory compensation point and exhaustion during ramp incremental exercise. MCAv responses to constant work-rate exercise were analysed using a mono-exponential model, to determine time- and amplitude-based kinetic response parameters.Main ResultsLeft and right MCAv responses to incremental and constant work-rate exercise were significantly, strongly and positively correlated (r≥ 0.61,P< 0.01). Coefficient of variation (left versus right) ranged from 7.3%-20.7%, 6.4%-26.2% and 5.9%-22.5% for ramp, moderate and heavy-intensity exercise, respectively. The relative change in MCAv from baseline was higher in the right compared to left MCAv during ramp, moderate and heavy-intensity exercise (allP< 0.05), but the effect sizes were small (d≤ 0.4). Small mean left-right differences were present during ramp incremental exercise at all time-points (<6 cm s-1; <4%), and for all kinetic parameters during moderate and heavy-intensity exercise (<3 cm s-1, <3%, <4 s).SignificanceThese findings demonstrate similarities between left and right MCAv responses to incremental and constant-work rate exercise in adults on a group-level, but also highlight individual variation in the agreement between left and right MCAv exercise responses.

The acute effect of exercise intensity on peripheral and cerebral vascular function in healthy adults.

The acute effect of exercise intensity on cerebrovascular reactivity and whether this mirrors changes in peripheral vascular function have not been investigated. The aim of this study was to explore the acute effect of exercise intensity on cerebrovascular reactivity (CVR) and peripheral vascular function in healthy young adults (n = 10, 6 females, 22.7 ± 3.5 yr). Participants completed four experimental conditions on separate days: high-intensity interval exercise (HIIE) with intervals performed at 75% maximal oxygen uptake (V̇o2max; HIIE1), HIIE with intervals performed at 90% V̇o2max (HIIE2), continuous moderate-intensity exercise (MIE) at 60% V̇o2max and a sedentary control condition (CON). All exercise conditions were completed on a cycle ergometer and matched for time (30 min) and average intensity (60% V̇o2max). Brachial artery flow-mediated dilation (FMD) and CVR of the middle cerebral artery were measured before exercise, and 1- and 3-h after exercise. CVR was assessed using transcranial Doppler ultrasonography to both hypercapnia (6% carbon dioxide breathing) and hypocapnia (hyperventilation). FMD was significantly elevated above baseline 1 and 3 h following both HIIE conditions (P < 0.05), but FMD was unchanged following the MIE and CON trials (P > 0.33). CVR to both hypercapnia and hypocapnia, and when expressed across the end-tidal CO2 range, was unchanged in all conditions, at all time points (all P > 0.14). In conclusion, these novel findings show that the acute increases in peripheral vascular function following HIIE, compared with MIE, were not mirrored by changes in cerebrovascular reactivity, which was unaltered following all exercise conditions in healthy young adults.NEW & NOTEWORTHY This is the first study to identify that acute improvements in peripheral vascular function following high-intensity interval exercise are not mirrored by improvements in cerebrovascular reactivity in healthy young adults. High-intensity interval exercise completed at both 75% and 90% V̇o2max increased brachial artery flow-mediated dilation 1 and 3 h following exercise, compared with continuous moderate-intensity exercise and a sedentary control condition. By contrast, cerebrovascular reactivity was unchanged following all four conditions.

The effect of exercise intensity and cardiorespiratory fitness on the kinetic response of middle cerebral artery blood velocity during exercise in healthy adults.

The aim of this study was to compare the kinetic response of middle cerebral artery blood velocity (MCAv) to moderate- and heavy-intensity cycling in adults, and explore the relationship between maximal oxygen uptake (V̇o2max) and MCAv kinetics. Seventeen healthy adults (23.8 ± 2.4 yr, 9 females) completed a ramp incremental test to exhaustion on a cycle ergometer to determine V̇o2max and the gas exchange threshold (GET). Across six separate visits, participants completed three 6-min transitions at a moderate intensity (90% GET) and three at a heavy intensity (40% of the difference between GET and V̇o2max). Bilateral MCAv was measured using transcranial Doppler (TCD) ultrasonography and analyzed using a monoexponential model with a time delay. The time constant (τ) of the MCAv response was not different between moderate- and heavy-intensity cycling (25 ± 10 vs. 26 ± 8 s, P = 0.82), as was the time delay (29 ± 11 vs. 29 ± 10 s, P = 0.95). The amplitude of the exponential increase in MCAv from baseline was greater during heavy-intensity cycling (23.9 ± 10.0 cm·s-1, 34.1 ± 14.4%) compared with moderate-intensity cycling (12.7 ± 4.4 cm·s-1, 18.7 ± 7.5%; P < 0.01). Following the exponential increase, a greater fall in MCAv was observed during heavy-intensity exercise compared with moderate-intensity exercise (9.5 ± 6.9 vs. 2.8 ± 3.8 cm·s-1, P < 0.01). MCAv after 6 min of exercise remained elevated during heavy-intensity exercise compared with moderate-intensity exercise (85.2 ± 9.6 vs. 79.3 ± 7.7 cm·s-1, P ≤ 0.01). V̇o2max was not correlated with MCAv τ or amplitude (r = 0.11-0.26, P > 0.05). These data suggest that the intensity of constant-work rate exercise influences the amplitude, but not time-based, response parameters of MCAv in healthy adults, and found no relationship between cardiorespiratory fitness and MCAv kinetics.NEW & NOTEWORTHY This is the first study to model the MCAv kinetic response to moderate- and heavy-intensity cycling in healthy adults. This study found that the amplitude of the exponential rise in MCAv at exercise onset was greater during heavy-intensity exercise (∼34%) compared with moderate-intensity exercise (∼19%), but the time-based characteristics of the responses were similar between intensities. Higher cardiorespiratory fitness was not associated with a greater or faster MCAv response to moderate- or heavy-intensity exercise.

The role of cardiopulmonary exercise testing in predicting mortality and morbidity in people with congenital heart disease: a systematic review and meta-analysis.

AIMS: The role of cardiopulmonary exercise testing (CPET) in predicting major adverse cardiovascular events (MACE) in people with congenital heart disease (ConHD) is unknown. A systematic review with meta-analysis was conducted to report the associations between CPET parameters and MACE in people with ConHD. METHODS AND RESULTS: Electronic databases were systematically searched on 30 April 2020 for eligible publications. Two authors independently screened publications for inclusion, extracted study data, and performed risk of bias assessment. Primary meta-analysis pooled univariate hazard ratios across studies. A total of 34 studies (18 335 participants; 26.2 ± 10.1 years; 54% ± 16% male) were pooled into a meta-analysis. More than 20 different CPET prognostic factors were reported across 6 ConHD types. Of the 34 studies included in the meta-analysis, 10 (29%), 23 (68%), and 1 (3%) were judged as a low, medium, and high risk of bias, respectively. Primary univariate meta-analysis showed consistent evidence that improved peak and submaximal CPET measures are associated with a reduce risk of MACE. This association was supported by a secondary meta-analysis of multivariate estimates and individual studies that could not be numerically pooled. CONCLUSION: Various maximal and submaximal CPET measures are prognostic of MACE across a variety of ConHD diagnoses. Further well-conducted prospective multicentre cohort studies are needed to confirm these findings.

The within- and between-day reliability of cerebrovascular reactivity using traditional and novel analytical approaches.

NEW FINDINGS: What is the central question of the study? What is the reliability of middle cerebral artery velocity cerebrovascular reactivity (CVR) when using traditional and novel outcomes, as measured by transcranial Doppler? What is the main finding and its importance? Traditional CVR approaches presented acceptable reproducibility but should be expressed as an absolute CVR. Large within- and between-individual differences in the middle cerebral artery velocity response profile support using a dynamic peak, rather than a set time point, for the most reliable interpretation. The study highlights the utility of novel kinetic CVR outcomes, but due to increased variability in time-based metrics, this analysis requires larger sample sizes than traditional methods. ABSTRACT: Cerebrovascular reactivity (CVR) of middle cerebral artery velocity (MCAv) to CO2 is a common method to assess cerebrovascular function. Yet, the approaches used to calculate CVR outcomes vary. The aim of this study was to explore the within- and between-day reliability of traditional CVR outcomes. The second aim was to explore the reliability of novel kinetic-based analyses. Healthy adults (n = 10, 22.3 ± 3.4 years) completed assessments of CVR over 4 min using a fixed fraction of inspired CO2 (6%). This was repeated across four separate visits (between-day), and on one visit measures were repeated 2.5 h later (within-day). No mean biases were present between assessments for traditional CVR metrics, expressed as absolute (cm/s/mmHg) or relative (%/mmHg) outcomes (minute 3, minute 4, peak 1 s, peak 30 s) (between-day: P > 0.14, ηp2 < 0.20; within-day: P > 0.22, d > 0.27). Absolute, rather than relative, CVR yielded the most reproducible parameters (coefficient of variation: 8.1-13.2% vs. 14-83%, respectively). There were significant differences between CVR outcomes (P < 0.001, ηp2 > 0.89) dependent on the time point used to determine CVR, as a steady state MCAv response was rarely observed. Furthermore, the MCAv response was not reproducible within an individual (κ = 0.15, P = 0.09). No mean differences were present for novel kinetic outcomes (amplitude, time-delay, time constant) (between-day: P > 0.05, d < 0.33; within-day: P > 0.38, d < 0.25). The results support the need for standardisation and indicate CVR should be defined as a dynamic peak, rather than a set time point for increased reliability. For novel kinetic outcomes variability was greater (CV: 8.7-120.9%) due to the nature of time-based metrics.

Differences in cerebrovascular regulation and ventilatory responses during ramp incremental cycling in children, adolescents, and adults.

Regulation of cerebral blood flow during exercise in youth is poorly understood. This study investigated the cerebrovascular and ventilatory responses to a ramp incremental cycle test to exhaustion in 14 children (means ± SD age: 9.4 ± 0.9 yr), 14 adolescents (12.4 ± 0.4 yr), and 19 adults (23.4 ± 2.5 yr). Middle cerebral artery blood velocity (MCAv), partial pressure of end-tidal CO2 ([Formula: see text]), and ventilatory parameters were analyzed at baseline, gas exchange threshold (GET), respiratory compensation point (RCP), and exhaustion. The increase in minute ventilation relative to CO2 production during exercise was also calculated (V̇e/V̇co2 slope). Relative change from baseline (Δ%) in MCAv was lower in children, compared with adolescents and adults at GET [15 ± 10% vs. 26 ± 14%, and 24 ± 10%, respectively, P ≤ 0.03, effect size (d) = 0.9] and RCP (13 ± 11% vs. 24 ± 16% and 27 ± 15%, respectively, P ≤ 0.05, d ≥ 0.8). Δ%MCAv was similar in adults and adolescents at all intensities and similar in all groups at exhaustion. The magnitude of the V̇E/V̇co2 slope was negatively associated with Δ%MCAv at GET and RCP across all participants (P ≤ 0.01, r = -0.37 to -0.48). Δ%[Formula: see text] was smaller in children and adolescents compared with adults at GET and RCP (P ≤ 0.05, d ≥ 0.6). In children, Δ%[Formula: see text] and Δ%MCAv were not associated from baseline-GET (r¯ = 0.14) and were moderately associated from RCP-exhaustion (r¯ = 0.49). These relationships strengthened with increasing age and were stronger in adolescents (baseline-GET: r¯ = 0.47, RCP-exhaustion: r¯ = 0.62) and adults (baseline-GET: r¯ = 0.66, RCP-exhaustion: r¯ = 0.78). These findings provide the first evidence on the development of the regulatory role of [Formula: see text] on MCAv during exercise in children, adolescents, and adults.NEW & NOTEWORTHY This is the first study to observe similar increases in cerebral blood flow during incremental exercise in adolescents and adults. Increases in cerebral blood flow during exercise were smaller in children compared with adolescents and adults and were associated with a greater V̇E/V̇co2 slope. This study also provides the first evidence on the progressive development of the regulatory role of end-tidal CO2 on cerebral blood flow during exercise during the transition from childhood to adulthood.

The acute and postprandial effects of sugar moiety on vascular and metabolic health outcomes in adolescents.

This study explored the cardiometabolic responses to sugar moieties acutely, and following a subsequent mixed meal tolerance test (MMTT). Twenty-one healthy adolescents (N = 10 female, 14.3 ± 0.4 years) completed 3 experimental and 1 control condition, in a counterbalanced order. These consisted of different drinks to compare the effect of 300 mL of water (control), or 300 mL of water mixed with 60 g of glucose, fructose or sucrose, on vascular function (flow-mediated dilation (FMD), microvascular reactivity (total hyperaemic response; TRH), and cerebrovascular reactivity (CVR)), and blood samples for uric acid, glucose, triglycerides and lactate concentrations. FMD increased 1 h after glucose and sucrose (P < 0.001, ES ≥ 0.92) but was unchanged following fructose and water (P ≥ 0.19, ES ≥ 0.09). CVR and TRH were unchanged 1 h following all conditions (P > 0.57, effect size (ES) > 0.02). Following the MMTT, FMD was impaired in all conditions (P < 0.001, ES > 0.40) with no differences between conditions (P > 0.13, ES < 0.39). Microvascular TRH was increased in all conditions (P = 0.001, ES = 0.88), and CVR was preserved in all conditions after MMTT (P = 0.87, ES = 0.02). Blood uric acid concentration was elevated following fructose consumption and the MMTT (P < 0.01, ES > 0.40). Consumption of a sugar sweetened beverage did not result in vascular dysfunction in healthy adolescents; however, the vascular and metabolic responses were dependent on sugar moiety. Novelty: Glucose consumption acutely increases peripheral vascular function in healthy adolescents. Acute sugar sweetened beverage consumption (sucrose) does not result in adverse vascular outcomes. Elevations in uric acid are observed with fructose consumption, which may have implications over repeated exposure.

The reliability of a breath-hold protocol to determine cerebrovascular reactivity in adolescents.

PURPOSE: Cerebrovascular reactivity (CVR) is impaired in adolescents with cardiovascular disease risk factors. A breath-hold test is a noninvasive method of assessing CVR, yet there are no reliability data of this outcome in youth. This study aimed to assess the reliability of a breath-hold protocol to measure CVR in adolescents. METHODS: Twenty-one 13 to 15 year old adolescents visited the laboratory on two separate occasions, to assess the within-test, within-day and between-day reliability of a breath-hold protocol, consisting of three breath-hold attempts. CVR was defined as the relative increase from baseline in middle cerebral artery mean blood velocity following a maximal breath-hold of up to 30 seconds, quantified via transcranial Doppler ultrasonography. RESULTS: Mean breath-hold duration and CVR were never significantly correlated (r < .31, P > .08). The within-test coefficient of variation for CVR was 15.2%, with no significant differences across breath-holds (P = .88), so the three breath-hold attempts were averaged for subsequent analyses. The within- and between-day coefficients of variation for CVR were 10.8% and 15.3%, respectively. CONCLUSIONS: CVR assessed via a three breath-hold protocol can be reliably measured in adolescents, yielding similar within- and between-day reliability. Analyses revealed that breath-hold length and CVR were unrelated, indicating the commonly reported normalization of CVR to breath-hold duration (breath-hold index) may be unnecessary in youth.

Validity of the Supramaximal Test to Verify Maximal Oxygen Uptake in Children and Adolescents.

Purpose: This study had 2 objectives: (1) to examine whether the validity of the supramaximal verification test for maximal oxygen uptake ( V˙O2max ) differs in children and adolescents when stratified for sex, body mass, and cardiorespiratory fitness and (2) to assess sensitivity and specificity of primary and secondary objective criteria from the incremental test to verify V˙O2max . Methods: In total, 128 children and adolescents (76 male and 52 females; age: 9.3-17.4 y) performed a ramp-incremental test to exhaustion on a cycle ergometer followed by a supramaximal test to verify V˙O2max . Results: Supramaximal tests verified V˙O2max in 88% of participants. Group incremental test peak V˙O2 was greater than the supramaximal test (2.27 [0.65] L·min-1 and 2.17 [0.63] L·min-1; P < .001), although both were correlated (r = .94; P < .001). No differences were found in V˙O2 plateau attainment or supramaximal test verification between sex, body mass, or cardiorespiratory fitness groups (all Ps > .18). Supramaximal test time to exhaustion predicted supramaximal test V˙O2max verification (P = .04). Primary and secondary objective criteria had insufficient sensitivity (7.1%-24.1%) and specificity (50%-100%) to verify V˙O2max . Conclusion: The utility of supramaximal testing to verify V˙O2max is not affected by sex, body mass, or cardiorespiratory fitness status. Supramaximal testing should replace secondary objective criteria to verify V˙O2max .