Exhaustive single-leg exercise has been suggested to reduce time to task failure (Tlim) during subsequent exercise in the contralateral leg by exacerbating central fatigue development. We investigated the influence of acetaminophen (ACT), an analgesic that may blunt central fatigue development, on Tlim during single-leg exercise completed with and without prior fatiguing exercise of the contralateral leg. Fourteen recreationally active men performed single-leg severe-intensity knee-extensor exercise to Tlim on the left (Leg1) and right (Leg2) legs without prior contralateral fatigue and on Leg2 immediately following Leg1 (Leg2-CONTRA). The tests were completed following ingestion of 1-g ACT or maltodextrin [placebo (PL)] capsules. Intramuscular phosphorus-containing metabolites and substrates and muscle activation were assessed using 31P-MRS and electromyography, respectively. Tlim was not different between Leg1ACT and Leg1PL conditions (402 ± 101 vs. 390 ± 106 s, P = 0.11). There was also no difference in Tlim between Leg2ACT-CONTRA and Leg2PL-CONTRA (324 ± 85 vs. 311 ± 92 s, P = 0.10), but Tlim was shorter in Leg2ACT-CONTRA and Leg2PL-CONTRA than in Leg2CON (385 ± 104 s, both P < 0.05). There were no differences in intramuscular phosphorus-containing metabolites and substrates or muscle activation between Leg1ACT and Leg1PL and between Leg2ACT-CONTRA and Leg2PL-CONTRA (all P > 0.05). These findings suggest that levels of metabolic perturbation and muscle activation at Tlim are not different during single-leg severe-intensity knee-extensor exercise completed with or without prior fatiguing exercise of the contralateral leg. Despite contralateral fatigue, ACT ingestion did not alter neuromuscular responses, muscle metabolites, or exercise performance.

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. K E Y W O R D S cerebral blood flow, endothelial function, hypercapnic stimulus, reproducibility, transcranial Doppler ultrasound, youth 1 | INTRODUCTION Cerebrovascular reactivity (CVR) refers to the ability of the human brain to modulate cerebral blood flow in response to changes in stimuli, such as the partial pressure of arterial carbon dioxide (PaCO 2). Impairments in CVR are an important hallmark for cerebrovascular disease (CVD) progression. Research highlights that impairments in CVR in adults is associated with Alzheimer's disease, 1 neurocognitive decline, 2 stroke, 3,4 and independently predicts future CVD events in patients with CVD risk factors. 5 Impairments in CVR are present in

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 three experimental and one 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]. FMD increased 1 hour 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 hour following all conditions (P>0.57, 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 post MMTT (P=0.87, ES=0.02). Blood [uric acid] 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. Highlights: • 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.