The 'normal' adjustment of oxygen delivery to small muscle mass exercise is not optimized for muscle contractile function.

Oxygen delivery is viewed as tightly coupled to demand in exercise below critical power because increasing oxygen delivery does not increase V O 2 ${V_{{O_2}}}$ . However, whether the 'normal' adjustment of oxygen delivery to small muscle mass exercise in the heavy intensity domain is optimal for excitation-contraction coupling is currently unknown. In 20 participants (10 female), a remote skeletal muscle (i.e. tibialis anterior) metaboreflex was (Hyperperfusion condition) or was not (Control condition) activated for 4 min during both force of contraction (experimental model 1) and muscle activation-targeted (experimental model 2) rhythmic forearm handgrip exercise. Analysis was completed on the combined data from both experimental models. After 30 s of remote skeletal muscle metaboreflex activation, mean arterial blood pressure, forearm blood flow and muscle oxygenation were increased and remained increased until metaboreflex discontinuation. While oxygen delivery was elevated, the muscle activation to force of contraction ratio was improved. Upon metaboreflex discontinuation, forearm oxygen delivery and the muscle activation and force of contraction ratio rapidly (within 30 s) returned to control levels. These findings demonstrate that (a) the metaboreflex was effective at increasing forearm muscle oxygen delivery and oxygenation, (b) the muscle activation to force of contraction ratio was improved with increased oxygen delivery, and (c) in the heavy exercise intensity domain, the normal matching of oxygen delivery to metabolic demand is not optimal for muscle excitation-contraction coupling. These results suggest that the nature of vasoregulation in exercising muscle is such that it does not support optimal perfusion for excitation-contraction coupling. KEY POINTS: Oxygen delivery is viewed as tightly coupled to demand in exercise below critical power because increasing oxygen delivery does not increase the rate of oxygen uptake. Whether the 'normal' adjustment of oxygen delivery in small muscle mass exercise below critical power is optimal for excitation-contraction coupling is not known. Here we show in humans that increasing oxygen delivery above 'normal' improves excitation-contraction coupling. These results suggest that, in the heavy exercise intensity domain, the 'normal' matching of oxygen delivery to metabolic demand is not optimal for muscle excitation-contraction coupling. Therefore, the nature of vasoregulation in exercising muscle is such that it does not support optimal perfusion for excitation-contraction coupling.

Muscle contraction force conforms to muscle oxygenation during constant-activation voluntary forearm exercise.

NEW FINDINGS: What is the central question of this study? In electrically stimulated skeletal muscle, force production is downregulated when oxygen delivery is compromised and rapidly restored upon oxygen delivery restoration. Whether 'oxygen conforming' of force production occurs during voluntary muscle activation in humans and whether it is exercise intensity dependent remains unknown. What is the main finding and its importance? Here, we show in humans that force at a given voluntary muscle activation does conform to a decrease in oxygen delivery and recovers rapidly and completely with restoration of oxygen delivery. This oxygen-conforming response of contraction force appears to happen only at higher intensities. ABSTRACT: In electrically stimulated skeletal muscle, force production is downregulated when oxygen delivery is compromised and rapidly restored upon restoration of oxygen delivery in the absence of cellular disturbance. Whether this 'oxygen-conforming' response of force occurs and is exercise intensity dependent during stable voluntary muscle activation in humans is unknown. In 12 participants (six female), handgrip force, forearm muscle activation (EMG), muscle oxygenation and forearm blood flow (FBF) were measured during rhythmic handgrip exercise at forearm EMG achieving 50, 75 or 90% critical impulse (CI). Four minutes of brachial artery compression to reduce FBF by ∼60% (Hypoperfusion) or sham compression (adjacent to artery; Control) was performed during exercise. Sham compression had no effect. Hypoperfusion rapidly reduced muscle oxygenation at all exercise intensities, resulting in contraction force per muscle activation (force/EMG) progressively declining over 4 min by ∼16% at both 75 and 90% CI. No force/EMG decline occurred at 50% CI. Rapid restoration of muscle oxygenation after compression was closely followed by force/EMG such that it was not different from Control within 30 s for 90% CI and after 90 s for 75% CI. Our findings reveal that an oxygen-conforming response does occur in voluntary exercising muscle in humans. Within the exercise modality and magnitude of fluctuation of oxygenation in this study, the oxygen-conforming response appears to be exercise intensity dependent. Mechanisms responsible for this oxygen-conforming response have implications for exercise tolerance and warrant investigation.

Greater post-contraction hyperaemia below vs. above heart level: the role of active vasodilatation vs. passive mechanical distension of arterioles.

KEY POINTS: The immediate increase in skeletal muscle blood flow following contraction is greater when the contracting muscle is below vs. above heart level. This has been attributed to muscle pump-mediated venous emptying and subsequent widening of the arterial to venous pressure gradient, which can occur below but not above heart level. However, alternative explanations could include greater rapid onset vasodilatation and/or transmural pressure-mediated mechanical distension of resistance vessels, but these remain unexplored. We demonstrate that active vasodilatation is not responsible for greater post-contraction hyperaemia below the heart. Instead, an increased transmural pressure-mediated mechanical distension of resistance vessels is a key mechanism responsible for this phenomenon. Our findings establish the importance of considering/accounting for local mechanical arteriolar distension effects when investigating exercise hyperaemia. They also inform the application of exercise for rehabilitative purposes and prompt investigation into whether arteriolar distension accompanying vasodilatation is reduced with diseases or ageing, thereby compromising exercising muscle perfusion. ABSTRACT: We tested the hypotheses that increased post-contraction hyperaemia in higher (H; below heart) vs. lower (L; above heart) transmural pressure conditions is due to (1) greater active vasodilatation or (2) greater transmural pressure-mediated arteriolar distension. Participants (n = 20, 12 male, 8 female; combined mean age 24.5 ± 2 years) performed a 2 s isometric handgrip contraction, where arm position was maintained within or changed between H and L during contraction, resulting in four starting-finishing arm position conditions (LL, HL, LH, HH). Post-contraction forearm blood flow (echo and Doppler ultrasound) was higher with contraction release in H vs. L environments (P < 0.05). However, contraction initiated in H did not result in greater vasodilatation (forearm vascular conductance; FVC) than contraction initiated in L, regardless of contraction release condition (peak FVC: LL 217 ± 104 vs. HL 204 ± 92 ml min-1 (100 mmHg)-1 , P = 0.313, LH 229 ± 8 vs. HH 225 ± 85 ml min-1 (100 mmHg)-1 , P = 0.391; first post-contraction cardiac cycle FVC: same comparisons, both P = 0.317). However, FVC of the first post-contraction cardiac cycle was greater for contractions released in H vs. L regardless of pre-contraction condition (LL 106 ± 67 vs. LH 152 ± 76 ml min-1 (100 mmHg)-1 , P < 0.05; HL 80 ± 51 vs. HH 119 ± 58 ml min-1 (100 mmHg)-1 , P < 0.05). These findings refute the hypothesis that greater hyperaemia following a single contraction in higher transmural pressure conditions is due to greater active vasodilatation. Instead, our findings reveal a key role for increased transmural pressure-mediated mechanical distension of arterioles in creating a greater increase in vascular conductance for a given active vasodilatation following skeletal muscle contraction.

Assessment of resistance vessel function in human skeletal muscle: guidelines for experimental design, Doppler ultrasound, and pharmacology.

The introduction of duplex Doppler ultrasound almost half a century ago signified a revolutionary advance in the ability to assess limb blood flow in humans. It is now widely used to assess blood flow under a variety of experimental conditions to study skeletal muscle resistance vessel function. Despite its pervasive adoption, there is substantial variability between studies in relation to experimental protocols, procedures for data analysis, and interpretation of findings. This guideline results from a collegial discussion among physiologists and pharmacologists, with the goal of providing general as well as specific recommendations regarding the conduct of human studies involving Doppler ultrasound-based measures of resistance vessel function in skeletal muscle. Indeed, the focus is on methods used to assess resistance vessel function and not upstream conduit artery function (i.e., macrovasculature), which has been expertly reviewed elsewhere. In particular, we address topics related to experimental design, data collection, and signal processing as well as review common procedures used to assess resistance vessel function, including postocclusive reactive hyperemia, passive limb movement, acute single limb exercise, and pharmacological interventions.

Dietary nitrate supplementation and exercise tolerance in patients with heart failure with reduced ejection fraction.

Endothelial dysfunction and reduced nitric oxide (NO) signaling are key abnormalities leading to skeletal muscle oxygen delivery-utilization mismatch and poor physical capacity in patients with heart failure with reduced ejection fraction (HFrEF). Oral inorganic nitrate supplementation provides an exogenous source of NO that may enhance locomotor muscle function and oxygenation with consequent improvement in exercise tolerance in HFrEF. Thirteen patients (left ventricular ejection fraction ≤40%) were enrolled in a double-blind, randomized crossover study to receive concentrated nitrate-rich (nitrate) or nitrate-depleted (placebo) beetroot juice for 9 days. Low- and high-intensity constant-load cardiopulmonary exercise tests were performed with noninvasive measurements of central hemodynamics (stroke volume, heart rate, and cardiac output via impedance cardiography), arterial blood pressure, pulmonary oxygen uptake, quadriceps muscle oxygenation (near-infrared spectroscopy), and blood lactate concentration. Ten patients completed the study with no adverse clinical effects. Nitrate-rich supplementation resulted in significantly higher plasma nitrite concentration compared with placebo (240 ± 48 vs. 56 ± 8 nM, respectively; P < 0.05). There was no significant difference in the primary outcome of time to exercise intolerance between nitrate and placebo (495 ± 53 vs. 489 ± 58 s, respectively; P > 0.05). Similarly, there were no significant differences in central hemodynamics, arterial blood pressure, pulmonary oxygen uptake kinetics, skeletal muscle oxygenation, or blood lactate concentration from rest to low- or high-intensity exercise between conditions. Oral inorganic nitrate supplementation with concentrated beetroot juice did not present with beneficial effects on central or peripheral components of the oxygen transport pathway thereby failing to improve exercise tolerance in patients with moderate HFrEF.

Characteristics and effectiveness of vasodilatory and pressor compensation for reduced relaxation time during rhythmic forearm contractions.

NEW FINDINGS: What is the central question of this study? Reduced relaxation time between contractions in exercise requires increased vasodilatation and/or pressor response to prevent hypoperfusion and potential compromise to exercise tolerance. However, it remains unknown whether and to what extent local vasodilatation and/or systemic pressor compensation occurs and whether the efficacy of compensation is exercise intensity dependent. What is the main finding and its importance? We demonstrate that in a forearm exercise model vasodilatory but not pressor compensation occurs and is adequate to prevent hypoperfusion below but not above ∼40% peak work rate. Inadequate compensation occurs with exercise still well inside the submaximal domain, despite a vasodilatory reserve, and compromises exercise performance. During muscle contraction in rhythmic exercise, muscle blood flow is significantly impeded by microvascular compression. The purpose of this study was to establish the nature and magnitude of vasodilatory and/or pressor compensatory responses during forearm exercise in the face of an increased duration of mechanical microvascular compression, and whether the effectiveness of such compensation was exercise intensity dependent. Seven healthy males (21.0 ± 1.8 years old) completed progressive forearm exercise (24.5 N every 3 min; 2 s contraction-4 s relaxation duty cycle) in two conditions: control (CON), 2 s 100 mmHg forearm cuff inflation during contraction; and impedance (IMP), extension of cuff inflation 2 s beyond contraction. Forearm blood flow (in millilitres per minute); brachial artery Doppler and echo ultrasound), mean arterial blood pressure (in millimetres of mercury; finger photoplethysmography) and exercising forearm venous effluent (antecubital vein catheter) measurements revealed an exercise intensity-dependent compensatory vasodilatation effectiveness whereby increased vasodilatation fully protected forearm blood flow up to the 30% exercise intensity in IMP. Above this exercise intensity, forearm blood flow was defended only in part, although submaximal oxygen uptake was not compromised for any completed work rate. As a result, peak exercise intensity (175 ± 22 versus 196 ± 28 N, P = 0.04) and oxygen delivery (76 ± 14 versus 112 ± 22 ml O2  min-1 , P = 0.01) were significantly reduced in IMP compared with CON. In conclusion, reducing relaxation time compromised exercise capacity without compromise to oxygen uptake. Vasodilatory compensation was complete at lower but not higher exercise intensities, whereas pressor compensation was absent. The reasons for the exercise intensity dependence of the efficacy of vasodilatory compensation remain to be determined.

Reducing the volume of sprint interval training does not diminish maximal and submaximal performance gains in healthy men.

PURPOSE: The present study examined the effect of reducing sprint interval training (SIT) work-interval duration on increases in maximal and submaximal performance. METHODS: Subjects (n = 36) were assigned to one of three training groups: endurance training (ET; 60 min per session for weeks 1-2, increasing to 75 min per session for weeks 3-4), or sprint interval training consisting of either repeated 30 (SIT 30) or 15 (SIT 15) second all-out intervals (starting with 4 bouts per session for weeks 1-2, increasing to 6 intervals per session for weeks 3-4). Training consisted of cycling 3 times per week for 4 weeks. RESULTS: While there was a significant main effect of training on VO2peak such that VO2peak was elevated post-training, no significant difference was observed in the improvements observed between groups (ET ~13%, SIT 30-4%, SIT 15-8%). A significant main effect of training was observed such that lactate threshold and critical power were higher during post-testing across all groups (p < 0.05). There was a main effect of training (p < 0.05) on Wingate peak power with no differences observed between groups at post-training. CONCLUSIONS: Together, these results indicate that reducing SIT work-interval duration from 30 to 15 s had no impact on training-induced increases in aerobic or anaerobic power, or on increases in lactate threshold (absolute) and critical power.

Influence of acute dietary nitrate supplementation on oxygen delivery/consumption and critical impulse during maximal effort forearm exercise in males: a randomized crossover trial.

Beetroot juice supplementation (BRJ) increases nitric oxide bioavailability under conditions of hypoxia and acidosis, characteristics of maximal effort exercise, which is required to identify forearm critical impulse. We hypothesized BRJ would improve oxygen delivery:demand matching and forearm critical impulse performance. Healthy males (20.8±2.4 years) participated in a randomized crossover trial between October 2017-May 2018 (Queen's University, Kingston, ON). Participants completed 10-minutes of rhythmic maximal effort forearm handgrip exercise 2.5 hours post placebo (PL) vs. BRJ (9 completed PL/BRJ vs. 4 completed BRJ/PL) within a 2 week period. Data are presented as mean±SD. There was a main effect of drink (PL > BRJ) for oxygen extraction (P=0.033,ηp2=0.351) and oxygen consumption/force (P=0.017,ηp2=0.417). There was a drink x time interaction (PL > BRJ) for oxygen consumption/force (P=0.035,ηp2=0.216) between 75-360s (1.25-6 min) from exercise onset. BRJ did not influence oxygen delivery (P=0.953,ηp2=0.000), oxygen consumption (P=0.064,ηp2=0.278), metabolites [[lactate] (P=0.196,ηp2=0.135), pH (P=0.759,ηp2=0.008)] or power-duration performance parameters [critical impulse (P=0.379,d=0.253), W' (P=0.733,d=0.097)]. BRJ during all-out handgrip exercise does not influence oxygen delivery or exercise performance. Oxygen cost of contraction with BRJ is reduced as contraction impulse is declining during maximal effort exercise resulting in less oxygen extraction. https://osf.io/pga37/registrations.

Influence of acute dietary nitrate supplementation on oxygen delivery/consumption and limit of tolerance during progressive forearm exercise in men: a randomized crossover trial.

Beetroot juice (BRJ) supplementation increases nitric oxide bioavailability with hypoxia and acidosis, characteristics of high-intensity exercise. We investigated whether BRJ improved forearm oxygen delivery:demand matching in an intensity-dependent manner. Healthy men (21 ± 2.5 years) participated in a randomized crossover trial between October 2017 and May 2018 (Queen's University, Kingston, ON, Canada). Participants completed a forearm incremental exercise test to limit of tolerance (IET-LOT) 2.5 h post placebo (PL) versus BRJ (2 completed PL/BRJ vs. 9 completed BRJ/PL) within a 2-week period. Data are presented as mean ± standard deviation. There was a significant main effect of drink (PL < BRJ; P = 0.042, ηp2 = 0.385) and drink × intensity interaction for arteriovenous oxygen difference (PL < BRJ; P = 0.03; ηp2= 0.197; 20%-50% and 90% LOT). BRJ did not influence oxygen delivery (P = 0.893, ηp2 = 0.002), forearm blood flow (P = 0.589, ηp2 = 0.03) (forearm vascular conductance (P = 0.262, ηp2 = 0.124), mean arterial pressure (P = 0.254,ηp2 = 0.128)), oxygen consumption (P = 0.194, ηp2 = 0.179) or LOT (P = 0.432, d = 0.247). In healthy men, BRJ did not improve forearm oxygen delivery (vasodilatory or pressor response) during IET-LOT. Increased arteriovenous oxygen difference at submaximal intensities did not significantly influence oxygen consumption or performance across the entire range of forearm exercise intensities. This study adds to the growing body of evidence that BRJ does not influence small muscle mass blood flow in humans regardless of exercise intensity.

Does a single bout maximal effort forearm exercise test for determining critical impulse result in maximal oxygen delivery and consumption in men? A randomized crossover trial.

In a single bout maximal effort isometric forearm handgrip exercise test (maximal effort exercise test, MXT), contraction impulse exhibits exponential decay to an asymptote equivalent to critical impulse (CI). It is unknown whether oxygen delivery (O2del) and consumption (V˙O2) achieved at CI are maximal. Healthy men participated in a randomized crossover trial at Queen's University (Kingston, ON) between October 2017-May 2018. Participants completed an MXT and forearm incremental exercise test to limit of tolerance (IET-LOT) (7 completed MXT followed by IET-LOT vs. 4 completed IET-LOT followed by MXT) within a 2 week period. Data are presented as mean ± standard deviation. Maximal forearm blood flow (FBF) and O2del were not different in 11 men (21 ± 2.5 years) between MXT and IET-LOT (FBF = 473.8 ± 132.2 mL/min vs. 502.3 ± 152.3 mL/min; P = 0.482, ηp2 = 0.015; O2del = 85.2 ± 23.5 mL/min vs. 92.2 ± 37.0 mL/min; P = 0.456, ηp2 = 0.012). However, MXT resulted in greater maximal V˙O2 than IET-LOT (44.5 ± 15.2 mL/min > 36.8 ± 11.4 mL/min; P = 0.007, ηp2 = 0.09), due to greater oxygen extraction (54.0 ± 10.0% > 44.4 ± 8.6%; P = 0.021, ηp2 = 0.185). As CI was 88.6 ± 8.2% of IET-LOT contraction impulse, maximal O2 cost of contractions in MXT was greater than IET-LOT (0.45 ± 0.14 mL/min/Ns > 0.33 ± 0.09 mL/min/Ns; P < 0.001, ηp2 = 0.166). In healthy men, MXT identifying CI results in similar peak oxygen delivery but greater peak V˙O2 via increased extraction compared to an IET-LOT, indicating increased oxygen cost. MXT-CI may better estimate maximal V˙O2 than traditional IET-LOT for this exercise modality.

Lower limb-localized vascular phenomena explain initial orthostatic hypotension upon standing from squat.

The cause(s) of initial orthostatic hypotension (transient fall in blood pressure within 15 s upon active rising) have not been established. We tested the hypothesis that this hypotension is due to local vascular phenomena in contracting leg muscles from the brief effort of standing up. Seventeen young healthy subjects (2 male and 15 female, 22.5 ± 1.0 years) performed an active rise from resting squat after a 10-s squat, a 1-min squat, or a 5-min squat. Beat-by-beat arterial blood pressure, cardiac output, heart rate, and stroke volume (Finometer finger photoplethysmography) and right common femoral artery blood flow (Doppler and Echo ultrasound) were recorded. Data are means ± SE. Quiet standing before squat represented baseline. Peak increases in lower limb and total vascular conductance (ml·min(-1)·mmHg(-1)) upon standing were not different within squat conditions (10-s squat, 50.0 ± 12.4 vs. 44.3 ± 5.0; 1-min squat, 54.7 ± 9.2 vs. 50.5 ± 4.5; 5-min squat, 67.4 ± 13.7 vs. 58.8 ± 3.9; all P > 0.574). Mean arterial blood pressure (in mmHg) fell to a nadir well below standing baseline in all conditions despite increases in cardiac output. The hypotension predicted by the increase in leg vascular conductance accounted for this hypotension [observed vs. predicted (in mmHg): 10-s squat, -17.1 ± 2.1 vs. -18.3 ± 5.5; 1-min squat, -22.0 ± 3.8 vs. -25.3 ± 4.9; 5-min squat, -28.3 ± 4.0 vs. -29.2 ± 6.7]. We conclude that rapid contraction induced dilation in leg muscles with the effort of standing, along with a minor potential contribution of elevated lower limb arterio-venous pressure gradient, outstrips compensatory cardiac output responses and is the cause of initial orthostatic hypotension upon standing from squat.

Heterogenous vasodilator pathways underlie flow-mediated dilation in men and women.

This study investigated the sex differences in the contribution of nitric oxide (NO) and prostaglandins (PGs) to flow-mediated dilation (FMD). Radial artery (RA) FMD, assessed as the dilatory response to 5-min distal cuff occlusion, was repeated after three separate brachial artery infusions of saline (SAL), N(G)-monomethyl-L-arginine (L-NMMA), and ketorolac (KETO) + L-NMMA in healthy younger men (M; n = 8) and women (W; n = 8). In eight subjects (4 M, 4W) RA FMD was reassessed on a separate day with drug order reversed (SAL, KETO, and L-NMMA + KETO). RA FMD was calculated as the peak dilatory response observed relative to baseline (%FMD) and expressed relative to the corresponding area under the curve shear stress (%FMD/AUC SS). L-NMMA reduced %FMD similarly and modestly (P = 0.68 for sex * trial interaction) in M and W (all subjects: 10.0 ± 3.8 to 7.6 ± 4.7%; P = 0.03) with no further effect of KETO (P = 0.68). However, all sex * trial and trial effects on %FMD/AUC SS for l-NMMA and KETO + l-NMMA were insignificant (all P > 0.20). There was also substantial heterogeneity of the magnitude and direction of dilator responses to blockade. After l-NMMA infusion, subjects exhibited both reduced (n = 14; range: 11 to 78% decrease) and augmented (n = 2; range: 1 to 96% increase) %FMD. Following KETO + l-NMMA, seven subjects exhibited reduced dilation (range: 10 to 115% decrease) and nine subjects exhibited augmented dilation (range: 1 to 212% increase). Reversing drug order did not change the nature of the findings. These findings suggest that RA FMD is not fully or uniformly NO dependent in either men or women, and that there is heterogeneity in the pathways underlying the conduit dilatory response to ischemia.

Assessment of flow-mediated dilation in humans: a methodological and physiological guideline.

Endothelial dysfunction is now considered an important early event in the development of atherosclerosis, which precedes gross morphological signs and clinical symptoms. The assessment of flow-mediated dilation (FMD) was introduced almost 20 years ago as a noninvasive approach to examine vasodilator function in vivo. FMD is widely believed to reflect endothelium-dependent and largely nitric oxide-mediated arterial function and has been used as a surrogate marker of vascular health. This noninvasive technique has been used to compare groups of subjects and to evaluate the impact of interventions within individuals. Despite its widespread adoption, there is considerable variability between studies with respect to the protocols applied, methods of analysis, and interpretation of results. Moreover, differences in methodological approaches have important impacts on the response magnitude, can result in spurious data interpretation, and limit the comparability of outcomes between studies. This review results from a collegial discussion between physiologists with the purpose of developing considered guidelines. The contributors represent several distinct research groups that have independently worked to advance the evidence base for improvement of the technical approaches to FMD measurement and analysis. The outcome is a series of recommendations on the basis of review and critical appraisal of recent physiological studies, pertaining to the most appropriate methods to assess FMD in humans.

Brachial artery flow-mediated dilation is not affected by pregnancy or regular exercise participation.

Whether brachial artery FMD (flow-mediated dilation) is altered in pregnancy by 28-35 weeks compared with non-pregnant women remains controversial. The controversy may be due to limitations of previous studies that include failing to: (i) test non-pregnant controls in the mid-late luteal phase, (ii) account for effects of pregnancy on the dilatory shear stimulus, (iii) account for physical activity or (iv) control for inter-individual variation in the time to peak FMD. In the present study, brachial artery FMD was measured in 17 active and eight sedentary pregnant women (34.1±1.6 weeks of gestation), and in 19 active and 11 sedentary non-pregnant women (mid-late luteal phase). Decreased vascular tone secondary to increased shear stress contributes minimally to pregnancy-induced increases in baseline brachial artery diameter, as shear stress removal during distal cuff inflation in pregnant women did not reduce diameter to baseline levels observed in non-pregnant controls. Neither the shear stimulus nor the percentage FMD was affected by pregnancy or regular exercise. Continuous diameter measurements are required to control for delayed peak dilation during pregnancy (57±15 compared with 46±15 s; P=0.012), as post-release diameter measured at 60 or 55-65 s post-release underestimated FMD to a greater extent in non-pregnant than in pregnant women.

Perceived mental strain dissociates from perceived physical strain during relative intensity submaximal exercise on ascent from low to high altitude.

Perceived fatigability, which has perception of physical strain and of mental strain as its components, can impact exercise tolerance. Upon ascent to high altitude, low landers experience reduced exercise capacity and reduced tolerance for a given absolute submaximal work rate. It is established that perceived physical strain tracks with relative exercise intensity. However, it is not known how altitude ascent affects perceived mental strain relative to perceived physical strain. We tested the hypothesis that when exercising at the same relative exercise intensity perceived physical strain will remain unchanged whereas perceived mental strain will decrease on ascent from low to high altitude in the Everest region in Nepal. Twelve hours after arriving at each of three elevations; 1400 m, 3440 m, and 4240 m, 12 untrained participants used the task effort awareness (TEA) and physical-rating of perceived exertion (P-RPE) scales to report perceived mental and physical strain during a 20 min walking test at a self-monitored heart rate reserve (HRR) range of 40-60% (Polar HR Monitor). TEA and P-RPE were recorded twice during exercise (5-7 min and 14-16 min). Neither P-RPE (1400 m: 11.1 ± 1.8, 3440 m: 10.7 ± 1.2, 4240 m: 11.5 ± 1.5) nor %HRR (1400 m: 55.25 ± 7.34, 3440 m: 51.70 ± 6.70, 4240 m: 50.17 ± 4.02) changed as altitude increased. TEA decreased at 4240 m (2.05 ± 0.71) compared to 1400 m (3.44 ± 0.84)--this change was not correlated with any change in %HRR nor was it due to a change in core affect. These findings support our hypothesis and demonstrate the independence of perceived physical and perceived mental strain components of perceived fatigability. Implications for exercise tolerance remain to be determined.

A novel gravity-induced blood flow restriction model augments ACC phosphorylation and PGC-1α mRNA in human skeletal muscle following aerobic exercise: a randomized crossover study.

This study tested the hypothesis that a novel, gravity-induced blood flow restricted (BFR) aerobic exercise (AE) model will result in greater activation of the AMPK-PGC-1α pathway compared with work rate-matched non-BFR. Thirteen healthy males (age: 22.4 ± 3.0 years; peak oxygen uptake: 42.4 ± 7.3 mL/(kg·min)) completed two 30-min work rate-matched bouts of cycling performed with their legs below (CTL) and above their heart (BFR) at ∼2 weeks apart. Muscle biopsies were taken before, immediately, and 3 h after exercise. Blood was drawn before and immediately after exercise. Our novel gravity-induced BFR model led to less muscle oxygenation during BFR compared with CTL (O2Hb: p = 0.01; HHb: p < 0.01) and no difference in muscle activation (p = 0.53). Plasma epinephrine increased following both BFR and CTL (p < 0.01); however, only norepinephrine increased more following BFR (p < 0.01). PGC-1α messenger RNA (mRNA) increased more following BFR (∼6-fold) compared with CTL (∼4-fold; p = 0.036). VEGFA mRNA increased (p < 0.01) similarly following BFR and CTL (p = 0.21), and HIF-1α mRNA did not increase following either condition (p = 0.21). Phosphorylated acetyl-coenzyme A carboxylase (ACC) increased more following BFR (p < 0.035) whereas p-PKA substrates, p-p38 MAPK, and acetyl-p53 increased (p < 0.05) similarly following both conditions (p > 0.05). In conclusion, gravity-induced BFR is a viable BFR model that demonstrated an important role of AMPK signalling on augmenting PGC-1α mRNA. Novelty Gravity-induced BFR AE reduced muscle oxygenation without impacting muscle activation, advancing gravity-induced BFR as a simple, inexpensive BFR model. Gravity-induced BFR increased PGC-1α mRNA and ACC phosphorylation more than work rate-matched non-BFR AE. This is the first BFR AE study to concurrently measure blood catecholamines, muscle activation, and muscle oxygenation.

Acute aerobic exercise impairs aspects of cognitive function at high altitude.

Hypoxia-mediated cognitive dysfunction can be transiently mitigated by exercise in a laboratory-based setting. Whether this effect holds true in the context of high altitude hypoxia has not been determined. We investigated the effect of acute aerobic exercise on cognitive function (CF) at low (1400m) and high altitude (4240m). Fifteen volunteers (24.1±3.5yrs; 9 females) exercised for 20-min at 40-60% of their heart rate reserve at low and high altitude. CF was assessed before and 10-min after exercise using a tablet-based battery of executive function tests. A sea-level control group (n=13; 24.2±2.4 years; 9 females) performed time-matched CF tests to assess the contribution of a learning effects due to repeated testing. Measures of resting CF were unaffected by ascent to high altitude. Following high altitude exercise, performance significantly worsened on the digit symbol substitution task - a test of processing speed, working memory, and visuospatial attention (z=0.01 vs. -0.59, p=0.02, η2=0.35). No effect was found on other measures of CF following exercise. There was no association between changes in peripheral oxygen saturation and changes in CF following high altitude exercise (r=0.22, p=0.44), but higher hemoglobin concentration at high altitude was associated with a decline in CF following exercise at high altitude (r=-0.65, p=0.02). Acute aerobic exercise performed at high altitude impairs some aspects of CF, whereas other CF tests remain unchanged. The strong ecological validity of this study warrants attention and follow-up investigations are needed to better characterize selective impairment of CF with high altitude exercise.

A comparison of pain responses, hemodynamic reactivity and fibre type composition between Bergström and microbiopsy skeletal muscle biopsies.

This study tested the hypotheses that 1) skeletal muscle biopsies performed with the Bergström needle evoke larger perceptions of pain and greater hemodynamic reactivity compared to biopsies performed with the microbiopsy needle, and 2) both needles yield samples with similar fibre type compositions when samples are collected at similar skeletal muscle depths. Fourteen healthy (age: 21.6 ±â€¯3.2 years; VO2peak: 41.5 ±â€¯5.8 mL/kg/min) males (n = 7) and females (n = 7) provided two resting skeletal muscle biopsies, one with each needle type, following a randomized crossover design. Participants completed the short-form McGill Pain Questionnaire and the Brief Pain Inventory before, during, and after the skeletal muscle biopsies. Hemodynamic reactivity was assessed by measuring heart rate (HR) and mean arterial pressure (MAP) at rest and during the biopsy procedures. Immunofluorescence analysis was used to assess fibre type composition in vastus lateralis samples. Compared to the microbiopsy needle, the Bergström needle elicited a larger perception of pain but similar hemodynamic reactivity during the biopsy. Both needles yielded skeletal muscle samples with similar fibre type composition and resulted in similar perceptions of pain and pain-related interference during the post-biopsy recovery period. Collectively, these findings suggest that studies should consider using the microbiopsy needle rather than the Bergström needle unless large amounts of muscle tissue or certain muscle fibre lengths are required. However, future work should determine whether our findings are generalizable to biopsies performed with different procedures and/or types of Bergström/microbiopsy needles.