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.

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.

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.

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.

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.

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.

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.

Submaximal exercise cardiac output is increased by 4 weeks of sprint interval training in young healthy males with low initial Q̇-V̇O2: Importance of cardiac response phenotype.

Cardiovascular adaptations to exercise, particularly at the individual level, remain poorly understood. Previous group level research suggests the relationship between cardiac output and oxygen consumption ([Formula: see text]-[Formula: see text]) is unaffected by training as submaximal [Formula: see text] is unchanged. We recently identified substantial inter-individual variation in the exercise [Formula: see text]-[Formula: see text] relationship that was correlated to stroke volume (SV) as opposed to arterial oxygen content. Therefore we explored the effects of sprint interval training (SIT) on modulating [Formula: see text]-[Formula: see text] given an individual's specific [Formula: see text]-[Formula: see text] relationship. 22 (21±2 yrs) healthy, recreationally active males participated in a 4-week SIT (8, 20 second sprints; 4x/week, 170% of the work rate at [Formula: see text] peak) study with progressive exercise tests (PET) until exhaustion. Cardiac output ([Formula: see text] L/min; inert gas rebreathe, Finometer Modelflow™), oxygen consumption ([Formula: see text] L/min; breath-by-breath pulmonary gas exchange), quadriceps oxygenation (near infrared spectroscopy) and exercise tolerance (6-20; Borg Scale RPE) were measured throughout PET both before and after training. Data are mean Δ from bsl±SD. Higher [Formula: see text] ([Formula: see text]) and lower [Formula: see text] ([Formula: see text]) responders were identified post hoc (n = 8/group). SIT increased the [Formula: see text]-[Formula: see text] post-training in [Formula: see text] (3.8±0.2 vs. 4.7±0.2; P = 0.02) while [Formula: see text] was unaffected (5.8±0.1 vs. 5.3±0.6; P = 0.5). [Formula: see text] was elevated beyond 80 watts in [Formula: see text] due to a greater increase in SV (all P<0.04). Peak [Formula: see text] (ml/kg/min) was increased in [Formula: see text] (39.7±6.7 vs. 44.5±7.3; P = 0.015) and [Formula: see text] (47.2±4.4 vs. 52.4±6.0; P = 0.009) following SIT, with [Formula: see text] having a greater peak [Formula: see text] both pre (P = 0.02) and post (P = 0.03) training. Quadriceps muscle oxygenation and RPE were not different between groups (all P>0.1). In contrast to [Formula: see text], [Formula: see text] responders are capable of improving submaximal [Formula: see text]-[Formula: see text] in response to SIT via increased SV. However, the increased submaximal exercise [Formula: see text] does not benefit exercising muscle oxygenation.

High-intensity interval exercise impairs neuroelectric indices of reinforcement-learning.

A single bout of high-intensity interval exercise (HIIE) improves behavioural measures of cognitive function; however, investigations using event-related potentials (ERPs) to examine the systems that underlie these cognitive improvements are lacking. The reward positivity is a positive-going ERP component that indexes reward processing evoked by 'win' feedback and is a candidate marker of an underlying human reinforcement learning system. While HIIE improves behavioural measures of learning, it is unknown how HIIE affects the amplitude of the reward positivity. Therefore, the purpose of this study was to investigate how HIIE affects reward positivity amplitude in response to reward feedback in university students. Using a single-group randomly assigned counterbalance crossover design, 25 healthy university students performed HIIE and control visits on separate days. Electroencephalographic data was recorded before (pre-intervention) and 10 min after (post-intervention) the intervention period while participants played a novel gambling task. The HIIE intervention consisted of 4 separate body-weight exercises totaling 11 min in duration, including rest. The control visit intervention consisted of quietly watching a nature documentary for 11 min. Heart rate (HR) was measured at the same time intervals in both trials. Analysis revealed that HIIE significantly diminished the amplitude of the reward positivity whereas it remained unaffected in the control condition. HR was significantly higher following HIIE compared to control during post-intervention testing. These findings suggest that mechanisms of reinforcement learning are impaired shortly after HIIE cessation, possibly due to persistent, suboptimal arousal as evidenced by elevated HR post-HIIE.

Exercise and circulating BDNF: Mechanisms of release and implications for the design of exercise interventions.

Engagement in regular bouts of exercise confers numerous positive effects on brain health across the lifespan. Acute bouts of exercise transiently improve cognitive function, while long-term exercise training stimulates brain plasticity, improves brain function, and helps to stave off neurological disease. The action of brain-derived neurotrophic factor (BDNF) is a candidate mechanism underlying these exercise-induced benefits and is the subject of considerable attention in the exercise-brain health literature. It is well established that acute exercise increases circulating levels of BDNF and numerous studies have sought to characterize this response for the purpose of improving brain health. Despite the interest in BDNF responses to exercise, little focus has been given to understanding the sources and mechanisms that underlie this response for the purpose of deliberately increasing circulating levels of BDNF. Here we review evidence to support that exploiting these mechanisms of BDNF release can help to optimize brain plasticity outcomes via exercise interventions, which could be especially relevant in the context of multimodal training (i.e., exercise and cognitive stimulation). Therefore, the purpose of this paper is to review the candidate sources of BDNF during exercise and the mechanisms of release. As well, we discuss strategies for maximizing BDNF responses to exercise, and propose novel research directions for advancing our understanding of these mechanisms.

Contribution of central and peripheral adaptations to changes in maximal oxygen uptake following 4 weeks of sprint interval training.

The current study examined the contribution of central and peripheral adaptations to changes in maximal oxygen uptake (V̇O2max) following sprint interval training (SIT). Twenty-three males completed 4 weekly SIT sessions (8 × 20-s cycling bouts at ∼170% of work rate at V̇O2max, 10-s recovery) for 4 weeks. Following completion of training, the relationship between changes in V̇O2max and changes in central (cardiac output) and peripheral (arterial-mixed venous oxygen difference (a-vO2diff), muscle capillary density, oxidative capacity, fibre-type distribution) adaptations was determined in all participants using correlation analysis. Participants were then divided into tertiles on the basis of the magnitude of their individual V̇O2max responses, and differences in central and peripheral adaptations were examined in the top (HI; ∼10 mL·kg-1·min-1 increase in V̇O2max, p < 0.05) and bottom (LO; no change in V̇O2max, p > 0.05) tertiles (n = 8 each). Training had no impact on maximal cardiac output, and no differences were observed between the LO group and the HI group (p > 0.05). The a-vO2diff increased in the HI group only (p < 0.05) and correlated significantly (r = 0.71, p < 0.01) with changes in V̇O2max across all participants. Muscle capillary density (p < 0.02) and ß-hydroxyacyl-CoA dehydrogenase maximal activity (p < 0.05) increased in both groups, with no between-group differences (p > 0.05). Citrate synthase maximal activity (p < 0.01) and type IIA fibre composition (p < 0.05) increased in the LO group only. Collectively, although the heterogeneity in the observed V̇O2max response following 4 weeks of SIT appears to be attributable to individual differences in systemic vascular and/or muscular adaptations, the markers examined in the current study were unable to explain the divergent V̇O2max responses in the LO and HI groups.

Exercise intolerance in Type 2 diabetes: is there a cardiovascular contribution?

Physical activity is critically important for Type 2 diabetes management, yet adherence levels are poor. This might be partly due to disproportionate exercise intolerance. Submaximal exercise tolerance is highly sensitive to muscle oxygenation; impairments in exercising muscle oxygen delivery may contribute to exercise intolerance in Type 2 diabetes since there is considerable evidence for the existence of both cardiac and peripheral vascular dysfunction. While uncompromised cardiac output during submaximal exercise is consistently observed in Type 2 diabetes, it remains to be determined whether an elevated cardiac sympathetic afferent reflex could sympathetically restrain exercising muscle blood flow. Furthermore, while deficits in endothelial function are common in Type 2 diabetes and are often cited as impairing exercising muscle oxygen delivery, no direct evidence in exercise exists, and there are several other vasoregulatory mechanisms whose dysfunction could contribute. Finally, while there are findings of impaired oxygen delivery, conflicting evidence also exists. A definitive conclusion that Type 2 diabetes compromises exercising muscle oxygen delivery remains premature. We review these potentially dysfunctional mechanisms in terms of how they could impair oxygen delivery in exercise, evaluate the current literature on whether an oxygen delivery deficit is actually manifest, and correspondingly identify key directions for future research.

Do interindividual differences in cardiac output during submaximal exercise explain differences in exercising muscle oxygenation and ratings of perceived exertion?

Considerable interindividual differences in the Q˙-V˙O2 relationship during exercise have been documented but implications for submaximal exercise tolerance have not been considered. We tested the hypothesis that these interindividual differences were associated with differences in exercising muscle deoxygenation and ratings of perceived exertion (RPE) across a range of submaximal exercise intensities. A total of 31 (21 ± 3 years) healthy recreationally active males performed an incremental exercise test to exhaustion 24 h following a resting muscle biopsy. Cardiac output (Q˙ L/min; inert gas rebreathe), oxygen uptake (V˙O2 L/min; breath-by-breath pulmonary gas exchange), quadriceps saturation (near infrared spectroscopy) and exercise tolerance (6-20; Borg Scale RPE) were measured. The Q˙-V˙O2 relationship from 40 to 160 W was used to partition individuals post hoc into higher (n = 10; 6.3 ± 0.4) versus lower (n = 10; 3.7 ± 0.4, P < 0.001) responders. The Q˙-V˙O2 difference between responder types was not explained by arterial oxygen content differences (P = 0.5) or peripheral skeletal muscle characteristics (P from 0.1 to 0.8) but was strongly associated with stroke volume (P < 0.05). Despite considerable Q˙-V˙O2 difference between groups, no difference in quadriceps deoxygenation was observed during exercise (all P > 0.4). Lower cardiac responders had greater leg (P = 0.027) and whole body (P = 0.03) RPE only at 185 W, but this represented a higher %peak V˙O2 in lower cardiac responders (87 ± 15% vs. 66 ± 12%, P = 0.005). Substantially lower Q˙-V˙O2 in the lower responder group did not result in altered RPE or exercising muscle deoxygenation. This suggests substantial recruitment of blood flow redistribution in the lower responder group as part of protecting matching of exercising muscle oxygen delivery to demand.

Absence of compensatory vasodilation with perfusion pressure challenge in exercise: evidence for and implications of the noncompensator phenotype.

Compromising oxygen delivery (O2D) during exercise requires compensatory vasodilatory and/or pressor responses to protect O2D:demand matching. The purpose of the study was to determine whether compensatory vasodilation is absent in some healthy young individuals in the face of a sudden reduction in exercising forearm perfusion pressure and whether this affects the exercise pressor response. Twenty-one healthy young men (21.6 ± 2.0 yr) completed rhythmic forearm exercise at a work rate equivalent to 70% of their own maximal exercise vasodilation. During steady-state exercise, the exercising arm was rapidly adjusted from below to above heart level, resulting in a reduction in forearm perfusion pressure of -30.7 ± 0.9 mmHg. Forearm blood flow (ml/min; brachial artery Doppler and echo ultrasound), mean arterial blood pressure (mmHg; finger photoplethysmography), and exercising forearm venous effluent (antecubital vein catheter) measurements revealed distinct compensatory vasodilatory differences. Thirteen individuals responded with compensatory vasodilation (509 ± 128 vs. 632 ± 136 ml·min-1·100 mmHg-1; P < 0.001), while eight individuals did not (663 ± 165 vs. 667 ± 167 ml·min-1·100 mmHg-1; P = 0.6). Compensatory pressor responses between groups were not different (5.5 ± 5.5 and 9.7 ± 9.5 mmHg; P = 0.2). Forearm blood flow, O2D, and oxygen consumption were all protected in compensators (all P > 0.05) but not in noncompensators, who therefore suffered compromises to exercise performance (6 ± 14 vs. -36 ± 29 N; P = 0.004). Phenotypic differences were not explained by potassium or nitric oxide bioavailability. In conclusion, both compensator and noncompensator vasodilator phenotype responses to a sudden compromise to exercising muscle blood flow are evident. Interindividual differences in the mechanisms governing O2D:demand matching should be considered as factors influencing exercise tolerance. NEW & NOTEWORTHY In healthy young individuals, compromising submaximally exercising muscle perfusion appears to evoke compensatory vasodilation to defend oxygen delivery. Here we report the absence of compensatory vasodilation in 8 of 21 such individuals, despite their vasodilatory capacity and increases in perfusion with increasing exercise intensity being indistinguishable from compensators. The absence of compensation impaired exercise tolerance. These findings suggest that interindividual differences in oxygen delivery:demand matching efficacy affect exercise tolerance and depend on the nature of a delivery:demand matching challenge.