Non-exercised Muscle Research Articles

Microvascular Reactivity Is Greater Following Blood Flow Restriction Resistance Exercise Compared with Traditional Resistance Exercise.

Perlet, MR, Hosick, PA, Licameli, N, and Matthews, EL. Microvascular reactivity is greater following blood flow restriction resistance exercise compared with traditional resistance exercise. J Strength Cond Res XX(X): 000-000, 2024-Chronic blood flow restriction (BFR) resistance exercise can improve muscular strength, hypertrophy, and microvasculature function, but the acute microvascular effects are unknown. We aimed to test the effects of acute BFR resistance exercise on postexercise microvascular reactivity in an exercising muscle and nonexercising muscle compared with traditional resistance exercise (TRE). Twenty-five adults (men = 14, women = 11, age: 22 ± 3 years, body mass: 71.69 ± 14.49 kg, height: 170 ± 10 cm) completed barbell back squat 1-repetition maximum (1RM) testing followed by 2 randomized and counterbalanced resistance exercise visits separated by ≥48 hours. The 2 visits involved either BFR (4 sets of 30-15-15-15 repetitions at 30% 1RM, with 60-second rest intervals) or TRE (4 sets of 10 repetitions at 70% 1RM, 60-second rest intervals). During each exercise visit, a pre- and postbarbell back squat vascular occlusion test was performed using near-infrared spectroscopy to measure skeletal muscle oxygen (SmO2) in the vastus lateralis (VL) and flexor carpi radialis (FCR). Two-way repeated-measures ANOVA found an interaction effect (p = 0.020) for SmO2 reactivity in the VL. Post hoc analysis found greater reactive hyperemia postexercise in the VL for the BFR condition (p < 0.001) but not the TRE condition (p ≥ 0.05). There were no time, condition, or interaction effects (all p > 0.05) for the same analysis in the FCR. This analysis suggests that BFR, but not TRE, lead to acutely improved microvasculature function. Moreover, it suggests that the effects of BFR resistance exercise are local to the exercised or occluded limb and not systemic.

Skeletal muscle p53-depletion uncovers a mechanism of fuel usage suppression that enables efficient energy conservation.

The ability of skeletal muscle to respond adequately to changes in nutrient availability, known as metabolic flexibility, is essential for the maintenance of metabolic health and loss of flexibility contributes to the development of diabetes and obesity. The tumour suppressor protein, p53, has been linked to the control of energy metabolism. We assessed its role in the acute control of nutrient allocation in skeletal muscle in the context of limited nutrient availability. A mouse model with inducible deletion of the p53-encoding gene, Trp53, in skeletal muscle was generated using the Cre-loxP-system. A detailed analysis of nutrient metabolism in mice with control and knockout genotypes was performed under ad libitum fed and fasting conditions and in exercised mice. Acute deletion of p53 in myofibres of mice activated catabolic nutrient usage pathways even under ad libitum fed conditions, resulting in significantly increased overall energy expenditure (+10.6%; P=0.0385) and a severe nutrient deficit in muscle characterized by depleted intramuscular glucose and glycogen levels (-62,0%; P<0.0001 and -52.7%; P<0.0001, respectively). This was accompanied by changes in marker gene expression patterns of circadian rhythmicity and hyperactivity (+57.4%; P=0.0068). These metabolic changes occurred acutely, within 2-3days after deletion of Trp53 was initiated, suggesting a rapid adaptive response to loss of p53, which resulted in a transient increase in lactate release to the circulation (+46.6%; P=0.0115) from non-exercised muscle as a result of elevated carbohydrate mobilization. Conversely, an impairment of proteostasis and amino acid metabolism was observed in knockout mice during fasting. During endurance exercise testing, mice with acute, muscle-specific Trp53 inactivation displayed an early exhaustion phenotype with a premature shift in fuel usage and reductions in multiple performance parameters, including a significantly reduced running time and distance (-13.8%; P=0.049 and -22.2%; P=0.0384, respectively). These findings suggest that efficient nutrient conservation is a key element of normal metabolic homeostasis that is sustained by p53. The homeostatic state in metabolic tissues is actively maintained to coordinate efficient energy conservation and metabolic flexibility towards nutrient stress. The acute deletion of Trp53 unlocks mechanisms that suppress the activity of nutrient catabolic pathways, causing substantial loss of intramuscular energy stores, which contributes to a fasting-like state in muscle tissue. Altogether, these findings uncover a novel function of p53 in the short-term regulation of nutrient metabolism in skeletal muscle and show that p53 serves to maintain metabolic homeostasis and efficient energy conservation.

The Duration of Non-Local Muscle Fatigue Effects.

Non-local muscle fatigue (NLMF) refers to a transient decline in the functioning of a non-exercised muscle following the fatigue of a different muscle group. Most studies examining NLMF conducted post-tests immediately after the fatiguing protocols, leaving the duration of these effects uncertain. The aim of this study was to investigate the duration of NLMF (1-, 3-, and 5-minutes). In this randomized crossover study, 17 recreationally trained participants (four females) were tested for the acute effects of unilateral knee extensor (KE) muscle fatigue on the contralateral homologous muscle strength, and activation. Each of the four sessions included testing at either 1-, 3-, or 5-minutes post-test, as well as a control condition for non-dominant KE peak force, instantaneous strength (force produced within the first 100-ms), and vastus lateralis and biceps femoris electromyography (EMG). The dominant KE fatigue intervention protocol involved two sets of 100-seconds maximal voluntary isometric contractions (MVIC) separated by 1-minute of rest. Non-dominant KE MVIC forces showed moderate and small magnitude reductions at 1-min (p < 0.0001, d = 0.72) and 3-min (p = 0.005, d = 0.30) post-test respectively. The KE MVIC instantaneous strength revealed large magnitude, significant reductions between 1-min (p = 0.021, d = 1.33), and 3-min (p = 0.041, d = 1.13) compared with the control. In addition, EMG data revealed large magnitude increases with the 1-minute versus control condition (p = 0.03, d = 1.10). In summary, impairments of the non-exercised leg were apparent up to 3-minutes post-exercise with no significant deficits at 5-minutes. Recovery duration plays a crucial role in the manifestation of NLMF.

Mast cell degranulation is greater when exposed to dialysate collected from exercising skeletal muscle

The effect of histamine is multifaceted and potentially triggers a broad range of cellular adaptations contributing to vascular function, cellular maintenance, metabolism, and inflammation. During exercise, histamine is released from skeletal muscle. This response and the subsequent actions of histamine appear important in obtaining many of the beneficial adaptations to exercise. Increases in exercising skeletal muscle histamine release, in part, occur due to mast cell degranulation. However, the direct effect of exercise on mast cell degranulation has yet to be elucidated. To that end, this preliminary study aimed to quantify in vitro mast cell degranulation when cells are exposed to dialysate taken from exercising and non-exercising skeletal muscle. We hypothesized that greater mast cell degranulation would occur when exposed to dialysate collected from exercising skeletal muscle compared to dialysate collected from non-exercising muscle. Ten subjects (5M/5F, age 26 ± 5 years, weight 76 ± 17 kg, height 168 ± 12 cm) completed 60 minutes of single-leg dynamic knee extension exercise. Prior to exercise, a microdialysis probe was inserted into the vastus lateralis of the exercising and non-exercising legs and perfused with saline at a rate of 5 uL/min. Dialysate was collected before and every 20 minutes during exercise and the subsequent one-hour recovery period. In the exercising skeletal muscle, mast cell degranulation (quantified via b-hexosaminidase release) was greater when exposed to dialysate during exercise versus dialysate collected pre-exercise (P &lt; 0.05). Compared to non-exercising leg dialysate, degranulation was greater for exercising leg dialysate taken between minutes 20 and 40 into exercise (20.6 ± 2.7% vs 15.8 ± 2.0%, P &lt; 0.05) and 40 and 60 into exercise (24.0 ± 2.6 % vs 15.0 ± 2.7 %, P &lt; 0.001) and remained greater for dialysate taken in the first 20 minutes of recovery (21.4 ± 2.8% vs 15.2 ± 3.0%, P &lt; 0.05). These data suggest that there is a soluble factor released from exercising skeletal muscle that causes mast cell degranulation in vitro. These preliminary findings establish a bioassay for further exploration of the identity of the soluble factor released from exercising skeletal muscle, which is responsible for mast cell degranulation in vivo. This research was supported in part by National Institutes of Health Grants AG072805 and HL115027. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Immediate crossover fatigue after unilateral submaximal eccentric contractions of the knee flexors involves peripheral alterations and increased global perceived fatigue.

After a unilateral muscle exercise, the performance of the non-exercised contralateral limb muscle can be also impaired. This crossover fatigue phenomenon is still debated in the literature and very few studies have investigated the influence of eccentric contractions. This study was designed to assess neuromuscular adaptations involved in the crossover fatigue of the non-exercised contralateral knee flexor muscles. Seventeen healthy young men performed a unilateral submaximal eccentric exercise of the right knee flexors until a 20% reduction in maximal voluntary isometric contraction torque was attained in the exercised limb. Before (PRE), immediately after exercise cessation (POST) and 24 hours later (POST24), neuromuscular function and perceived muscle soreness were measured in both the exercised limb and non-exercised limb. In addition, global perceived fatigue was assessed at each measurement time. At POST, significant reductions in maximal voluntary isometric contraction were observed in the exercised limb (-28.1%, p < 0.001) and in the non-exercised limb (-8.5%, p < 0.05), evidencing crossover fatigue. At POST, voluntary activation decreased in the exercised limb only (-6.0%, p < 0.001), while electrically evoked potentiated doublet torque was impaired in both the exercised limb and the non-exercised limb (-11.6%, p = 0.001). In addition, global perceived fatigue significantly increased at POST (p < 0.001). At POST24, all measured variables returned to PRE values, except for perceived muscle soreness scores exhibiting greater values than PRE (p < 0.05). A possible cumulative interaction between peripheral alterations and global perceived fatigue may account for the immediate crossover fatigue observed in the non-exercised limb.

The acute effect of respiratory muscle training on microcirculation in patients with chronic heart failure

Background: Patients with chronic heart failure (CHF) present microcirculation alterations and vascular endothelial dysfunction. Exercise training programs have been shown to improve the functional status of these patients, however less is known yet about the acute systemic effect of exercise on peripheral muscle microcirculation. The aim of the present study was to investigate the acute effect of a respiratory muscle exercise bout on the microcirculation of non-exercising muscles (systemic effect). Materials and Methods: Thirty-four (30♂/4♀) stable CHF patients, with a mean age of61.4±9.2 years, ejection fraction (EF): 33.9±7.8%, maximal inspiratory pressure (MIP): 78.2±27.1 cmH2O, VO2max: 17.5±4.05 ml/kg/min, VE/VCO2 slope: 32.7±6.4 and a New York Heart Association classification (NYHA) ≥ ΙΙ participated in the study. Microcirculatory assessment was performed at rest and immediately after the respiratory exercise program (5 sets/10 repetitions, training load: 60% of MIP). Basal tissue oxygen saturation (StO2),oxygen consumption rate (OCR) and reperfusion rate (RR) were measured utilizing near-infrared spectroscopy(NIRS) at the thenar muscle along with the vascular occlusion test (VOT). Results: RR (%/min), following the release of vascular occlusion, as well as OCR (%/min) increased after the respiratory exercise program (from 3.4±1.6 to 3.9±1.7, p=0.007, and from 12.7±3.8 to 13.2±3.9, p=0.021 respectively), whereas the corresponding basal StO2values difference did not reach the level of statistical significance (from 85.5±6.4. to 84.7±6.2, p=0.065). Conclusions: In the present study, concerning patients with CHF, after an acute respiratory exercise bout, dynamic microcirculatory indices assessed by NIRS in peripheral, non-exercising muscles, were significantly altered.

Acute High-Intensity Interval Exercise Modulates Corticospinal Excitability in Older Adults.

Acute exercise can modulate the excitability of the nonexercised upper limb representation in the primary motor cortex (M1). Measures of M1 excitability using transcranial magnetic stimulation (TMS) are modulated after various forms of acute exercise in young adults, including high-intensity interval training (HIIT). However, the impact of HIIT on M1 excitability in older adults is currently unknown. Therefore, the purpose of the current study was to investigate the effects of lower limb cycling HIIT on bilateral upper limb M1 excitability in older adults. We assessed the impact of acute lower limb HIIT or rest on bilateral corticospinal excitability, intracortical inhibition and facilitation, and interhemispheric inhibition of the nonexercised upper limb muscle in healthy older adults (mean age 66 ± 8 yr). We used single and paired-pulse TMS to assess motor evoked potentials, short-interval intracortical inhibition, intracortical facilitation, and the ipsilateral silent period. Two groups of healthy older adults completed either HIIT exercise or seated rest for 23 min, with TMS measures performed before (T0), immediately after (T1), and 30 min after (T2) HIIT/rest. Motor evoked potentials were significantly increased after HIIT exercise at T2 compared with T0 in the dominant upper limb. Contrary to our hypothesis, we did not find any significant change in short-interval intracortical inhibition, intracortical facilitation, or ipsilateral silent period after HIIT. Our findings demonstrate that corticospinal excitability of the nonexercised upper limb is increased after HIIT in healthy older adults. Our results indicate that acute HIIT exercise impacts corticospinal excitability in older adults, without affecting intracortical or interhemispheric circuitry. These findings have implications for the development of exercise strategies to potentiate neuroplasticity in healthy older and clinical populations.

Genomic and Epigenomic Evaluation of Electrically Induced Exercise in People With Spinal Cord Injury: Application to Precision Rehabilitation.

Physical therapists develop patient-centered exercise prescriptions to help overcome the physical, emotional, psychosocial, and environmental stressors that undermine a person's health. Optimally prescribing muscle activity for people with disability, such as a spinal cord injury, is challenging because of their loss of volitional movement control and the deterioration of their underlying skeletal systems. This report summarizes spinal cord injury-specific factors that should be considered in patient-centered, precision prescription of muscle activity for people with spinal cord injury. This report also presents a muscle genomic and epigenomic analysis to examine the regulation of the proliferator-activated receptor γ coactivator 1α (PGC-1α) (oxidative) and myostatin (hypertrophy) signaling pathways in skeletal muscle during low-frequency (lower-force) electrically induced exercise versus higher-frequency (higher-force) electrically induced exercise under constant muscle recruitment (intensity). Seventeen people with spinal cord injury participated in 1 or more unilateral electrically induced exercise sessions using a lower-force (1-, 3-, or 5-Hz) or higher-force (20-Hz) protocol. Three hours after the exercise session, percutaneous muscle biopsies were performed on exercised and nonexercised muscles for genomic and epigenomic analysis. We found that low-frequency (low-force) electrically induced exercise significantly increased the expression of PGC-1α and decreased the expression of myostatin, consistent with the expression changes observed with high-frequency (higher-force) electrically induced exercise. Further, we found that low-frequency (lower-force) electrically induced exercise significantly demethylated, or epigenetically promoted, the PGC-1α signaling pathway. A global epigenetic analysis showed that >70 pathways were regulated with low-frequency (lower-force) electrically induced exercise. These novel results support the notion that low-frequency (low-force) electrically induced exercise may offer a more precise rehabilitation strategy for people with chronic paralysis and severe osteoporosis. Future clinical trials are warranted to explore whether low-frequency (lower-force) electrically induced exercise training affects the overall health of people with chronic spinal cord injury.

Acute Exercise Modulates the Excitability of Specific Interneurons in Human Motor Cortex

Acute exercise can modulate the excitability of the non-exercised upper-limb representation in the primary motor cortex (M1). Accumulating evidence demonstrates acute exercise affects measures of M1 intracortical excitability, with some studies also showing altered corticospinal excitability. However, the influence of distinct M1 interneuron populations on the modulation of intracortical and corticospinal excitability following acute exercise is currently unknown. We assessed the impact of an acute bout of leg cycling exercise on unique M1 interneuron excitability of a non-exercised intrinsic hand muscle using transcranial magnetic stimulation (TMS) in young adults. Specifically, posterior-to-anterior (PA) and anterior-to-posterior (AP) TMS current directions were used to measure the excitability of distinct populations of interneurons before and after an acute bout of exercise or rest. Motor evoked potentials (MEPs) and short-interval intracortical inhibition (SICI) were measured in the PA and AP current directions in M1 at two time points separated by 25 min of rest, as well as immediately and 30 min after a 25-minute bout of moderate-intensity cycling exercise. Thirty minutes after exercise, MEP amplitudes were significantly larger than other timepoints when measured with AP current, whereas MEP amplitudes derived from PA current did not show this effect. Similarly, SICI was significantly decreased immediately following acute exercise measured with AP but not PA current. Our findings suggest that the excitability of unique M1 interneurons are differentially modulated by acute exercise. These results indicate that M1 interneurons preferentially activated by AP current may play an important role in the exercise-induced modulation of intracortical and corticospinal excitability.

Pain and executive function: no association between remote exercise-induced hypoalgesia and cognitive inhibition in pain-free participants.

Cognitive inhibition, which denotes the ability to suppress predominant or automatic responses, has been associated with lower pain sensitivity and larger conditioned pain modulation in humans. Studies exploring the association between cognitive inhibition and other pain inhibitory phenomena, like exercise-induced hypoalgesia (EIH), are scarce. The primary aim was to explore the association between cognitive inhibition and EIH at exercising (local) and non-exercising (remote) muscles after isometric exercise. The secondary aim was to explore the association between cognitive inhibition and pressure pain sensitivity. Sixty-six pain-free participants (28.3±8.9 years old, 34 women) completed two cognitive inhibition tasks (stop-signal task and Stroop Colour-Word task), a 3-min isometric wall squat exercise, and a quiet rest control condition with pre- and post-assessments of manual pressure pain thresholds at a local (thigh) and a remote site (shoulder). In addition, cuff pressure pain thresholds, pain tolerance and temporal summation of pain were assessed at baseline. No association was found between remote EIH and cognitive inhibition (Stroop interference score: r=0.12, [-0.15; 0.37], p=0.405, BF01=6.70; stop-signal reaction time: r=-0.08, [-0.32; 0.17], p=0.524, BF01=8.32). Unexpectedly, individuals with worse performance on the Stroop task, as indicated by a higher Stroop interference score, showed higher local EIH (r=0.33; [0.10; 0.53], p=0.007, BF01=0.29). No associations were observed between pain sensitivity and any of the cognitive inhibition performance parameters. The present findings do not support previous evidence on positive associations between exercise-induced hypoalgesia and cognitive inhibition, as well as baseline pain sensitivity and cognitive inhibition.

Remote muscle priming anodal transcranial direct current stimulation attenuates short interval intracortical inhibition and increases time to task failure of a constant workload cycling exercise.

Anodal transcranial direct current stimulation (atDCS), a non-invasive neuromodulatory technique has been shown to increase the excitability of targeted brain area and influence endurance exercise performance. However, the effect of atDCS applied on an unexercised muscle motor cortex (M1) representation on GABAA-mediated intracortical inhibition and endurance exercise performance remains unknown. In two separate sessions, twelve subjects performed fatigue cycling exercise (80% peak power output) sustained to task failure in a double-blinded design, following either ten minutes of bicephalic anodal tDCS (atDCS) or sham applied on a non-exercised hand muscle M1representation. Short interval intracortical inhibition (SICI) wasmeasured at baseline, post neuromodulation and post-exercise using paired-pulse transcranial magnetic stimulation (TMS) in a resting hand muscle. There was a greater decrease in SICI (P < 0.05) post fatigue cycling with atDCS priming compared to sham. Time to task failure (TTF) was significantly increased following atDCS compared to sham (P < 0.05). These findings suggest that atDCS applied over the non-exercised muscle M1representation can augment cycling exercise performance; and although this outcome may be mediated via a multitude of mechanisms, a decrease in the global excitability of GABAA inhibitory interneurons may be a possible contributing factor.

Non-local Muscle Fatigue Effects on Muscle Strength, Power, and Endurance in Healthy Individuals: A Systematic Review with Meta-analysis.

The fatigue of a muscle or muscle group can produce global responses to a variety of systems (i.e., cardiovascular, endocrine, and others). There are also reported strength and endurance impairments of non-exercised muscles following the fatigue of another muscle; however, the literature is inconsistent. To examine whether non-local muscle fatigue (NLMF) occurs following the performance of a fatiguing bout of exercise of a different muscle(s). Systematic review and meta-analysis. A systematic literature search using a Boolean search strategy was conducted with PubMed, SPORTDiscus, Web of Science, and Google Scholar in April 2020, and was supplemented with additional 'snowballing' searches up to September 2020. To be included in our analysis, studies had to include at least one intentional performance measure (i.e., strength, endurance, or power), which if reduced could be considered evidence of muscle fatigue, and also had to include the implementation of a fatiguing protocol to a location (i.e., limb or limbs) that differed to those for which performance was measured. We excluded studies that measured only mechanistic variables such as electromyographic activity, or spinal/supraspinal excitability. After search and screening, 52 studies were eligible for inclusion including 57 groups of participants (median sample = 11) and a total of 303 participants. The main multilevel meta-analysis model including all effects sizes (278 across 50 clusters [median = 4, range = 1 to 18 effects per cluster) revealed a trivial point estimate with high precision for the interval estimate [- 0.02 (95% CIs = - 0.14 to 0.09)], yet with substantial heterogeneity (Q(277) = 642.3, p < 0.01), I2 = 67.4%). Subgroup and meta-regression analyses showed that NLMF effects were not moderated by study design (between vs. within-participant), homologous vs. heterologous effects, upper or lower body effects, participant training status, sex, age, the time of post-fatigue protocol measurement, or the severity of the fatigue protocol. However, there did appear to be an effect of type of outcome measure where both strength [0.11 (95% CIs = 0.01-0.21)] and power outcomes had trivial effects [- 0.01 (95% CIs = - 0.24 to 0.22)], whereas endurance outcomes showed moderate albeit imprecise effects [- 0.54 (95% CIs = - 0.95 to - 0.14)]. Overall, the findings do not support the existence of a general NLMF effect; however, when examining specific types of performance outcomes, there may be an effect specifically upon endurance-based outcomes (i.e., time to task failure). However, there are relatively fewer studies that have examined endurance effects or mechanisms explaining this possible effect, in addition to fewer studies including women or younger and older participants, and considering causal effects of prior training history through the use of longitudinal intervention study designs. Thus, it seems pertinent that future research on NLMF effects should be redirected towards these still relatively unexplored areas.

Lack of Evidence for Non-Local Muscle Fatigue and Performance Enhancement in Young Adults.

Post-activation performance enhancement (PAPE) is an improvement to voluntary muscle performance following a conditioning activity. There is evidence of fatigue resistance deficits in non-exercised muscles following unilateral fatiguing exercise of a contralateral muscle. The purpose of this study was to determine if a unilateral conditioning exercise protocol could induce PAPE in a contralateral, non-exercised muscle in young healthy adults. Thirty-two recreationally trained (n = 16) and athletically trained (n = 16) participants (16 males; age: 22.9 ± 2.03 years; height: 1.81 ± 0.06 m; weight: 82.8 ± 9.43 kg, and 16 females; age: 23.1 ± 2.80 years; height: 1.67 ± 0.07 m; weight: 66.4 ± 11.09 kg) were randomly allocated into two groups (dominant or non-dominant limb intervention). The experimental intervention, involved a conditioning exercise (4-repetitions of 5-seconds knee extension maximal voluntary isometric contractions: MVIC) with either the dominant (DOM) (n = 16) or non-dominant (ND) (n = 16) knee extensors with testing of the same (exercised) or contralateral (non-exercised) leg as well as a control (no conditioning exercise: n = 32) condition. Testing was performed before, 1-minute and 10-minutes after a high intensity, low volume, conditioning protocol (2 sets of 2x5-s MVIC). Pre- and post-testing included MVIC force and F100 (force developed in the first 100 ms: a proxy measure of rate of force development) and unilateral drop jump (DJ) height and contact time. There were no significant MVIC peak force or EMG nor DJ height or contact time interactions (intervention x limb dominance x time). The pre-test (0.50 ± 0.13) dominant leg MVIC F100 forces exceeded (p = 0.02) both post-test and post-10 min by a small magnitude 8.7% (d = 0.31). There was also a significant (p = 0.02) time x intervention leg x testing leg intervention, although it was observed that the control condition was as likely to demonstrate small to large magnitude changes as were the dominant and non-dominant legs. Following the conditioning activity, there was no significant evidence for non-local improvements (PAPE), or performance decreases.

Non-local acute stretching effects on strength performance in healthy young adults.

Static stretching (SS) can impair performance and increase range of motion of a non-exercised or non-stretched muscle, respectively. An underdeveloped research area is the effect of unilateral stretching on non-local force output. The objective of this review was to describe the effects of unilateral SS on contralateral, non-stretched, muscle force and identify gaps in the literature. A systematic literature search following preferred reporting items for systematic review and meta-analyses Protocols guidelines was performed according to prescribed inclusion and exclusion criteria. Weighted means and ranges highlighted the non-local force output response to unilateral stretching. The physiotherapy evidence database scale was used to assess study risk of bias and methodological quality. Unilateral stretching protocols from six studies involved 6.3 ± 2 repetitions of 36.3 ± 7.4s with 19.3 ± 5.7s recovery between stretches. The mean stretch-induced force deficits exhibited small magnitude effect sizes for both the stretched (-6.7 ± 7.1%, d = -0.35: 0.01 to -1.8) and contralateral, non-stretched, muscles (-4.0 ± 4.9%, d = , 0.22: 0.08 to 1.1). Control measures exhibited trivial deficits. The limited literature examining non-local effects of prolonged SS revealed that both the stretched and contralateral, non-stretched, limbs of young adults demonstrate small magnitude force deficits. However, the frequency of studies with these effects were similar with three measures demonstrating deficits, and four measures showing trivial changes. These results highlight the possible global (non-local) effects of prolonged SS. Further research should investigate effects of lower intensity stretching, upper versus lower body stretching, different age groups, incorporate full warm-ups, and identify predominant mechanisms among others.

Quantitative Assessment of Blood Lactate in Shock: Measure of Hypoxia or Beneficial Energy Source.

Blood lactate concentration predicts mortality in critically ill patients and is clinically used in the diagnosis, grading of severity, and monitoring response to therapy of septic shock. This paper summarizes available quantitative data to provide the first comprehensive description and critique of the accepted concepts of the physiology of lactate in health and shock, with particular emphasis on the controversy of whether lactate release is simply a manifestation of tissue hypoxia versus a purposeful transfer (“shuttle”) of lactate between tissues. Basic issues discussed include (1) effect of nonproductive lactate-pyruvate exchange that artifactually enhances flux measurements obtained with labeled lactate, (2) heterogeneous tissue oxygen partial pressure (Krogh model) and potential for unrecognized hypoxia that exists in all tissues, and (3) pathophysiology that distinguishes septic from other forms of shock. Our analysis suggests that due to exchange artifacts, the turnover rate of lactate and the lactate clearance are only about 60% of the values of 1.05 mmol/min/70 kg and 1.5 L/min/70 kg, respectively, determined from the standard tracer kinetics. Lactate turnover reflects lactate release primarily from muscle, gut, adipose, and erythrocytes and uptake by the liver and kidney, primarily for the purpose of energy production (TCA cycle) while the remainder is used for gluconeogenesis (Cori cycle). The well-studied physiology of exercise-induced hyperlactatemia demonstrates massive release from the contracting muscle accompanied by an increased lactate clearance that may occur in recovering nonexercising muscle as well as the liver. The very limited data on lactate kinetics in shock patients suggests that hyperlactatemia reflects both decreased clearance and increased production, possibly primarily in the gut. Our analysis of available data in health and shock suggests that the conventional concept of tissue hypoxia can account for most blood lactate findings and there is no need to implicate a purposeful production of lactate for export to other organs.

The influence of an acute bout of moderate-intensity cycling exercise on sensorimotor integration.

Acute cycling exercise can modulate motor cortical circuitry in the non-exercised upper-limb. Within the primary motor cortex, measures of intracortical inhibition are reduced and intracortical facilitation is enhanced following acute exercise. Further, acute cycling exercise decreases interhemispheric inhibition between the motor cortices and lowers cerebellar-to-motor cortex inhibition. Yet, investigations into the effects of acute exercise on sensorimotor integration, referring to the transfer of incoming afferent information from the primary somatosensory cortex to motor cortex, are lacking. The current work addresses this gap in knowledge with two experimental sessions. In the first session, we tested the exercise-induced changes in somatosensory and motor excitability by assessing somatosensory (SEP) and motor evoked potentials (MEPs). In the second session, we explored the effects of acute cycling exercise on short- (SAI) and long-latency afferent inhibition (LAI), and afferent facilitation. In both experimental sessions, neurophysiological measures were obtained from the non-exercised upper-limb muscle, tested at two time points pre-exercise separated by a 25-min period of rest. Next, a 25-min bout of moderate-intensity lower-limb cycling was performed with measures assessed at two time points post-exercise. Acute lower-limb cycling increased LAI, without modulation of SAI or afferent facilitation. Further, there were no exercise-induced changes to SEP or MEP amplitudes. Together, these results suggest that acute exercise has unique effects on sensorimotor integration, which are not accompanied by concurrent changes in somatosensory or motor cortical excitability.

NEUOPHYSIOLOGICAL CHANGES AFTER UPPER AND LOWER LIMB GRADED EXERCISE TESTING.

Aerobic exercise, including graded exercise testing (GXT), may cause neurophysiological changes of circuits in the primary motor cortex (M1) related to mechanisms of fatigue and/or plasticity. Investigating M1 inhibitory circuit changes over time in exercising compared to non-exercising muscles after GXT of the upper limbs (UL) and lower limbs (LL) may distinguish between different post-exercise mechanisms. PURPOSE: To evaluate M1 inhibitory circuit changes resulting from UL and LL GXT and determine their associations with fitness. METHODS: Six healthy subjects (30 ± 6 yrs) participated. Transcranial Magnetic Stimulation (TMS), Peripheral Nerve Stimulation (PNS), and Electromyography (EMG) were used for neurophysiological testing. Gas analysis was performed to evaluate VO2max (UL: 24.2 ± 4.8, LL: 35.1 ± 5.9 mL/kg/min) during GXTs. Surface electrodes were placed over the first dorsal interosseous (FDI) and tibialis anterior (TA) muscles. Measures of M1 and M1-related afferent inhibition included cortical silent period (CSP) and short-latency afferent inhibition (SAI), respectively. SAI inter-stimulus intervals (ISI) between PNS and TMS stimulations were 21-23ms (UL), and 32-35ms (LL). TMS coil orientation (CO) was altered between posterior-anterior (PA) and anterior-posterior (AP) for both measures of CSP and SAI. CSP and SAI were taken 0-45 min (POST1) and 45-90 min (POST2) post-exercise and compared to pre-exercise. Repeated measures ANOVAs were performed to evaluate effects of exercise type, CO, time, and ISI. RESULTS: CSP decreased at POST1 and increased at POST2 in FDI (97.9 ± 1.2% vs. 104.5 ± 2.5%, p < 0.05) with a trend toward significance in TA (99.3 ± 2.5% vs. 103.5 ± 4.9%, p = 0.19). Although SAI was found for the TA at 32ms (p<0.05) and FDI at 21-23ms (p < 0.05), the interaction of exercise type, CO, and ISI did not reach significance after Huynh-Feldt correction (FDI: p = 0.10, TA: p = 0.10). Univariate linear regression of VO2max and SAI revealed a potential relationship reliant on exercise type and CO (UL: R2 = 0.91, LL: R2 = 0.68). CONCLUSIONS: Changes in CSP suggest that exercise may cause early disinhibition followed by greater inhibition in M1 while changes in SAI may be influenced by fitness levels. Collectively, the results support UL and LL GXTs cause measurable M1 neurophysiological changes.

Power of Words: Influence of Preexercise Information on Hypoalgesia after Exercise—Randomized Controlled Trial

Exercise increases pressure pain thresholds (PPT) in pain-free individuals, known as exercise-induced hypoalgesia (EIH). Positive preexercise information can elicit higher EIH responses, but the effect of positive versus negative preexercise information on EIH is unknown. The primary aim of this randomized controlled trial was to compare EIH at the exercising thigh muscle after an isometric squat exercise between individuals receiving positive versus negative preexercise information about the effect of exercise on pain. Secondary aims were to compare EIH at nonexercising muscles between groups, and to investigate the relationship between participants' expectations and EIH. Eighty-three participants were randomly assigned to brief positive (n = 28), neutral (n = 28) or negative (n = 27) verbal information. The neutral information group was included in the study as a reference group. Pressure pain thresholds at the thigh and trapezius muscles were assessed before and after the intervention (i.e., preexercise information+squat exercise). Expectations of pain relief were assessed using a numerical rating scale (-10 [most negative] to 10 [most positive]). Change in quadriceps and trapezius PPT after the squat exercise showed a large difference between the positive and negative information groups (quadriceps, 102 kPa; 95% confidence interval, 55-150; effect size, 1.2; trapezius, 41 kPa; 95% confidence interval, 16-65; effect size:, 0.9). The positive information group had a 22% increase in quadriceps PPT whereas the negative information group had a 4% decrease. A positive correlation was found between expectations and increase in PPT. Negative preexercise information caused hyperalgesia after the wall squat exercise, whereas positive or neutral preexercise information caused hypoalgesia. Positive preexercise information did not change the magnitude of EIH compared with neutral information.

The effect of blood flow restriction exercise on exercise-induced hypoalgesia and endogenous opioid and endocannabinoid mechanisms of pain modulation.

This study aimed to investigate and compare the magnitude of exercise-induced hypoalgesia (EIH) with low-intensity blood flow restriction (BFR) resistance exercise (RE) at varying pressures to other intensities of resistance exercise and examine endogenous mechanisms of pain reduction. Twelve individuals performed four experimental trials involving unilateral leg press exercise in a randomized crossover design: low-load RE at 30% of one repetition maximum (1RM), high-load RE (70% 1RM), and BFR-RE (30% 1RM) at a low and high pressure. BFR pressure was prescribed relative to limb occlusion pressure at 40% and 80% for the low- and high-pressure trials. Pressure pain thresholds (PPT) were assessed before and 5 min and 24 h following exercise in exercising and nonexercising muscles. Venous blood samples were collected at the same timepoints to determine plasma concentrations of beta-endorphin and 2-arachidonoylglycerol. High-pressure BFR-RE increased PPTs in the exercising limb to a greater extent than all other trials. Comparable systemic EIH effects were observed with HLRE and both BFR-RE trials. PPTs in the exercising limb remained elevated above baseline at 24 h postexercise following both BFR-RE trials. Postexercise plasma beta-endorphin concentration was elevated during the BFR-RE trials. No changes to 2-arachidonoylglycerol concentration were observed. High pressure BFR-RE causes a greater EIH response in the exercising limb that persists for up to 24 h following exercise. The reduction in pain sensitivity with BFR-RE is partly driven by endogenous opioid production of beta-endorphin. BFR-RE should be investigated as a possible pain-modulation tool in individuals with acute and chronic pain.NEW & NOTEWORTHY High-pressure blood flow restriction (BFR) causes a greater hypoalgesia response in the exercising limb (48%) compared with light and heavy load resistance exercise (10-34%). Performing light load resistance exercise with BFR causes systemic hypoalgesia comparable with heavy load resistance exercise (10-18%). BFR resistance exercise prolonged the exercise-induced hypoalgesia response for 24 h in the exercising limb (15% and 24%, respectively). Activation of endogenous opioid production and a conditioned pain modulation effect partly mediate the relationship between exercise and hypoalgesia.

A Single Bout of One-Legged Exercise to Local Exhaustion Decreases Insulin Action in Nonexercised Muscle Leading to Decreased Whole-Body Insulin Action.

A single bout of exercise enhances insulin action in the exercised muscle. However, not all human studies find that this translates into increased whole-body insulin action, suggesting that insulin action in rested muscle or other organs may be decreased by exercise. To investigate this, eight healthy men underwent a euglycemic-hyperinsulinemic clamp on 2 separate days: one day with prior one-legged knee-extensor exercise to local exhaustion (∼2.5 h) and another day without exercise. Whole-body glucose disposal was ∼18% lower on the exercise day as compared with the resting day due to decreased (∼37%) insulin-stimulated glucose uptake in the nonexercised muscle. Insulin signaling at the level of Akt2 was impaired in the nonexercised muscle on the exercise day, suggesting that decreased insulin action in nonexercised muscle may reduce GLUT4 translocation in response to insulin. Thus, the effect of a single bout of exercise on whole-body insulin action depends on the balance between local effects increasing and systemic effects decreasing insulin action. Physiologically, this mechanism may serve to direct glucose into the muscles in need of glycogen replenishment. For insulin-treated patients, this complex relationship may explain the difficulties in predicting the adequate insulin dose for maintaining glucose homeostasis following physical activity.