Bout Of Exhaustive Exercise Research Articles

Response of Circulating Free Cellular DNA to Repeated Exercise in Men with Type 1 Diabetes Mellitus

Background: Intense exercise leads to neutrophil extracellular traps (NETs) formation, which triggers cell disintegration. NET, as well as other processes of apoptosis, necrosis, and spontaneous secretion, result in increased levels of cell-free DNA (cf-DNA) in the circulation. An increment of cf-DNA is also observed in autoimmune diseases, such as type 1 diabetes mellitus (T1DM). Repeated exhaustive exercises are an impulse for physiological adaptation; therefore, in this case–control study, we compared the exercise-induced increase in cf-DNA in men with T1DM and healthy controls to determine the development of the tolerance to exercise. Methods: Volunteers performed a treadmill run to exhaustion at a speed matching 70% of their personal VO2 max at three consecutive visits, separated by a 72 h resting period. Blood was collected before and after exercise for the determination of plasma cell-free nuclear and mitochondrial DNA (cf n-DNA, cf mt-DNA) by real-time PCR, blood cell count and metabolic markers. Results: Each bout of exhaustive exercise induced a great elevation of cf n-DNA levels. An increase in cf mt-DNA was observed after each run. However, the significance of the increase was noted only after the second bout in T1DM participants (p < 0.02). Changes in cf-DNA concentration were transient and returned to baseline values during 72 h of resting. The exercise-induced increment in circulating cf n-DNA and cf mt-DNA was not significantly different between the studied groups (p > 0.05). Conclusions: Cf-DNA appears to be a sensitive marker of inflammation, with a lower post-exercise increase in individuals with T1DM than in healthy men.

Effects of Exhaustive Exercise on Adiponectin and High-Molecular-Weight Oligomer Levels in Male Amateur Athletes.

Physical activity promotes metabolic health and prevents lifestyle-related diseases. Adiponectin is specifically produced by adipose tissue and comes in three forms, differing in terms of weight: trimers (LMW), hexamers (MMW), and high-molecular-weight (HMW) oligomers. The oligomers are associated with the beneficial effects of adiponectin. In this study, we aimed to investigate the impact of a single bout of exhaustive exercise on adiponectin expression in 25 male amateur athletes, divided into two groups, one comprising young adults (YAs) (n = 15), and the other comprising middle-aged adults (MAs) (n = 10). Body fat was estimated through skinfold thickness. Adiponectin levels were assessed at baseline and at 15 min and 24 h post-exercise, while HMW oligomer levels were evaluated at baseline and at 24 h post-exercise. We observed a significant increase in total adiponectin at both 15 min and 24 h after exercise, with there being a more evident effect among the YA subjects. HMW oligomers also increased significantly after exercise both in the total sample and among the YA subjects, but this was not the case in the MA subjects. The increase in adiponectin levels was significantly associated with Powerpeak. Furthermore, a significant inverse correlation was found between basal adiponectin and VO2peak and Powerpeak. In conclusion, a single bout of exhaustive exercise can rapidly and significantly enhance the basal circulating adiponectin concentration, which seems to be negatively associated with maximal aerobic capacity.

Regulation of the mitochondrial integrated stress response and ATF4 by acute contractile activity in mouse muscle

In the context of energetically demanding conditions, such as exercise, skeletal muscle relies on mitochondria to support its metabolic requirements. Maintenance of mitochondria and their bioenergetic availability is thus critical to sustain the metabolic flexibility of muscle. The quality of the organelle network is highly regulated by the coordination of mitochondrial quality control (MQC) processes. One MQC pathway that has garnered recent interest is the integrated stress response (ISR), which is activated in response to a variety of stimuli. The transcription factor ATF4, denoted as the main effector of this response pathway, serves to ameliorate cellular stress by upregulating a plethora of cytoprotective genes, such as CHOP and ATF5. Current literature has shown that the ISR is activated upon mitochondrial stress/perturbations to restore optimal organelle function and health. However, the precise mechanism that constitutes the activation of ISR and thus the response of ATF4 following acute exercise-induced stress is unknown. Therefore, our objective is to determine the extent of ISR/ATF4 induction in vivo and to test whether this pathway is required for the maintenance of muscle function. To investigate this, a mouse in situ hindlimb protocol was utilized to acutely stimulate muscles at 0.25-1 tetani/per second for 9 mins, followed by a 1-hour recovery period. The kinases, CAMKIIα and JNK2, were robustly phosphorylated/activated 6-fold immediately following the protocol. The initial stage of ISR activation, reflected in the ratio of phosphorylated to total-eIF2α protein levels, was also increased in response to acute contractile activity, evident in the recovery phase. Downstream of ISR activation, the total protein expression of ATF4 remained unchanged, however, contractile activity induced an increase in the localization of ATF4 to the nucleus. Robust 2-fold increases in the mRNA expression of ATF4 and CHOP were also observed and enhanced following the recovery period. Changes in ATF4 mRNA appeared to be independent of transcriptional activation, as assessed using an ATF4 promoter-reporter plasmid. An in vitro cell free mRNA decay assay revealed an increase in ATF4 mRNA stability post-stimulation, possibly as a result of cellular compartmental changes in the RNA binding proteins, HuR and CUGBP1. RNA sequencing analyses also confirmed the observed increase in related ISR genes following an exhaustive bout of exercise. These data suggest that acute contractile activity is indeed suffcient to induce mitochondrial stress and activate the ISR, corresponding to the induction of ATF4. Future work will reveal the underlying mitochondrial signal responsible for activating this pathway, as well as the downstream consequences for the regulation of MQC processes in maintaining mitochondrial homeostasis. This work was supported by funds from the Canadian Institutes for Health Research (CIHR). Victoria C. Sanfrancesco is the recipient of the CIHR Frederick Banting and Charles Best Canada Graduate Scholarship-Master's (CGS-M). David A. Hood is the holder of a Canadian Research Chair in Cell Physiology. 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.

Influence of modified starches on mental performance and physical activity following an exhaustive bout of exercise.

Slow-releasing carbohydrates may delay the effects of fatigue after exhaustive exercise. The purpose of this study was to observe the influence that hydrothermally modified starches (HMS) and traditional maltodextrin (MAL) supplements had on physical endurance and mental performance following exhaustive exercise. Male participants completed a VO2 max and 2 days of cycling sessions using a Velotron ergometer. Cycling sessions were performed at 70% of the VO2 max workload for 150 min. Supplements were consumed 30 min before cycling and during exercise at the 120-min mark (1 g CHO/kg body weight). Brain activity was measured using a Neuroscan 64-channel electroencephalogram cap. Go-no-go and N-back tasks were performed before and after cycling bouts. Blood glucose, lactate, ketones, and urine-specific gravity were measured before, during, and after cycling. VO2 and rate of perceived exertion were recorded in 15-min intervals. Ketones increased significantly more for HMS than MAL from pre- to postcycling measurements (p < 0.05). Reaction times for go-no-go and N-back were faster for HMS postexercise. Event-related potential differences were present in both mental tasks following exhaustive exercise. HMS supplementation decreased the impact of cognitive and physical fatigue postexercise.

34 Successive Bouts of Exercise Influences the Inflammatory Cytokine Response in Thoroughbred Horses Regardless of Recovery Aid Supplementation

Abstract In equine sports, the rate of recovery after an exhaustive exercise session greatly affects the ability of the animal to perform subsequently, especially if the next exercise session occurs quickly. Carnitine participates in fatty acid delivery to the mitochondria and may facilitate muscle recovery post-exercise. The objective of the study was to determine the effects of a commercially available carnitine supplement (Renew, Platinum Performance, Buellton, CA) on adult The ability of Thoroughbred horses (16 geldings, 2 mares, 6.69 ± 0.49 years, 524.81 ± 10.07 kg, 5.66 ± 0.12 BCS) to perform successive bouts of exhaustive exercise. All horses participated in a moderate workload conditioning program for 6-weeks before testing. Horses received a ration of applesauce (30 mL, CON, n = 8) or ration of applesauce containing 19.6 g of the product (30 mL, AID, n = 8) 1 h before performing an incremental standardized exercise test (iSET) to exhaustion (day 1). Heart rate (HR) and gait biomechanics were recorded throughout the duration of the iSET. Blood was collected at 0, 10 min, 1, 4 and 6 h relative to exercise for the measurement of lactate and interleukin (IL) 1b, 8 and 10 mRNA content. for the measurement of lactate and interleukin (IL) 1b, IL8 and IL10 mRNA content. The AID was administered again at 1 h post-iSET after collection of the blood sample. All horses were rested for 24 h before repeating the iSET (day 3) with performance data and sample collection. The AID did not affect time to maximum HR, time to reach V200 or total gallop time during the iSET on day 1 or day 3. The rate of HR decline post iSET was slower (P &amp;lt; 0.05) for all horses on day 3 compared with day 1. Blood lactate concentration was not affected by AID or day. The right front limb posterior fetlock angle at full stance phase increased (P &amp;lt; 0.05) with speed for both CON and AID supplemented horses on day 1. Horses receiving AID demonstrated an increase (P &amp;lt; 0.05) in this measure at day 3 while no significant differences (P &amp;gt; 0.05) in posterior angle were detected in CON. Administration of AID did not affect whole blood IL1b, IL8 or IL10 mRNA content on day 1 or day 3. Consolidation of the data demonstrates increased (P &amp;lt; 0.05) expression of IL1b and IL8 mRNA during post-exercise recovery time on day 1 that was absent on day 3. Expression of IL10 was altered (P &amp;lt; 0.05) over time post-exercise on both days. Results of the experiment demonstrate that successive bouts of exercise affect the inflammatory response to exhaustion. Although AID did not affect IL gene expression, it did promote retention of flexion at the fetlock joint suggesting that carnitine products may facilitate recovery from strenuous exercise.

A Carnitine-Containing Product Improves Aspects of Post-Exercise Recovery in Adult Horses.

Strenuous exercise can cause tissue damage, leading to an extended recovery period. To counteract delayed post-exercise recovery, a commercial product containing L-carnitine (AID) was tested in adult horses performing consecutive exercise tests to exhaustion. Fit Thoroughbreds were administered an oral bolus of placebo (CON) or AID prior to performing an exercise test to exhaustion (D1). The heart rate (HR) and fetlock kinematics were captured throughout the exercise test. Blood was collected before, 10 min and 1, 4 and 6 h relative to exercise for the quantification of cytokine (IL1β, IL8, IL10, TNFa) gene expression and lactate concentration. Horses performed a second exercise test 48 h later (D2), with all biochemical and physiological measures repeated. The results demonstrate that the horses receiving AID retained a greater (p < 0.05) amount of flexion in the front fetlock on D2 than the horses given CON. The horses presented a reduced (p < 0.05) rate of HR decline on D2 compared to that on D1. The expression of IL1β, IL8 and IL10 increased at 1 h post-exercise on D1 and returned to baseline by 6 h; the cytokine expression pattern was not duplicated on D2. These results provide evidence of disrupted cytokine expression, HR recovery and joint mobility in response to consecutive bouts of exhaustive exercise. Importantly, AID may accelerate recovery through an undetermined mechanism.

Glucose 6-P Dehydrogenase-An Antioxidant Enzyme with Regulatory Functions in Skeletal Muscle during Exercise.

Hypomorphic Glucose 6-P dehydrogenase (G6PD) alleles, which cause G6PD deficiency, affect around one in twenty people worldwide. The high incidence of G6PD deficiency may reflect an evolutionary adaptation to the widespread prevalence of malaria, as G6PD-deficient red blood cells (RBCs) are hostile to the malaria parasites that infect humans. Although medical interest in this enzyme deficiency has been mainly focused on RBCs, more recent evidence suggests that there are broader implications for G6PD deficiency in health, including in skeletal muscle diseases. G6PD catalyzes the rate-limiting step in the pentose phosphate pathway (PPP), which provides the precursors of nucleotide synthesis for DNA replication as well as reduced nicotinamide adenine dinucleotide phosphate (NADPH). NADPH is involved in the detoxification of cellular reactive oxygen species (ROS) and de novo lipid synthesis. An association between increased PPP activity and the stimulation of cell growth has been reported in different tissues including the skeletal muscle, liver, and kidney. PPP activity is increased in skeletal muscle during embryogenesis, denervation, ischemia, mechanical overload, the injection of myonecrotic agents, and physical exercise. In fact, the highest relative increase in the activity of skeletal muscle enzymes after one bout of exhaustive exercise is that of G6PD, suggesting that the activation of the PPP occurs in skeletal muscle to provide substrates for muscle repair. The age-associated loss in muscle mass and strength leads to a decrease in G6PD activity and protein content in skeletal muscle. G6PD overexpression in Drosophila Melanogaster and mice protects against metabolic stress, oxidative damage, and age-associated functional decline, and results in an extended median lifespan. This review discusses whether the well-known positive effects of exercise training in skeletal muscle are mediated through an increase in G6PD.

The effect of exercise on cytokine concentration in equine autologous conditioned serum.

Autologous conditioned serum (ACS) is a commonly administered intra-articular treatment for the management of osteoarthritis in athletic horses. To investigate the influence of exercise on the concentration of cytokines in a non-commercial method of ACS production. Non-randomised cross over design. Whole blood was obtained from eight healthy Standardbred horses immediately prior to, 1h and 24 h following a single bout of exhaustive exercise. Blood was processed using a non-commercial method of ACS production. Fluorescent microsphere immunoassay (FMIA) analysis was performed to quantify Interleukin 1 receptor antagonist (IL-1Ra), Interleukin-10 (IL-10), Interleukin 1β (IL-1β) and tumour necrosis factor α (TNF-α) concentrations at each time point. Mixed effect repeated measures analysis of variance (ANOVA) was used to compare the pre-exercise and post-exercise cytokine concentrations. Significance was set at P < 0.05. A reduced concentration of IL-1Ra (median 584.4, IQR 81.9-5098 pg/ml, p= 0.004) and an increased concentration of TNF-α (11.92, 9.28-39.75 pg/ml, P= .05) at 1h post-exercise were observed when compared with baseline values (IL-Ra 7349, 1272-10760 pg/ml; TNF TNF-α 11.16, 8.36-32.74 pg/ml). No difference in cytokine concentrations of IL-10 or IL-1β were found between any of the time points. The large biological variability and small sample size represents limitations of this study. These results suggest that a single bout of intense exercise can reduce the concentration of the anti-inflammatory cytokine IL-1Ra and increase the concentration of the pro-inflammatory cytokine TNF-α, reducing the 'anti-inflammatory' cytokine composition of ACS. Our findings suggest that collection of blood for ACS production should be performed no sooner than 24 h following a single episode of intense exercise.

Effect of PKC inhibitor on renal podocyte slit diaphragm protein expression in exhausted rats

Objective: To investigate the expression level of podocyte slit diaphragm protein in rats after one-time exhaustive exercise, to explore the effect of PKC inhibitor on the protein expression level, and to reveal the mechanism of PKC in the formation of exercise-induced proteinuria. Methods: Thirty male SD rats were randomly divided into control group (C), exercise group (E) and exercise combining with PKC inhibitor group (EPI), with 10 rats in each group. Rats in group E and EPI performed one single bout of exhaustive exercise (25 m/min), rats in group EPI were intraperitoneally injected with a PKC inhibitor (chelerythrine, 5 mg/kg) 1 day and 1 hour before exercise respectively, while rats in group C and E were injected with the same volume of saline. Results: ①Compared with group C, the levels of urine protein, uric acid, urine sugar, blood urea, and blood uric acid of rats in group E were increased significantly (P＜0.05), the level of blood glucose was reduced significantly (P＜0.01), and renal ROS production was increased significantly (P＜0.01). The expressions of nephrin and podocin protein in renal tissue were decreased significantly (P＜ 0.05), while the expressions of PKC, Nox2, and Nox4 protein were increased significantly (P＜0.05). ②Compared with group E, the levels of urinary protein,urine glucose and blood urea in EPI group were decreased significantly (P＜0.05), the level of blood glucose was increased significantly (P＜0.01), renal ROS production was reduced significantly (P＜0.01). the expressions of nephrin and podocin protein in renal tissues of the EPI group were increased significantly (P＜0.05), while the expressions of PKC and Nox2 protein was reduced significantly (P＜0.05, P＜0.01). Conclusion: One-time exhaustive exercise can down-regulate the expressions of nephrin and podocin through PKC/Nox/ROS pathways in the kidney of rats; PKC inhibitor alleviates the decrease in the expression of podocyte slit diaphragm protein caused by exhaustive exercise, and prevents the occurrence of exercise-induced proteinuria.

A single bout of exhaustive treadmill exercise increased AMPK activation associated with enhanced autophagy in mice skeletal muscle.

Previous studies reported inconsistent findings on autophagy activation in skeletal muscles after acute exercise. In this study, we investigated the effect of a single bout of exhaustive treadmill exercise on AMPK and autophagy activations in mice gastrocnemius muscle in vivo. Male ICR/CD-1mice were randomly divided into the control and exercise groups. The later was subjected to a single bout of exhaustive treadmill exercise. Changes of AMPK, phosphorylation of AMPKThr172 (pAMPKThr172 ), and autophagy markers including Beclin1, LC3II/LC3I and p62mRNA and protein expressions in gastrocnemius muscle at different times (0, 6, 12, 24h) after the exercise were analysed by quantitative real-time PCR and western blot. Our results demonstrated that a single bout of exhaustive treadmill exercise significantly induced AMPK content and AMPK activity at 0, 6 and 12h after the exercise, and changed the expressions of autophagy markers at different time points in the recovery period, respectively. Moreover, we observed positive correlations between expressions of LC3II/LC3I ratio and pAMPKThr172 or AMPK, and a negative correlation between expressions of p62 and AMPK or pAMPKThr172 . In conclusion, a single bout of exhaustive treadmill exercise in mice caused a prolonged activation of AMPK and improved autophagy in the gastrocnemius muscle. The regulation of autophagic markers were related to enhanced AMPK activity. The findings indicate that acute exercise enhanced AMPK-related autophagy activation may be the underlying molecular mechanism that regulates cellular energy metabolism during exercise.

Effects of acute endurance exercise and exhaustive exercise on innate immune signals induced by mtDNA

Objective: Numerous studies have shown that mitochondrial DNA (mtDNA) can trigger innate immune signaling, and exercise can induce mitochondrial stress. Therefore, this study is aimed at investigating the influence of different types of acute exercise on the innate immune signaling triggered by mtDNA. Methods: Male C57BL/6 mice ( n = 18) were randomly and equally divided into three groups. They were control group, acute moderate-intensity endurance exercise group (AMIE), and 3-day exhaustive exercise group (EE) respectively. Mice were sacrificed immediately after exercise. The spleen, liver, and blood were taken for analysis. Results: The amount of mtDNA in the liver cytoplasm and plasma was significantly decreased after AMIE ( p &lt; .05). However, the amount of mtDNA in plasma was increased after EE (p &lt; .05). The mRNA expression of TFAM, and most TLR9 and cGAS/STING signaling pathway-related genes in the liver and spleen was markedly elevated, whereas the expression of those genes in leukocytes was reduced after AMIE. Furthermore, AMIE significantly decreased the protein expression of NLRP3 inflammasome in the liver ( p &lt; .05) and STING in spleen ( p &lt; .01). Also, AMIE and EE caused a drop in circulating IFN-β levels ( p &lt; .05). Conclusion: A single bout of moderate-intensity exercise reduces mtDNA-induced innate immune signaling and suppresses inflammatory responses by decreasing hepatic cytoplasmic and circulating mtDNA. However, repeated bouts of exhaustive exercise stimulate innate immune signaling by increasing levels of circulating mtDNA.

Excessive Accumulation of Intracellular Ca2+ After Acute Exercise Potentiated Impairment of T-cell Function.

Ca2+ is an important intracellular second messenger known to regulate several cellular functions. This research aimed to investigate the mechanisms of exercise-induced immunosuppression by measuring intracellular calcium levels, Ca2+-regulating gene expression, and agonist-evoked proliferation of murine splenic T lymphocytes. Mice were randomly assigned to the control, sedentary group (C), and three experimental groups, which performed a single bout of intensive and exhaustive treadmill exercise. Murine splenic lymphocytes were separated by density-gradient centrifugation immediately (E0), 3h (E3), and 24h after exercise (E24). Fura-2/AM was used to monitor cytoplasmic free Ca2+ concentration in living cells. The combined method of carboxyfluorescein diacetate succinimidyl ester (CFSE) labeling and flow cytometry was used for the detection of T cell proliferation. The transcriptional level of Ca2+-regulating genes was quantified by using qPCR. Both basal intracellular Ca2+ levels and agonist (ConA, OKT3, or thapsigargin)-induced Ca2+ transients were significantly elevated at E3 group (p<0.05 vs. control). However, mitogen-induced cell proliferation was significantly decreased at E3 group (p<0.05 vs. control). In parallel, the transcriptional level of plasma membrane Ca2+-ATPases (PMCA), sarco/endoplasmic reticulum Ca2+-ATPases (SERCA), TRPC1, and P2X7 was significantly downregulated, and the transcriptional level of IP3R2 and RyR2 was significantly upregulated in E3 (p<0.01 vs. control). In summary, this study demonstrated that acute exercise affected intracellular calcium homeostasis, most likely by enhancing transmembrane Ca2+ influx into cells and by reducing expression of Ca2+-ATPases such as PMCA and SERCA. However, altered Ca2+ signals were not transduced into an enhanced T cell proliferation suggesting other pathways to be responsible for the transient exercise-associated immunosuppression.

The Effect of Anti-Fatigue of mGluR4, GABA-ARα1 and GABA-BR1 on the Substantia Nigra Pars Reticular During Exercise

Objective: The substantia nigra pars reticular (SNR) is the vital nuclei sending out information from basal ganglia and it plays an important part in motor behavior maintenance and motor regulation. It aims to observe the changes of mGluR4，GABA-ARα1 and GABA-BR1 in substantia nigra pars reticular of rats induced by one single bout of exhaustive exercise, and to discuss the relationship among the expression of mGluR4，GABA-ARα1, GABA-BR1 and exercise fatigue. Methods: Thirty-six male wistar rats were divided into three groups at random including CG, 0EG and 90EG,which having 12 rats. Meanwhile, peripheral blood samples were drawn from the vein of tail at different time points (pre- exercise, exercise for 30 min, exercise for 90 min and exhaustion immediately during exercise, and 30 min and 90 min post exercise) ，and blood concentrations of lactic acid (LD) ，blood urea nitrogen (BUN) and activities of creatine kinase (CK) were detected by automatic analyser. Furthermore, the technique of Immunohistochemistry has been used to indicate the protein expression of metabotropic glutamate receptors like mGluR4 and gamma-aminobutyric acid a receptor like GABAAR1, also gamma-aminobutyric acid B receptor like GABAB1. Results: The expression level of mGluR4 in SNR in immediately post-exercise group (0EG) and 90 min post-exercise group (90EG) increase significantly than control group (CG), and the expression level of GABA-ARα1 in SNR at 0EG and 90EG were also significantly higher than control group, and GABA-BR1 in SNR in 0EG and 90EG were both significantly lower than CG. Moreover, it presented significant increases in the levels of LD, BUN and CK in peripheral blood compared with those at rest. Conclusion: Exercise fatigue could result in up-regulation of mGluR4 expression，GABA-ARα1 and down-regulation of GABA-BR1 expression in substantia nigra pars reticular of rats, and it also induce the muscle injury by increase the level of LD, CK and BUN in peripheral blood, which suggested that substantia nigra pars reticular was an important brain rigion to modulate the motor function, and mGluR4，GABA-ARα1 and GABA-BR1 were three important receptors related with the muscle injury induced by exercise fatigue. So the mGluR4, GABA-ARα1 and GABA-BR1 could be the new novel substance produced to prevent from exercise fatigue.

Home-based and personalized endurance training program for patients with mild to moderate hemophilia A: What can be expected?

Some studies suggest that an acute exercise bout can improve the hemostatic process in patients with hemophilia A (HA). No interventional studies have been carried out to assess the influence of endurance training on this effect. We aimed (1) to determine the acceptability of a 6-week personalized endurance training program that HA patients could implement in their daily life and (2) to determine the impact of this endurance training program on endurance capacity and various factors supporting the hemostatic process. Seventeen subjects with mild to moderate HA aged 18 to 45 years were engaged in a home-based and personalized endurance training program (eighteen training sessions, three sessions per week). For each subject, endurance capacity was assessed at inclusion during an exhaustive exercise test coupled with gas exchanges. From this endurance assessment, a personalized interval endurance training plan was drafted and standardized to provide moderate [at the first ventilatory threshold (VT)] to high (at the second VT) metabolic intensity training. At inclusion, the hemostatic process was assessed at rest and after the exhaustive exercise bout. These same tests were repeated after the endurance training program. All 17 patients completed the endurance training program. There were no bleeding-related incidents. Endurance power was increased after the training program (maximal aerobic power: +14%, +0% to +32% for median, minimum and maximum values respectively, P = 0.003; first ventilatory threshold power: +22%, 0% to +100%, P = 0.0006; second ventilatory threshold power: +25%, 0% to +53%, P = 0.0004). In patients with mild HA, endurance training slightly increased FVIII levels when assessed after the maximal exercise bout. Our results support the promotion of a personalized, standardized and home-based exercise prescription for hemophilia patients to improve their cardiorespiratory fitness without negatively influencing the coagulation process. Des études ont suggéré que la réalisation d’un exercice musculaire aigu peut améliorer l’efficacité du processus d’hémostase chez des patients porteurs d’une hémophilie A. Aucune étude interventionnelle n’a jamais été réalisée pour vérifier l’influence d’un entraînement régulier en endurance sur cet effet aigu. Notre étude de type interventionnelle, monocentrique, exploratoire et menée auprès d’un échantillon de patients hémophiles A avait pour objectifs (1) d’évaluer l’acceptabilité de la mise en place au domicile d’un programme d’entraînement en endurance prescrit et personnalisé et (2) de caractériser l’effet de cet entraînement sur les ressources fonctionnelles en endurance et sur le processus hémostatique. Un effectif de 17 patients hémophiles A de sévérité mineure à modérée et âgés de 18 à 45 ans a été recruté. Les ressources fonctionnelles en endurance ont été évaluées à l’inclusion par un test d’exercice musculaire sur bicyclette ergométrique couplé à la mesure des échanges gazeux respiratoires. Cette évaluation a permis de prescrire à chaque patient un programme d’entraînement personnalisé sur bicyclette ergométrique à domicile, à raison de 3 séances par semaine pendant 6 semaines, en créneaux, aux intensités des seuils ventilatoires et codifié via les contrôles de la fréquence cardiaque et de la puissance développée. Un accompagnement téléphonique par un éducateur médico-sportif était proposé au moins une fois par semaine. À l’inclusion, le processus d’hémostase était quantifié au repos et dans les suites immédiates du test d’exercice maximal. À l’issue du programme d’entraînement en endurance, toutes les mesures ont été contrôlées. Les 17 patients ont pu réaliser le programme d’entraînement prescrit. Aucun événement hémorragique n’a été signalé durant la période d’entraînement. À l’issue du programme d’entraînement et en comparaison avec les valeurs mesurées à l’inclusion, la puissance maximale aérobie a augmenté (+14 %, +0 % et +32 % pour respectivement la médiane, le minimum et le maximum ; p = 0,003) de même que les puissances mesurées aux seuils ventilatoires (1 er seuil ventilatoire : +22 %, 0 % et +100 %, p = 0,0006 ; 2 e seuil ventilatoire : +25 %, 0 % et +53 %, p = 0,004). À l’issue du programme d’entraînement, le processus d’hémostase n’a été dégradé chez aucun des patients. Dans le sous-groupe des patients porteurs d’une forme mineure de la maladie, l’entraînement en endurance a légèrement majoré la réponse sécrétoire en facteur VIII induite par la réalisation du test d’exercice d’intensité maximale. Notre étude a permis de vérifier que l’application d’une prescription d’entraînement en endurance à des patients porteurs d’une hémophilie A de sévérité mineure à modérée peut être envisagée au domicile des patients. Cette pratique induit une amélioration de la ressource fonctionnelle en endurance des patients hémophiles A sans modifier le processus d’hémostase.

Circulating biomarkers of nitric oxide bioactivity and impaired muscle vasoreactivity to exercise in adults with uncomplicated type 1 diabetes.

Early compromised endothelial function challenges the ability of individuals with type 1 diabetes to perform normal physical exercise. The exact mechanisms underlying this vascular limitation remain unknown, but may involve either formation or metabolism of nitric oxide (NO), a major vasodilator, whose activity is known to be compromised by oxidative stress. Muscle microvascular reactivity (near-infrared spectroscopy) to an incremental exhaustive bout of exercise was assessed in 22 adults with uncomplicated type 1 diabetes (HbA1c 64.5 ± 15.7mmol/mol; 8.0 ± 1.4%) and in 21 healthy individuals (18-40years of age). NO-related substrates/metabolites were also measured in the blood along with other vasoactive compounds and oxidative stress markers; measurements were taken at rest, at peak exercise and after 15min of recovery. Demographic characteristics, body composition, smoking status and diet were comparable in both groups. Maximal oxygen uptake was impaired in individuals with type 1 diabetes compared with in healthy participants (35.6 ± 7.7 vs 39.6 ± 6.8mlmin-1kg-1, p < 0.01) despite comparable levels of habitual physical activity (moderate to vigorous physical activity by accelerometery, 234.9 ± 160.0 vs 280.1 ± 114.9min/week). Compared with non-diabetic participants, individuals with type 1 diabetes also displayed a blunted exercise-induced vasoreactivity (muscle blood volume at peak exercise as reflected by ∆ total haemoglobin, 2.03 ± 5.82 vs 5.33 ± 5.54μmol/l; interaction 'exercise' × 'group', p < 0.05); this was accompanied by lower K+ concentration (p < 0.05), reduced plasma L-arginine (p < 0.05)-in particular when HbA1c was high (mean estimation: -4.0, p < 0.05)-and lower plasma urate levels (p < 0.01). Nonetheless, exhaustive exercise did not worsen lipid peroxidation or other oxidative stress biomarkers, and erythrocytic enzymatic antioxidant resources were mobilised to a comparable extent in both groups. Nitrite and total nitrosation products, which are potential alternative NO sources, were similarly unaltered. Graphical abstract CONCLUSIONS/INTERPRETATION: Participants with uncomplicated type 1 diabetes displayed reduced availability of L-arginine, the essential substrate for enzymatic nitric oxide synthesis, as well as lower levels of the major plasma antioxidant, urate. Lower urate levels may reflect a defect in the activity of xanthine oxidase, an enzyme capable of producing NO from nitrite under hypoxic conditions. Thus, both canonical and non-canonical NO production may be reduced. However, neither of these changes exacerbated exercise-induced oxidative stress. clinicaltrials.gov NCT02051504.

Repetitive Bouts of Exhaustive Exercise Induces a Systemic Inflammatory Response and Multi-Organ Damage in Rats.

Multiple organ dysfunction syndrome can follow severe infection or injury, but its relationship to exercise is not well understood. Previous studies have observed that prolonged strenuous exercise can lead to transiently increased level and/or activity of markers for systemic inflammatory response and multiple organ damage. However, few studies have analyzed the pathogenesis of the inflammatory response and subsequent multi-organ injury in exhaustive exercise conditions. In this study, we established a rat model of repetitive bouts of exhaustive running (RBER) and investigated its effects on multiple organ damage. Rats were subjected to RBER in either uphill or downhill running modes daily for a period of 7 days. Morphologically, RBER causes tissue structural destruction and infiltration of inflammatory cells in the skeletal muscles and many visceral organs. RBER also causes sustained quantitative changes in leukocytes, erythrocytes, and platelets, and changes in the concentration of blood inflammatory factors. These inflammatory alterations are accompanied by increases in serum enzyme levels/activities which serve as functional markers of organ damage. In general, RBER in the downhill mode seemed to cause more damage evaluated by the above-mentioned measures than that produced in the uphill mode. A period of rest could recover some degree of damage, especially for organs such as the heart and kidneys with strong compensatory capacities. Together, our data suggest that, as a result of multi-organ interactions, RBER could cause a sustained inflammatory response for at least 24 h, resulting in tissue lesion and ultimately multiple organ dysfunction.

Effects of simultaneous intake of chamomile and ibuprofen on delayed-onset muscle soreness markers and some liver enzymes following eccentric exercise

Delayed-onset muscle soreness (DOMS) occurs after intense eccentric contractions or after performing unaccustomed exercise. Chamomile and ibuprofen may prevent or attenuate DOMS symptoms. The aim of this study was to investigate the effects of simultaneous intake of chamomile and ibuprofen on markers of muscle damage, pain, and inflammation after exhaustive eccentric exercise in young men. In a double blind randomized clinical trial, 40 young men participated voluntarily in the study and were randomly and equally assigned to groups including chamomile (Cham; 1600 mg/day), ibuprofen (IBP; 1600 mg/day), chamomile + ibuprofen (Cham-IBP; 800 mg/day ibuprofen and 800 mg/day chamomile), and placebo. Participants performed a bout of exhaustive eccentric exercise following a week of supplementation. Blood samples were collected before the start of supplementation, before the eccentric exercise, 24, 48, and 72 h after the eccentric exercise and aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), and creatine kinase (CK) were measured in the plasma. In addition, muscle soreness, Sargent jump test (SJ), and knee range of motion (ROM) as functional capacity were measured. The results showed that ROM significantly improved 48 h post exercise in all three treatment groups (p ≤ 0.05). Also, chamomile supplementation significantly improved MS, SJ, AST, and ALT more than ibuprofen, and chamomile + ibuprofen compared to the placebo group (p ≤ 0.05). In conclusion, chamomile is more effective than ibuprofen or combination of chamomile and ibuprofen in attenuating muscle soreness after intense muscle-damaging exercise.

Impact of Post-Exercise Fructose-Maltodextrin Ingestion on Subsequent Endurance Performance.

Background: Current sports nutrition guidelines recommend athletes ingest carbohydrates at 1.0–1.2 g·kg−1·h−1 to optimize repletion of muscle glycogen during short-term recovery from endurance exercise. However, they do not provide specific advice on monosaccharides (e.g., fructose or glucose) other than to ingest carbohydrates of moderate to high glycaemic index. Recent evidence suggests that combined ingestion of fructose and glucose in recovery leads to enhanced liver glycogen synthesis and that this translates into improvement of subsequent endurance capacity.Purpose: The purpose of the present study was to investigate whether consuming a combination of fructose and glucose as opposed to glucose alone during short-term recovery (i.e., 4 h) from exhaustive exercise would also improve subsequent pre-loaded cycle time trial (TT) performance.Methods: Eight participants (seven men, one woman; O2peak: 56.8 ± 5.0 mLO2·min−1·kg−1; Wmax: 352 ± 41 W) participated in this randomized double-blind study. Each experimental session involved a glycogen reducing exercise bout in the morning, a 4-h recovery period and 1-h of steady state (SS) exercise at 50% Wmax followed by a ~40-min simulated TT. During recovery carbohydrates were ingested at a rate of 1.2 g·kg−1·h−1 in the form of fructose and maltodextrin (FRU + MD) or dextrose and maltodextrin (GLU + MD) (both in 1:1.5 ratio). Substrate oxidation rates, including ingested carbohydrate oxidation, were determined during the steady state (SS). Blood samples were collected during recovery, during the SS exercise and at the end of the TT for determination of glucose and lactate concentrations.Results: There were no differences in TT performance [37.41 ± 3.45 (GLU + MD); 37.96 ± 5.20 min (FRU + MD), p = 0.547]. During the first 45-min of SS oxidation of ingested carbohydrates was greater in FRU + MD (1.86 ± 0.41 g−1·min−1 and 1.51 ± 0.37 g−1·min−1 for FRU + MD and GLU + MD, respectively; time x condition interaction p = 0.003) and there was a trend toward higher overall carbohydrate oxidation rates in FRU + MD (2.50 ± 0.36 g−1·min−1 and 2.31 ± 0.37 g−1·min−1 for FRU + MD and GLU + MD, respectively; p = 0.08). However, at 60-min of SS, differences in substrate oxidation disappeared.Conclusion: Ingestion of combined fructose and glucose compared to glucose only during recovery from an exhaustive exercise bout increased the ingested carbohydrate oxidation rate during subsequent exercise. Under the conditions studied, subsequent TT performance was not improved with fructose-glucose.

Profiles of Heart Rate Variability and Bar Velocity after Resistance Exercise.

The aim of this investigation was to observe the association in the time course in recovery between multiple heart rate variability (HRV) metrics and neuromuscular performance, as assessed by mean bar velocity (BVM) in the back squat, over a 72-h period after an exhaustive back squat protocol. Eight resistance-trained males completed five laboratory visits within a 7-d period. The first visit involved short-term HRV recordings followed by a familiarization of BVM procedures and a one-repetition maximum test of the back squat. Forty-eight hours later, participants returned to the laboratory for prestimulus measurements, immediately followed by a back squat protocol (8 sets of 10 repetitions at 70% of one-repetition maximum with a 2-min rest). The HRV and the BVM measurements were replicated at 0.5, 24, 48, and 72 h after squat protocol. A multivariate profile analysis and repeated-measures correlation between recovery scores [(new/prestimulus) × 100] for each HRV metric and BVM was computed. All log-transformed (ln) HRV metrics, except low frequency (lnLF) (P = 0.051), had a significant interaction with BVM over time (P < 0.05), indicating that recovery scores in BVM and HRV were not parallel. In addition, recovery scores in all HRV metrics significantly differed from BVM (P < 0.05) in at least one time point across the 72-h period. Furthermore, repeated-measures correlation analysis indicated a lack of intraindividual association (P > 0.05) between the change in BVM and all HRV measurements over time. The time course in recovery in HRV measurements after an exhaustive bout of lower-body resistance exercise was not associated with neuromuscular performance recovery.

Acute Voluntary Wheel Running Attenuates Olanzapine‐Induced Hyperglycemia in Male Mice

BackgroundOlanzapine is a second‐generation antipsychotic often used in the treatment of schizophrenia and other “off‐label” conditions. Though effective in reducing psychoses, the use of olanzapine is associated with adverse metabolic side effects. Acutely, olanzapine increases liver glucose output and the development of insulin resistance. Chronic olanzapine treatment leads to weight gain and predisposes individuals to the development of cardiovascular disease and type 2 diabetes. Exercise is an intervention which helps to maintain glucose homeostasis, and with long‐term adherence, can decrease glucose intolerance and insulin resistance. We have previously demonstrated that a single bout of exhaustive exercise mitigates olanzapine‐induced hyperglycemia. While these findings are encouraging, the clinical relevance of exhaustive exercise in individuals taking olanzapine is limited.Purpose &amp; HypothesesThe purpose of this study was to investigate if increases in short‐term, habitual physical activity in the form of voluntary wheel running (VWR) would have a protective effect against olanzapine‐induced hyperglycemia.Methods10‐week old male C57BL/6J mice remained sedentary or were provided running wheels at the start of the dark cycle (~20:00 h), until the following morning (~8:00 h; start of light cycle). Olanzapine (5 mg/kg body weight (BW)) was administered intraperitoneally (IP) immediately following overnight VWR, or 6 hours and 24 hours post wheel‐lock. Blood glucose was measured at baseline, 30, 60, 90, and 120 mins post‐olanzapine. In parallel experiments following the same overnight VWR protocol, an insulin tolerance test (ITT) (0.5 IU/kg BW; IP) was conducted 60 mins post‐olanzapine treatment to assess olanzapine‐induced insulin resistance among groups.ResultsA single overnight session of VWR protected against acute olanzapine‐induced hyperglycemia immediately post‐wheel lock. This protective effect was still present 6 hours post‐wheel lock, and had reversed by 24 hours after the cessation of exercise. Under insulin‐stimulated conditions, the sedentary olanzapine‐treated mice had significantly higher blood glucose area‐under‐the‐curve compared to the other three groups, providing evidence that a prior bout of VWR protects against olanzapine‐induced insulin resistance. Under insulin‐stimulated conditions, serum free fatty acid concentrations were increased with olanzapine and reduced with VWR.ConclusionsOur findings demonstrate that with a single session of overnight habitual physical activity, olanzapine‐induced hyperglycemia is mitigated for at least 6 hours post‐exercise and insulin‐stimulated glucose disposal is recovered under olanzapine‐treated conditions.Support or Funding InformationThis study was supported by the Canadian Institutes of Health Research.