Exhaustive Exercise Research Articles

Exhaustive stress causes a rapid immunological response in the humoral and cellular haemolymph compartments of the pale octopus (Octopus pallidus)

Cephalopods are economically and ecologically important species across the world, yet information linking physiological stress and associated immunological responses is limited in the current literature. Here, the effects of exhaustive exercise in a holobenthic octopus species, Octopus pallidus, were examined by evaluating immunological parameters. In whole haemolymph, the pH and refractive index were measured. To assess the cellular function of the haemolymph, the total count, cell vitality and phagocytosis capacity of the haemocytes were also measured. To assess enzymatic function, activities of the phenoloxidase system and lysozyme were quantified in the plasma and cellular components of the haemolymph. Overall, exhaustive exercise led to rapid changes in the haemolymph with a significant decrease in the pH and phagocytosis capacity though the number of cells and cell vitality were not affected. Exercise also triggered the increase of activated phenoloxidase (PO-like) activity and the decrease of the inactive zymogen prophenoloxidase (ProPO-like), total PO-like and lysozyme activity in plasma and an increase in total PO-like activity in the hemocyte compartment. These responses indicated that a realistic energetic demand had substantial, rapid impact on immune function. These results also provide an important baseline to understand the immune physiology of cephalopods that will further efforts to identify the mechanisms underlying the impacts of stressors.

Coronary circulation enhances the aerobic performance of wild Pacific salmon.

Female Pacific salmon often experience higher mortality than males during their once-in-a-lifetime up-river spawning migration, particularly when exposed to secondary stressors (e.g. high temperatures). However, the underlying mechanisms remain unknown. One hypothesis is that female Pacific salmon hearts are more oxygen-limited than those of males and are less able to supply oxygen to the body's tissues during this demanding migration. Notably, female hearts have higher coronary blood flow, which could indicate a greater reliance on this oxygen source. Oxygen limitations can develop from naturally occurring coronary blockages (i.e. coronary arteriosclerosis) found in mature salmon hearts. If female hearts rely more heavily on coronary blood flow but experience similar arteriosclerosis levels as males, they will have disproportionately impaired aerobic performance. To test this hypothesis, we measured resting (RMR) and maximum metabolic rate (MMR), aerobic scope (AS) and acute upper thermal tolerance in coho salmon (Oncorhynchus kisutch) with an intact or artificially blocked coronary oxygen supply. We also assessed venous blood oxygen and chemistry (cortisol, ions and metabolite concentrations) at different time intervals during recovery from exhaustive exercise. We found that coronary blockage impaired MMR, AS and the partial pressure of oxygen in venous blood (PvO2) during exercise recovery but did not differ between sexes. Coronary ligation lowered acute upper thermal tolerance by 1.1°C. Although we did not find evidence of enhanced female reliance on coronary supply, our findings highlight the importance of coronary blood supply for mature wild salmon, where migration success may be linked to cardiac performance, particularly during warm water conditions.

Plasma Volume Shifts and Acid–Base Balance After a Single Bout of Resistance Training

Abstract Purpose Changes in plasma volume (PV), acid–base status and ventilation have rarely been investigated in relation to resistance training (RT). This study aimed to investigate the effect of a single set of exhaustive leg press exercise on these basic physiological parameters in an integrated manner. Methods Twenty-seven male individuals (27.1 ± 4.1 years, 1.82 ± 0.62 m, 84.4 ± 12.5 kg, BMI: 25.4 ± 3.0 k/gm2) performed a single set leg press exercise during which hemoglobin concentration ([Hb]), hematocrit (Hct), pH, oxygen (pO2) and carbon dioxide partial pressures (pCO2), hydrogen carbonate concentration ([HCO3−]), standard base excess (SBE) and lactate concentration ([La−]) were determined. Total buffer capacity was calculated based on pH, [HCO3−] and pCO2. Results Mean PV decreased by 559 ± 230 mL (13.7%). As a result, arterial oxygen content was significantly increased due to hemoconcentration (P < 0.001). At exhaustion, pH (7.30 ± 0.06), [HCO3−] (18.6 ± 2.0 mmol/L) and SBE (− 6.6 ± 2.4 mmol/L) were all significantly decreased (P < 0.0001). The pCO2 first remained unchanged (39.4 ± 4.3 mm Hg) but demonstrated a significant decrease one-minute post-exercise (34.4 ± 4.2 mmHg), indicating metabolic acidosis with respiratory compensation, which was maintained until t+15. Non-bicarbonate buffering remained constant during recovery while the respiratory component steadily increased until 15-min post-exercise (50.2 mmol/L per pH). Conclusion PV shifts following a single set of leg press exercise improve post-exercise arterial oxygen content. The moderate metabolic acidosis was not compensated during exercise because of restricted breathing but partly compensated during the following 15-min recovery period. The respiratory compensation as part of the bicarbonate buffering made up 50% of total buffer capacity in the course of recovery.

An alternate to accumulated oxygen deficit (AOD) for measuring anaerobic contribution: 'AOD_alt' is valid in normoxia and hypoxia.

The gold standard measure of anaerobic contribution is accumulated oxygen deficit (AOD). The purpose of this study was to investigate the validity of an alternate measure, AOD_alt. AOD_alt is the sum of the phosphocreatine and glycolytic contributions, which are estimated from post-exercise oxygen uptake and blood lactate concentration, respectively. In Study One, six women and three men performed 6-min bouts of heavy intensity cycle ergometer exercise, once in normoxia (FIO2 ~ 21%) and twice under hypoxic conditions (FIO2 ~ 15% and ~ 12%). In Study Two, four women and two men performed severe intensity tests to exhaustion, once in normoxia (~ 10min) and twice in hypoxia (FIO2 ~ 15% and ~ 10%). Physiological responses were measured during exercise and 7min of recovery. In 6min of heavy exercise, Study One, the alternate and criterion measures of anaerobic contribution (AOD_alt and AOD) were correlated, in normoxia and in hypoxia. In exhaustive severe exercise, Study Two, AOD_alt and AOD were correlated (r = 0.77) and similar, in normoxia and at FIO2 ~ 15%. However, AOD_alt and AOD values were neither correlated (r = 0.27) nor similar (57 ± 5mL·kg-1 vs 51 ± 7mL·kg-1) at FIO2 ~ 10%. These results confirm the validity of AOD_alt as a measure of anaerobic capacity in severe intensity exercise, demonstrate its validity in heavy exercise, and assert its validity in conditions of hypoxia (FIO2 ~ 12%).

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.

Differences In Skeletal Muscle Oxygenation Of Vastus Laterals And Gastrocnemius During Exhaustive Exercise

Differences In Skeletal Muscle Oxygenation Of Vastus Laterals And Gastrocnemius During Exhaustive Exercise

Control parameter optimisation using the evidence framework for the ant colony optimisation algorithm

The ant colony optimization (ACO) algorithm is a metaheuristic initially designed to solve the travelling salesman problem (TSP). The design of experiments, finding the suitable ACO algorithm configuration, and calibrating the adaptive control parameters are exhaustive and time-consuming exercises, especially for TSPs where the number of cities can exceed 1000. This paper presents an evidence framework driven control parameter optimisation (EFCPO) algorithm for an ACO algorithm solving TSPs. EFCPO performs auto-tuning of the adaptive control parameters and makes recommendations about the ACO algorithms that are best suited for the TSPs in question using the log evidence. In addition, with this ability, the algorithm can take a solution provided by an ACO algorithm and improve the results. The EFCPO accomplishes this over a number of cycles through auto-tuning of the control parameters and re-running the ACO until the process is completed. The capabilities of EFCPO are compared to another configuration tool, irace, using benchmark ACO algorithms to test the efficiency of the framework. The benchmark algorithms make use of a local search strategy to solve TSPs. The results show that ACO algorithms are able to find new and improved solution tours within reasonable times. The improvements are also significant. In addition, ACO algorithms that are best suited for the TSP in question are preferred, making the EFCPO an effective tool for real-time configuration of ACO algorithms for solving TSPs .

Apigenin With Protective Effect Against Oxidative Injury to Skeletal Muscle Cells via Activation of the Nrf-2HO-1 Pathway

Human skeletal muscle would suffer from an oxidative injury caused by long-term training or exhaustive exercise. It is important to scavenge oxygen free radicals in due course to reduce oxidative damage to human skeletal muscle cells (HSKMC) by some means. Apigenin, as an effective antioxidant, is likely to protect HSKMC against oxidative injury. In this study, tert-butyl hydroperoxide (t-BHP) was used to induce oxidative injured HSKMC. Then, we studied the protective effect of apigenin on cell viability, oxidative stress status, and the expression of antioxidation-related proteins and tried to understand the mechanisms driving these effects. Results show that the cellular viability of HSKMC could be obviously improved by apigenin treatment at the concentration of 80 μM. Pretreatment with celery resulted in the activity of related enzymes approaching normal levels, and decrease the release of malondialdehyde and the level of intracellular reactive oxygen species in HSKMC. The Nuclear factor E2-related factor (Nrf2) signaling pathway could also be activated by apigenin. Therefore, apigenin could attenuate t-BHP induced oxidative injury in HSKMC through enhancement of the activities of related antioxidant enzymes by activating the Nrf2 pathway.

Comparison of the effects of cold water immersion and percussive massage on the recovery after exhausting eccentric exercise: A three-armed randomized controlled trial.

Athletic training requires both challenging stimuli for adaptation and sufficient recovery for improved performance. While cold water immersion (CWI) is already a popular recovery method, handheld percussive massage (PM) devices have also gained popularity in recent years. This study aims to assess the effects of CWI and PM on performance recovery after strenuous eccentric exercises compared to a passive rest (PR) control condition. Thirty-four healthy physically active participants (9 females, 25 males) were randomly divided into three groups: CWI (n = 11), PM (n = 11), and passive rest (PR) (n = 12). They underwent an exhausting eccentric exercise protocol and different measurements at six time points (baseline, POST1, POST2, POST24, POST48, and POST72) over the time course of 72h. These included subjective assessments of muscle soreness and perceived stiffness as well as measures of skin temperature, leg volume, creatine kinase activity, and three different jump tests. The eccentric exercise protocol consisted of 15min downhill running (slope: 12%, speed: 10km/h) and 3 sets of successive depth jumps (dropping height: 0.5m) until individual exhaustion. After POST1 measurements, participants received 12min of either CWI (11 ± 0.5°C), PM (40Hz) or PR (supine posture). No significant group effects were found for the number of depth jumps performed during the exhaustion protocol. All jump tests displayed a significant group × time interaction effect. Post-hoc analysis indicated significant lower jump heights in ΔPOST2 between CWI and both PM and PR. No other significant group effects were observed at any time point. No significant group × time interaction effects were noted for CK, leg volume, and soreness. The perceived stiffness showed a significant group × time interaction effect. Post-hoc analysis revealed a significant decrease in stiffness for PM compared to PR at ΔPOST2. Neither CWI nor PM showed any significant improvement in performance recovery over the 72-h period following strenuous eccentric exercise compared to PR. CWI showed an immediate performance decline which may be attributed to a cold-related reduction in motor nerve conduction velocity.

Changes in Plasma Concentration of Free Proteinogenic and Non-Proteinogenic Amino Acids in High-Performance Sprinters over a 6-Month Training Cycle.

Background/Objectives: Free amino acids substantially contribute to energy metabolism. Also, their profile may identify (over)training status and effectiveness. The long-term effects of speed-power training on plasma free amino acid (PFAA) profiles are not known. We aimed to observe variations in PFAA levels in high-performance sprinters in a six-month training cycle. Methods: Ten male athletes (24.6 ± 3.3 years) were examined during four training phases: transition (1 month), general preparation (2 months), specific preparation (1 month), and pre-competition/competition (2 months). Venous blood was collected at rest, after exhaustive exercise, and recovery. Forty-two PFAAs were analyzed by the LC-ESI-MS/MS method. Results: Significant decreases in resting concentrations were observed between the transition and competition phases for glutamine (762 ± 117 vs. 623 ± 53 μmol∙L-1; p < 0.001, η2 = 0.47) and histidine (89 ± 15 vs. 75 ± 10 μmol∙L-1; p = 0.010, η2 = 0.27), whereas β-alanine (30 ± 7 vs. 41 ± 9 μmol∙L-1; p = 0.024, η2 = 016) and sarcosine (3.6 ± 0.4 vs. 4.8 ± 0.6 μmol∙L-1; p = 0.006, η2 = 0.188) levels increased. Between the specific and competition phases, significant decreases in the resting levels of 1-methylhistidine (22.1 ± 19.4 vs. 9.6 ± 8.8 μmol∙L-1; p = 0.14, η2 = 0.19), 3-methylhistidine (7.1 ± 1.5 vs. 6.5 ± 1.6 μmol∙L-1; p = 0.009, η2 = 0.18), citrulline (40 ± 10 vs. 29 ± 4 μmol∙L-1; p = 0.05, η2 = 0.29), and ornithine (74 ± 15 vs. 56 ± 10 μmol∙L-1; p = 0.015, η2 = 185) were noticed. Also, for β-alanine and sarcosine, the pattern of response to exercise strongly changed between the training phases. Blood ammonia levels at exhaustion decreased between the transition and competition phases (32 ± 4 vs. 23 ± 5 μmol∙L-1; p < 0.001, η2 = 0.67), while lactate, the phenylalanine-tyrosine ratio, the glutamine-glutamate ratio, hematological parameters, and cardiorespiratory indices remained at similar levels. Conclusions: Speed-power training seems to affect PFAAs involved in skeletal muscle metabolic pathways responsible for neutralizing toxic ammonia (glutamine, arginine, citrulline, ornithine), attenuating the deleterious effects of H+ ions (histidine, β-alanine), and reducing exercise-induced protein breakdown (1- and 3-methylhistidine). Our findings suggest that sprint-oriented training supports metabolic pathways that are responsible for the removal of harmful metabolites produced during exercise.

Influencing factors and physiological parameters of psychological hurdle and motivation immediately prior to exercise.

To obtain the benefits of exercise as physical inactivity becomes a global concern, managing psychological hurdles to exercise implementation is important. This study examined troublesomeness, motivation, and physiological parameters immediately before exhaustive exercise. Thirty-one healthy university students (mean age 19.87±2.21 years, 19 female) performed two conditions on separate days: performing push-ups to exhaustion (PE condition) and performing push-ups of the 30% count of the PE condition (P30 condition). Before the push-ups, the participants sat at rest for 5 minutes and were asked about their psychological states; after the first 2 minutes, PE or P30 conditions to be performed that day were disclosed to prepare them psychologically. During the rest, changes in the heart rate variability (HRV), pupil diameter, and front polar area (FPA) neural activity were measured before and after disclosure. Troublesomeness and FPA neural activities were significantly higher in the PE than in the P30 (P<0.001, P=0.04, P=0.01). Correlation analysis revealed correlations between motivation and pupil diameter (P=0.002), and negative correlations between total physical activity (TPA) and negative image of exercise (P=0.01). FPA activity could reflect the psychological hurdle to exhaustive exercise, pupil diameter could reflect the motivational arousal to exercise, and TPA could modulate the psychological hurdle.

Nitric Oxide Ameliorates the Effects of Hypoxia in Mice by Regulating Oxygen Transport by Hemoglobin.

Xiaoying Zhou, Wenting Su, Quanwei Bao, Yu Cui, Xiaoxu Li, Yidong Yang, Chengzhong Yang, Chengyuan Wang, Li Jiao, Dewei Chen, and Jian Huang. Nitric oxide ameliorates the effects of hypoxia in mice by regulating oxygen transport by hemoglobin. High Alt Med Biol. 25:174-185, 2024.-Hypoxia is a common pathological and physiological phenomenon in ischemia, cancer, and strenuous exercise. Nitric oxide (NO) acts as an endothelium-derived relaxing factor in hypoxic vasodilation and serves as an allosteric regulator of hemoglobin (Hb). However, the ultimate effects of NO on the hematological system invivo remain unknown, especially in extreme environmental hypoxia. Whether NO regulation of the structure of Hb improves oxygen transport remains unclear. Hence, we examined whether NO altered the oxygen affinity of Hb (Hb-O2 affinity) to protect extremely hypoxic mice. Mice were exposed to severe hypoxia with various concentrations of NO, and the survival time, exercise capacity, and other physical indexes were recorded. The survival time was prolonged in the 5 ppm NO (6.09 ± 1.29 minutes) and 10 ppm NO (6.39 ± 1.58 minutes) groups compared with the 0 ppm group (4.98 ± 1.23 minutes). Hypoxia of the brain was relieved, and the exercise exhaustion time was prolonged when mice inhaled 20 ppm NO (24.70 ± 6.87 minutes vs. 20.23 ± 6.51 minutes). In addition, the differences in arterial oxygen saturation (SO2%) (49.64 ± 7.29% vs. 42.90 ± 4.30%) and arteriovenous SO2% difference (25.14 ± 8.95% vs. 18.10 ± 6.90%) obviously increased. In ex vivo experiments, the oxygen equilibrium curve (OEC) left shifted as P50 decreased from 43.77 ± 2.49 mmHg (0 ppm NO) to 40.97 ± 1.40 mmHg (100 ppm NO) and 38.36 ± 2.78 mmHg (200 ppm NO). Furthermore, the Bohr effect of Hb was enhanced by the introduction of 200 ppm NO (-0.72 ± 0.062 vs.-0.65 ± 0.051), possibly allowing Hb to more easily offload oxygen in tissue at lower pH. The crystal structure reveals a greater distance between Asp94β-His146β in nitrosyl -Hb(NO-Hb), NO-HbβCSO93, and S-NitrosoHb(SNO-Hb) compared to tense Hb(T-Hb, 3.7 Å, 4.3 Å, and 5.8 Å respectively, versus 3.5 Å for T-Hb). Moreover, hydrogen bonds were less likely to form, representing a key limitation of relaxed Hb (R-Hb). Upon NO interaction with Hb, hydrogen bonds and salt bridges were less favored, facilitating relaxation. We speculated that NO ameliorated the effects of hypoxia in mice by promoting erythrocyte oxygen loading in the lung and offloading in tissues.

Hypoxia-acclimation adjusts skeletal muscle anaerobic metabolism and burst swim performance in a marine fish

Red drum, Sciaenops ocellatus, are a marine teleost native to the Gulf of Mexico that routinely experiences periods of low oxygen (hypoxia). Recent work has demonstrated this species has the capacity to improve aerobic performance in hypoxia through respiratory acclimation. However, it remains unknown how hypoxia acclimation impacts anaerobic metabolism in red drum, and the consequences of exhaustive exercise and recovery. Juvenile fish were acclimated to normoxia (n = 15, DO 90.4 ± 6.42 %) or hypoxia (n = 15, DO 33.6 ± 7.2 %) for 8 days then sampled at three time points: at rest, after exercise, and after a 3 h recovery period. The resting time point was used to characterize the acclimated phenotype, while the remaining time points demonstrate how this phenotype responds to exhaustive exercise. Whole blood, red muscle, white muscle, and heart tissues were sampled for metabolites and enzyme activity. The resting phenotype was characterized by lower pHe and changes to skeletal muscle ATP. Exhaustive exercise increased muscle lactate, and decreased phosphocreatine and ATP with no effect of acclimation. Interestingly, hypoxia-acclimated fish had higher pHe and pHi than control in all exercise time points. Red muscle ATP was lower in hypoxia-acclimated fish versus control at each sample period. Moreover, acclimated fish increased lactate dehydrogenase activity in the red muscle. Hypoxia acclimation increased white muscle ATP and hexokinase activity, a glycolytic enzyme. In a gait-transition swim test, hypoxia-acclimated fish recruited anaerobic-powered burst swimming at lower speeds in normoxia compared to control fish. These data suggest that acclimation increases reliance on anaerobic metabolism, and does not benefit recovery from exhaustive exercise.

Intracerebroventricular administration of the exercise hormone irisin or acute strenuous exercise alleviates epileptic seizure-induced neuroinflammation and improves memory dysfunction in rats

BackgroundStatus epilepticus is a common and potentially life-threatening neurological emergency with a high risk for cognitive and neurobiological impairment. Our aim was to evaluate the neuroprotective effects of centrally administered irisin and acute exhausting exercise against oxidative brain injury and memory dysfunction due to a pentylenetetrazole (PTZ)-induced single seizure. Male Sprague Dawley rats with intracerebroventricular (icv) cannulas were randomly divided into intraperitoneally (ip) saline-injected control and PTZ-injected (45 mg/kg) seizure groups. Both the control and PTZ groups were then treated with irisin (7.5 µg/kg, 2 µl, icv), saline (2 µl, icv) or were forced to an acute bout of strenuous exercise before the ip injection of saline (control) or PTZ. Seizures were evaluated using the Racine score. To evaluate memory performance, a passive avoidance test was performed before and after PTZ injection. Following euthanasia at the 24th hour of seizure induction, brain tissues were removed for histopathological examination and for evaluating oxidative damage, antioxidant capacity, and neurotransmitter levels.ResultsGlutamate/GABA imbalance observed in PTZ rats was corrected by irisin administration (p < 0.001/p < 0.01), while irisin prevented the generation of reactive oxygen species and lipid peroxidation (p < 0.05 − 0.001) and replenished the antioxidant catalase and glutathione levels (p < 0.01–0.01) in the cerebral tissue, and reduced the histologically evident neuronal injury due to a single seizure (p < 0.05 − 0.01). Irisin also delayed the onset of seizures (p < 0.05) and improved memory dysfunction (p < 0.05), but did not affect the severity of seizures. The acute exhaustive swimming exercise completed before PTZ-seizure depressed glutamate level (p < 0.001), maintained the oxidant/antioxidant balance, alleviated neuronal injury (p < 0.05 − 0.01) and upregulated cerebral BDNF expression (p < 0.05).ConclusionIn conclusion, acute high-intensity exercise or exogenously administered irisin provides neuroprotection by maintaining the balance of excitatory/inhibitory neurotransmitters and oxidant/antioxidant systems.

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.

Geniposide alleviates heart failure with preserved ejection fraction in mice by regulating cardiac oxidative stress via MMP2/SIRT1/GSK3β pathway.

Heart failure with preserved ejection fraction (HFpEF) is a complex clinical syndrome with cardiac dysfunction, fluid retention and reduced exercise tolerance as the main manifestations. Current treatment of HFpEF is using combined medications of related comorbidities, there is an urgent need for a modest drug to treat HFpEF. Geniposide (GE), an iridoid glycoside extracted from Gardenia Jasminoides, has shown significant efficacy in the treatment of cardiovascular, digestive and central nervous system disorders. In this study we investigated the therapeutic effects of GE on HFpEF experimental models in vivo and in vitro. HFpEF was induced in mice by feeding with HFD and L-NAME (0.5 g/L) in drinking water for 8 weeks, meanwhile the mice were treated with GE (25, 50 mg/kg) every other day. Cardiac echocardiography and exhaustive exercise were performed, blood pressure was measured at the end of treatment, and heart tissue specimens were collected after the mice were euthanized. We showed that GE administration significantly ameliorated cardiac oxidative stress, inflammation, apoptosis, fibrosis and metabolic disturbances in the hearts of HFpEF mice. We demonstrated that GE promoted the transcriptional activation of Nrf2 by targeting MMP2 to affect upstream SIRT1 and downstream GSK3β, which in turn alleviated the oxidative stress in the hearts of HFpEF mice. In H9c2 cells and HL-1 cells, we showed that treatment with GE (1 μM) significantly alleviated H2O2-induced oxidative stress through the MMP2/SIRT1/GSK3β pathway. In summary, GE regulates cardiac oxidative stress via MMP2/SIRT1/GSK3β pathway and reduces cardiac inflammation, apoptosis, fibrosis and metabolic disorders as well as cardiac dysfunction in HFpEF. GE exerts anti-oxidative stress properties by binding to MMP2, inhibiting ROS generation in HFpEF through the SIRT1/Nrf2 signaling pathway. In addition, GE can also affect the inhibition of the downstream MMP2 target GSK3β, thereby suppressing the inflammatory and apoptotic responses in HFpEF. Taken together, GE alleviates oxidative stress/apoptosis/fibrosis and metabolic disorders as well as HFpEF through the MMP2/SIRT1/GSK3β signaling pathway.

The Contrasting Effects of Two Distinct Exercise Training Modalities on Exhaustive Exercise-Induced Muscle Damage in Mice May Be Associated with Alterations in the Gut Microbiota.

Exhaustive exercise is known to induce muscle damage characterized by inflammation and oxidative stress. Although "regular" and "weekend warrior" exercise regimens have been shown to confer comparable health benefits in human studies, such as reduced risks of all-cause, cardiovascular disease (CVD), and cancer mortality, their differential impacts on muscle damage post-exhaustive exercise remain unclear. This study aimed to compare the effects of long-term, moderate-intensity (LTMI) and short-term, high-intensity (STHI) training modalities, matched for total exercise volume, on gut microbiota, short-chain fatty acids (SCFAs), and exhaustive exercise-induced muscle damage in mice, as well as to evaluate the correlation between these factors. LTMI is considered a regular exercise regimen, while STHI shares some similarities with the "weekend warrior" pattern, such as promoting exercise intensity and condensing training sessions into a short period. Our findings indicate that LTMI training significantly enhanced the abundance of SCFA-producing bacteria, including Akkermansia, Prevotellaceae_NK3B31_group, Odoribacter, Alistipes, and Lactobacillus, thereby increasing SCFA levels and attenuating muscle damage following exhaustive swimming. In contrast, STHI training increased the abundance of opportunistic pathogens such as Staphylococcus and Bilophila, without altering SCFA levels, and was associated with exacerbated muscle damage. Moreover, we observed a significant negative correlation between the abundance of SCFA-producing bacteria and SCFA levels with the expression of inflammatory cytokines in the muscle of mice post-exhaustive exercise. Conversely, the abundance of Staphylococcus and Bilophila showed a notable positive correlation with these cytokines. Additionally, the effects of LTMI and STHI on exhaustive exercise-induced muscle damage were transmissible to untrained mice via fecal microbiota transplantation, suggesting that gut microbiota changes induced by these training modalities may contribute to their contrasting impacts on muscle damage. These results underscore the significance of selecting an appropriate training modality prior to engaging in exhaustive exercise, with implications for athletic training and injury prevention.

Machine learning prediction of pulmonary oxygen uptake from muscle oxygen in cycling

ABSTRACT The purpose of this study was to test whether a machine learning model can accurately predict VO2 across different exercise intensities by combining muscle oxygen (MO2) with heart rate (HR). Twenty young highly trained athletes performed the following tests: a ramp incremental exercise, three submaximal constant intensity exercises, and three severe intensity exhaustive exercises. A Machine Learning model was trained to predict VO2, with model inputs including heart rate, MO2 in the left (LM) and right legs (RM). All models demonstrated equivalent results, with the accuracy of predicting VO2 at different exercise intensities varying among different models. The LM+RM+HR model performed the best across all intensities, with low bias in predicted VO2 for all intensity exercises (0.08 ml/kg/min, 95% limits of agreement: −5.64 to 5.81), and a very strong correlation (r = 0.94, p < 0.001) with measured VO2. Furthermore, the accuracy of predicting VO2 using LM+HR or RM+HR was higher than using LM+RM, and higher than the accuracy of predicting VO2 using LM, RM, or HR alone. This study demonstrates the potential of a machine learning model combining MO2 and HR to predict VO2 with minimal bias, achieving accurate predictions of VO2 for different intensity levels of exercise.

T-Allele Carriers of Mono Carboxylate Transporter One Gene Polymorphism rs1049434 Demonstrate Altered Substrate Metabolization during Exhaustive Exercise.

Polymorphism rs1049434 characterizes the nonsynonymous exchange of adenosine (A) by thymidine (T) in the gene for monocarboxylate transporter 1 (MCT1). We tested whether T-allele carriers of rs1049434 demonstrate increased accumulation of markers of metabolic strain. Physically active, healthy, young male subjects (n = 22) conducted a power-matched one-legged cycling exercise to exhaustion. Metabolic substrates in capillary blood, selected metabolic compounds, and indices for the slow oxidative phenotype of vastus lateralis muscle were quantified in samples collected before and after exercise. The genotypes of the rs1049434 polymorphism were determined with polymerase chain reactions. One-legged exercise affected the concentration of muscle metabolites entering the tricarboxylic acid cycle, such as acetyl-co-enzyme A (+448%) and acetyl-L-carnitine (+548%), muscle glycogen (-59%), and adenosine monophosphate (-39%), 30 min post-exercise. Exercise-related variability in the muscular concentration of glycogen, long-chain acyl co-enzyme As and a triglyceride, nicotinamide adenine dinucleotide (NADH), and adenosine monophosphate (AMP) interacted with rs1049434. T-allele carriers demonstrated a 39% lesser reduction in glycogen after exercise than non-carriers when NADH increased only in the non-carriers. Muscle lactate concentration was 150% higher, blood triacyl-glyceride concentration was 53% lower, and slow fiber percentage was 20% lower in T-allele carriers. The observations suggest a higher anaerobic glycolytic strain during exhaustive exercise and a lowered lipid handling in T-allele non-carriers.

Long-term Changes in Body Composition and Exercise Capacity Following Calorie Restriction and Exercise Training in Older Patients with Obesity and Heart Failure With Preserved Ejection Fraction

Obesity combined with heart failure with preserved ejection fraction (HFpEF) is the dominant form of HF among older persons. In a randomized trial, we previously showed that a 5-month calorie restriction (CR) program, with or without aerobic exercise training (AT), resulted in significant weight and fat loss and improved exercise capacity. However, little is known regarding the long-term effects of these outcomes after a short-term (5-month) intervention of CR with or without AT in older patients with obesity and HFpEF. Sixteen participants from either the CR or CR+AT who experienced significant weight loss ≥ 2 kg were reexamined after a long-term follow-up endpoint (28.0 ± 10.8 months) without intervention. The follow-up assessment included body weight and composition via dual-energy X-ray absorptiometry and exhaustive cardiopulmonary treadmill exercise testing. Compared to the 5-month time-point intervention endpoint, at the long-term follow-up endpoint, mean body weight increased +5.2 ± 4.0 kg (90.7 ± 11.2 kg vs 95.9 ± 11.9; P < 0.001) due to increased fat mass (38.9 ± 9.3 vs 43.8 ± 9.8; P < 0.001) with no change in lean mass (49.6 ± 7.1 vs 49.9±7.6; P = 0.67), resulting in worse body composition (decreased lean-to-fat mass). Change in total mass was strongly and significantly correlated with change in fat mass (r = 0.75; P < 0.001), whereas there appeared to be a weaker correlation with change in lean mass (r = 0.50; P = 0.051). Additionally, from the end of the 5-month time-point intervention endpoint to the long-term follow-up endpoint, there were large, significant decreases in VO2peak (-2.2 ± 2.1 mL/kg/min; P = 0.003) and exercise time (-2.4 ± 2.6 min; P = 0.006). There appeared to be an inverse correlation between the change in VO2peak and the change in fat mass (r = -0.52; P = 0.062). Although CR and CR+AT in older patients with obesity and HFpEF can improve body composition and exercise capacity significantly, these positive changes diminish considerably during long-term follow-up endpoints, and regained weight is predominantly adipose, resulting in worsened overall body composition compared to baseline. This suggests a need for long-term adherence strategies to prevent weight regain and maintain improvements in body composition and exercise capacity following CR in older patients with obesity and HFpEF.