Differences In Exercise Tolerance Research Articles

Sex differences in the intensity–duration relationships of the severe- and extreme-intensity exercise domains

ABSTRACT Extreme-intensity exercise is described by W′ext (analogous to J′ for isometric exercise) that is smaller than W′ of severe-intensity exercise (W′sev) in males. Sex differences in exercise tolerance appear to diminish at near-maximal exercise, however, there is evidence of greater contributions of peripheral fatigue (i.e. potentiated twitch force; Qpot) in males during extreme-intensity exercise. Therefore, the current study tested the hypotheses that J′ext would not be different between males and females, however, males would exhibit a greater reduction in neuromuscular function (i.e. maximal voluntary contraction, MVC; Qpot) following extreme-intensity exercise. Seven males and 7 females completed three severe- (Tlim: 2–4 min, S3; 5–8 min, S2; 9–15 min, S1) and three extreme-intensity (70, 80, 90%MVC) knee-extension bouts. MVC and Qpot relative to baseline were compared at task failure and at 150 s of recovery. J′ext was significantly less than J′sev in males (2.4 ± 1.2kJ vs 3.9 ± 1.3kJ; p = 0.03) and females (1.6 ± 0.8kJ vs 2.9 ± 1.7kJ; p = 0.05); however, there were no sex differences in J′ext or J′sev. MVC (%Baseline) was greater at task failure following extreme-intensity exercise (76.5 ± 20.0% vs 51.5 ± 11.5% in males, 75.7 ± 19.4% vs 66.7 ± 17.4% in females), but was not different at 150 s of recovery (95.7 ± 11.8% in males, 91.1 ± 14.2% in females). Reduction in Qpot, however, was greater in males (51.9 ± 16.3% vs 60.6 ± 15.5%) and was significantly correlated with J′ext (r 2 = 0.90, p < 0.001). Although there were no differences in the magnitude of J′ext, differences in MVC and Qpot are evidence of sex-specific responses and highlight the importance of appropriately characterizing exercise intensity regarding exercise domains when comparing physiological responses in males and females. Highlights We have previously shown evidence that extreme-intensity dynamic exercise is described by W′ext in males and smaller than W′sev. We currently tested for potential sex differences in J′ext (isometric analogue to W′) and neuromuscular responses (i.e. maximal voluntary contraction, MVC; potentiated twitch force, Qpot) during extreme-intensity exercise. J′ext and extreme-intensity exercise tolerance was not different between males and females. The reduction in MVC was not different across extreme-intensity exercise across males and females, whereas the reduction in Qpot was greater in males following all extreme-intensity exercises, although not after exercise at 90%MVC. Together, although extreme-intensity exercise tolerance is not different, these data highlight differences in the contributing mechanisms of fatigue during severe- and extreme-intensity exercise between males and females.

Variability in exercise tolerance and physiological responses to exercise prescribed relative to physiological thresholds and to maximum oxygen uptake.

What is the central question of this study? Does prescribing exercise intensity using physiological thresholds create a more homogeneous exercise stimulusthanusing traditional intensity anchors? What is the main finding and its importance? Prescribing exercise using physiological thresholds, notably critical power, reduced the variability in exercise tolerance and acute metabolic responses. At higher intensities, approaching or exceeding the transition from heavy to severe intensity exercise, the imprecision of using fixed % as an intensity anchor becomes amplified. The objective of this study was to determine whether the variability in exercise tolerance and physiological responses is lower when exercise is prescribed relative to physiological thresholds (THR) compared to traditional intensity anchors (TRAD). Ten individuals completed a series of maximal exercise tests and a series of moderate (MOD), heavy (HVY) and severe intensity (HIIT) exercise bouts prescribed using THR intensity anchors (critical power and gas exchange threshold) and TRAD intensity anchors (maximum oxygen uptake; ). There were no differences in exercise tolerance or acute response variability between MODTHR and MODTRAD . All individuals completed HVYTHR but only 30% completed HVYTRAD . Compared to HVYTHR , where work rates were all below critical power, work rates in HVYTRAD exceeded critical power in 70% of individuals. There was, however, no difference in acute response variability between HVYTHR and HVYTRAD . All individuals completed HIITTHR but only 20% completed HIITTRAD . The variability in peak (F=0.274) and average (F=0.318) blood lactate responses was lower in HIITTHR compared to HIITTRAD . The variability in W' depletion (the finite work capacity above critical power) after the final interval bout was lower in HIITTHR compared to HIITTRAD (F=0.305). Using physiological thresholds to prescribe exercise intensity reduced the heterogeneity in exercise tolerance and physiological responses to exercise spanning the boundary between the heavy and severe intensity domains. To increase the precision of exercise intensity prescription, it is recommended that, where possible, physiological thresholds are used in place of .

Hypoxic training in rehabilitation of patients at the early stages of recovery after SARS-CoV-2 pneumonia

To evaluate efficacy and safety of hypoxic-hyperoxic therapy in rehabilitation after SARS-CoV-2 pneumonia. There were 44 patients aged 49-75 years in early recovery period after previous SARS-CoV-2 pneumonia (ICD-10 U07.1 and U07.2). Patients were divided into 2 groups depending on treatment strategy: group 1 (n=23) - rehabilitation treatment with therapeutic exercises, massage and physiotherapy; group 2 (n=21) - basic procedures with hypoxic-hyperoxic therapy. At initial evaluation, we found positive tendencies of rehabilitation in both groups. There were no side effects associated with hypoxic-hyperoxic therapy in the second group. Patients positively perceived this method of rehabilitation. There were significant between-group differences in exercise tolerance (p<0.05). These data indicate more favorable physical recovery in the second group and similar improvement of psycho-emotional status in both groups. Hypoxic-hyperoxic therapy is effective and safe approach in rehabilitation of patients with previous SARS-CoV-2 pneumonia. It is necessary to continue searching for effective methods of rehabilitation and develop accurate rehabilitation methods for various groups of patients.

The impact of beetroot juice intake on muscle oxygenation and performance during rhythmic handgrip exercise

BackgroundDespite studies investigating the effect of beetroot juice (BJ) ingestion on exercise performance in several modes of exercise, it is important to evaluate how untrained subjects respond to BJ intake during fatiguing resistance exercise. Therefore, the present study investigated the effect of BJ consumption on muscle oxygenation parameters during rhythmic handgrip exercise and exercise recovery in untrained subjects. Furthermore, exercise tolerance was also evaluated. MethodsIn a randomized, double-blind, crossover fashion, thirteen healthy young subjects ingested a single dose of BJ or placebo (PLA). At 150 minutes after BJ or PLA intake, participants performed 1 bout of rhythmic handgrip exercise until fatigue and muscle oxygenation parameters were continuously monitored during exercise and exercise recovery. ResultsDuring exercise, no significant difference in deoxygenated hemoglobin and total hemoglobin were observed after supplementation. However, a significantly faster muscle oxygen saturation during exercise recovery was observed after BJ ingestion as compared to PLA without significant changes in total hemoglobin. No significant difference in exercise tolerance after supplementation was observed. Conclusiona single dose of BJ improves muscle reoxygenation during the recovery period of rhythmic handgrip exercise in untrained subjects, despite no changes in oxygen extraction, blood volume, and exercise tolerance.

Gender-related dynamics of exercise tolerance in patients with acute coronary syndrome undergoing the outpatient phase of rehabilitation

Background. The relevance of the comparative study of exercise tolerance in male and female cardiac patients is due to the need to individualize physical rehabilitation programs.&#x0D; Aims: to study the impact of gender on exercise tolerance in patients with acute coronary syndrome undergoing a course of rehabilitation in a day hospital.&#x0D; Methods. 110 patients with acute coronary syndrome were examined: 81 men (73.6%) aged 34 to 75 years and 29 women (26.4%) aged 44 to 74 years. In accordance with the purpose of the study, all patients were exposed to stress testing before and after the end of the three-week rehabilitation course.&#x0D; Results. According to the analysis of the six-minute walk test and the Bicycle ergometric test, men had better physical endurance than women. Features of hemodynamic indicators during physical activity also correlate with gender: in comparison with men, the maximum physical load in women was accompanied by higher heart rate values. At the end of the rehabilitation course, women had a more pronounced improvement of Bicycle ergometry indicators: a greater increase in maximum power and the percentage of load performed during the test.&#x0D; Conclusions. The gender differences in exercise tolerance in cardiac patients identified in the study should be taken into account when designing rehabilitation programs.

Lifelong pulmonary sequelae of bronchopulmonary dysplasia.

To summarize the current literature evaluating long-term pulmonary morbidity among surviving very preterm infants with bronchopulmonary dysplasia (BPD). BPD predisposes very preterm infants to adverse respiratory signs and symptoms, greater respiratory medication use, and more frequent need for rehospitalization throughout early childhood. Reassuringly, studies also indicate that older children and adolescents with BPD experience, on average, similar functional status and quality of life when compared to former very preterm infants without BPD. However, measured deficits in pulmonary function may persist in those with BPD and indicate an increased susceptibility to early-onset chronic obstructive pulmonary disease during adulthood. Moreover, subtle differences in exercise tolerance and activity may put survivors with BPD at further risk of future morbidity in later life. Despite advances in neonatal respiratory care, a diagnosis of BPD continues to be associated with significant pulmonary morbidity over the first two decades of life. Long-term longitudinal studies are needed to determine if recent survivors of BPD will also be at increased risk of debilitating pulmonary disease in adulthood.

Exercise Physiology Across the Lifespan in Cystic Fibrosis.

Cystic fibrosis (CF), a severe life-limiting disease, is associated with multi-organ pathologies that contribute to a reduced exercise capacity. At present, the impact of, and interaction between, disease progression and other age-related physiological changes in CF on exercise capacity from child- to adult-hood is poorly understood. Indeed, the influences of disease progression and aging are inherently linked, leading to increasingly complex interactions. Thus, when interpreting age-related differences in exercise tolerance and devising exercise-based therapies for those with CF, it is critical to consider age-specific factors. Specifically, changes in lung function, chronic airway colonization by increasingly pathogenic and drug-resistant bacteria, the frequency and severity of pulmonary exacerbations, endocrine comorbidities, nutrition-related factors, and CFTR (cystic fibrosis transmembrane conductance regulator protein) modulator therapy, duration, and age of onset are important to consider. Accounting for how these factors ultimately influence the ability to exercise is central to understanding exercise impairments in individuals with CF, especially as the expected lifespan with CF continues to increase with advancements in therapies. Further studies are required that account for these factors and the changing landscape of CF in order to better understand how the evolution of CF disease impacts exercise (in)tolerance across the lifespan and thereby identify appropriate intervention targets and strategies.

3311A new rat model of chronic thromboembolic pulmonary hypertension induced by repeated intravenous administration of biodegradable alginate microspheres

Abstract Introduction Chronic thromboembolic pulmonary hypertension (CTEPH) is life-threatening complication of pulmonary embolism (PE) with insufficiently understood mechanisms. Several rodent CTEPH models based on i.v. administration of non-biodegradable microparticles have been validated for preclinical studies. Major limitation of these models is the lack of partial dissolution of emboli following their entrapment in the lung vasculature. Purpose The study was aimed at development and validation of rat CTEPH model based on recurrent embolization of (sub)segmental pulmonary artery branches with biodegradable microspheres. Methods Male Wistar rats were used for the experiments. Pulmonary vasculature was embolized either with sodium alginate microspheres (MS) or with autologous blood clots (AT). The animals were randomized into the following groups: i) controls: saline at a volume of 50 μL was injected 4 times with 8-day interval into the tail vein; the same regimen was used in two next groups; ii) AT; iii) MS4; iv) MS8: MS were administered 8 times with 4-day interval. Histological examination of the lungs was performed after 2 and 6 weeks after the last injection. 6 weeks after the last injection the following analyses were performed: treadmill test, transthoracic echocardiography (TTE), right ventricular catheterization with measurement of right ventricular systolic pressure (RVSP), determination of serum endothelin-1 level. Results The survival rate in the MS8 group was 50%. In the other groups, there were no animal deaths. Multiple emboli were found in the lumen of (sub)segmental pulmonary artery branches 2 weeks after the last injection in MS4 and MS8 groups. Increased diameter and thickening of the bronchial arterial wall were also registered. After 6 weeks, the index of hypertrophy of vessel wall in MS4 and MS8 groups was significantly higher than in controls (p=0.041 and p=0.006, respectively) (Fig. 1). No sign of vascular remodeling was identified in the branches of the pulmonary artery in the AT group. Exercise tolerance was significantly reduced in both MS4 and MS8 groups compared with the controls (p=0.025 and p=0.008, respectively). There were no significant differences in exercise tolerance between the AT and control groups. TTE data indicate a significant increase in the diameter of the pulmonary trunk and the right ventricular outflow tract in the MS8 group compared with controls and AT (p&lt;0.05). Significant increase in RVSP as well as in endothelin-1 level versus controls was found only in the MS8 group. Figure 1. Histological changes in the branches of the pulmonary artery 6 weeks after the last injection of emboli. Conclusion Recurrent (×8) intravenous administration of MS in rats resulted in CTEPH development characterized by specific lung vasculature remodelling, reduced exercise tolerance, and persistent rise in RVSP. The model developed can be used for preclinical testing of promising drug candidates.

P2686Endothelial reaction mediates enhanced external counterpulsation effects in post-MI cardiac rehabilitation

Abstract Introduction The mechanisms mediating benefits of enhanced external counterpulsation (EECP) are disputable since the origin of the method. One of the possible explanations presumes increased diastolic flow leads to changes of endothelial function and plays a crucial role in alleviating the symptoms of angina and heart failure; the exact mechanisms of action are still under investigation, though the endothelial hypothesis possesses strong evidence. Purpose To reveal the impact of repeated EECP on endothelial function of patients undergoing cardiac rehabilitation program after myocardial infarction (MI) and to identify possible clinical implications of these changes. Methods The randomized sham-controlled study included 46 patients with coronary artery disease who suffered from ST-elevation MI (STEMI) 4–8 weeks prior to enrollment in 2017–2018. All patients had undergone primary PCI due to STEMI in 2–24 hours after the event. Echo parameters, exercise tolerance and the levels of ADMA and nitric oxide (NO) metabolites (total content, nitrite and nitrate) in plasma were determined at the enrollment stage and at three month follow-up. Patients were randomized and given 35 h of active counterpulsation (main group, n=24) or inactive counterpulsation (control group, n=22) over a six-week period after enrollment. Results The analysis showed no significant difference between groups at baseline: mean ejection fraction was 46% in the main group and 45% in the control group, no difference in exercise tolerance. The mean characteristics of endothelial function at baseline were similar in both main and control groups: total NO metabolites (17.3±2.14 μmol/L vs. 19.6±3.31, p=0. 42), nitrite level (0.76±0.17 μmol/L vs. 0.75±0.21, p=0. 36), ADMA level (0.78±0.15 μmol/L vs. 0.81±0.20, p=0. 22). At three month follow up 41,7% of patients of the main group showed improvement of one class of NYHA classification compared to 22,7% in the control group (U=122.3, p=0.012), agreed with improved exercise tolerance: average +2.8 MET in main group in opposite to only +0.8 MET in the controls (U=104, p=0.007). Control group demonstrated no significant dynamics of NO metabolites concentration comparing to baseline values, while in the main group there was a significant decrease of ADMA – 0.57±0.11 μmol/L (Z=r=−2.46, p=0.013) and increase of nitrite level – 1,12±0. 18 μmol/L (Z=r=−2.57, p=0.011), with no changes in total NO metabolites content. The further analysis demonstrated strong correlation between exercise capacity gain and ADMA decrease (R=r=−0.52, p=0.008) or nitrite elevation (R=0.48, p=0.012), with ADMA/nitrite ratio being the strongest predictor of clinical improvement (R=0.68, p=0.002). Conclusion Active EECP improves exercise capacity and heart failre symptoms in patients undergoing post-MI rehabilitation, with those effects being associated with endothelial function enhancement.

Impact of dietary nitrate supplementation on the speed/duration relationship in mice with sickle cell anemia

Sickle cell disease (SCD) compromises nitric oxide (NO) bioavailability and results in a plethora of cardiopulmonary and skeletal muscle complications causing severe exercise intolerance. It is now widely recognized that dietary nitrate can be reduced to nitrite and, subsequently, NO and impact hemodynamic and metabolic control during exercise. Therefore, the purpose of this investigation was to measure the impact of nitrate supplementation on exercise capacity as measured by the running speed/ exercise duration relationship (critical speed, CS) and the anaerobic work capacity (W′, the finite work capacity available above CS) in mice with SCD. We tested the hypothesis that dietary nitrate supplementation via beetroot juice (BR) would attenuate the exercise intolerance observed in mice with SCD. Ten wild‐type (WT) and 18 Berkley sickle‐cell mice (BERK) received either water (WT: n=10, BERK: n=10) or nitrate‐rich BR (BERK+BR: n=8, nitrate dose 1 mmol/kg/day) for five days). Following the supplementation period, all mice performed 4 constant‐speed treadmill tests that resulted in fatigue within 1.5 to 20 min. Time to fatigue vs. treadmill speed were fit to a hyperbolic model to determine CS. Speed and time to exhaustion for WT, BERK, and BERK+BR conformed to a hyperbolic relationship (WT: r2 = 0.93 ± 0.02, BERK: r2 = 0.97 ± 0.01, BERK+BR: r2= 0.97 ± 0.03, p&gt;0.05). CS was significantly lower in BERK when compared to WT and BERK+BR with no significant difference between WT and BERK+BR (WT: 33.1 ± 1.5, BERK: 24.7 ± 0.7, BERK+BR: 31.9 ± 1.4 m/min, p&lt;0.05). Additionally, the W′ was significantly higher in BERK relative to WT and BERK+BR (WT: 1456.2 ± 237.2, BERK: 2639.2 ± 106.8, BERK+BR: 1134.7 ± 156.7, P&lt;0.05). To summarize, exercise tolerance, as measured via CS, was significantly lower in BERK mice relative to WT. However, BERK mice that had received a 5‐day dietary nitrate intervention exhibited no difference in exercise tolerance when compared to WT. In addition, the W′ was significantly higher in BERK mice relative to WT, but this difference was not observed in BERK+BR. The CS threshold is a well‐described fundamental feature of exercise energetics that represents the highest sustainable rate of aerobic metabolism and remains valid across species. Considering the lower CS in BERK mice and the ability of BR to restore CS in BERK mice, these results provide compelling support for the use of a dietary nitrate intervention to improve functionality in the SCD patient population.Support or Funding InformationFunded by NIH (R01HL125642) to DCI and Colorado Nutrition and Obesity Research Center (P30DK048520) award to SKF.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

L’outil DISC améliore la communication et les résultats de la réhabilitation respiratoire : une approche comportementale adaptée

Competence in personal relationships is essential for a caregiver, especially in pulmonary rehabilitation (PR). Considering the behavioral profile of patients might help to optimize their management and the results of PR. We evaluated eight hundred and thirty-two consecutive patients with chronic respiratory disease who received eight weeks of home-based PR. Their exercise tolerance (six-minute stepper test, 6MST), mood (HAD), and quality of life (VSRQ, MRF28) were evaluated at the beginning and end of PR. For six hundred and ninety patients, a behavioral approach was implemented at the beginning of PR by using the DISC tool to identify four behavioral profiles: dominance, influence, steadiness, conscientiousness. The remaining 142 patients served as the control group. Subjectively, the therapeutic alliance was more easily established with the behavioral approach. Compared with the control group, patients with the "steadiness" profile were younger (60.7±12 years) and mostly female (52.8%), whereas patients with the "conscientiousness" profile were older (67.5±10.6 years) and mostly male (85.5%). The four behaviorally profiled groups showed no differences in exercise tolerance, mood, or quality of life scores at baseline. Globally, all patients improved their exercise tolerance, mood and quality of life. The percentage of responders to 6MST and VSRQ (>MCID) was 7.5% and 5.3% higher with the behavioral approach. For non-responders to 6MST and VSRQ (<MCID), only patients benefiting from the behavioral approach improved the other parameters studied, patients from control group having exhibited no improvement at all. The DISC-guided behavioral approach improves the patient-caregiver relationship and achieves better results at the end of PR.

Poster 124: Difference in Exercise Tolerance During In-Clinic Concussion Recovery Workouts Among Patients with History of Self-Reported Headache, Learning Disability, Attention Deficit-Hyperactivity Disorder, or Mood Disorder

PM&RVolume 10, Issue 9S1 p. S45-S45 Poster 124: Difference in Exercise Tolerance During In-Clinic Concussion Recovery Workouts Among Patients with History of Self-Reported Headache, Learning Disability, Attention Deficit-Hyperactivity Disorder, or Mood Disorder Marie Van Tubbergen PhD, Marie Van Tubbergen PhD Ann Arbor, MI, United StatesSearch for more papers by this authorAbigail R. Johnson PhD, Abigail R. Johnson PhDSearch for more papers by this authorAndrew Sas MD, PhD, Andrew Sas MD, PhDSearch for more papers by this authorMichael Popovich MD, Michael Popovich MDSearch for more papers by this authorJames T. Eckner MD, MS, James T. Eckner MD, MSSearch for more papers by this author Marie Van Tubbergen PhD, Marie Van Tubbergen PhD Ann Arbor, MI, United StatesSearch for more papers by this authorAbigail R. Johnson PhD, Abigail R. Johnson PhDSearch for more papers by this authorAndrew Sas MD, PhD, Andrew Sas MD, PhDSearch for more papers by this authorMichael Popovich MD, Michael Popovich MDSearch for more papers by this authorJames T. Eckner MD, MS, James T. Eckner MD, MSSearch for more papers by this author First published: 26 September 2018 https://doi.org/10.1016/j.pmrj.2018.08.143Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat No abstract is available for this article. Volume10, Issue9S12018 AAPM&R Annual Assembly AbstractsSeptember 2018Pages S45-S45 RelatedInformation

Impact of chronic free hemoglobin infusion on skeletal muscle microvascular PO2 dynamics in rats

Patients with hemolytic diseases (i.e. sickle cell anemia) exhibit severely compromised exercise capacity and quality of life. This is likely due, at least in part, to chronic exposure to free hemoglobin (Hb) which results in a robust reduction in nitric oxide (NO) bioavailability and, particularly when combined with systemic hypoxia, enacts a proinflammatory cascade that causes vascular dysfunction and remodeling within the pulmonary circulation. Similar downstream effects may occur which could disrupt the QO2/VO2 relationship within skeletal muscle and thus impair tolerance to exercise. Therefore, the purpose of this investigation was to test the hypothesis that chronic exposure to free Hb would lower the microvascular PO2 (PO2mv, the pressure head that facilitates blood‐myocyte O2 flux) at rest and during muscle contractions with a greater deficit observed in rats exposed to hypoxia+Hb. Using programmable micropump technology, 8 young‐adult male Sprague‐Dawley rats were housed in normoxia (Hb+Nx, n=4) or hypoxia (Hb+Hx, n=4) while exposed to 60 mg/day Hb for 18 days while 4 rats were outfitted with dummy infusion pumps (SHAM, n=4) and were housed in normoxia. Following infusion, all rats performed a graded treadmill exercise test to fatigue for the determination of endurance capacity. PO2mv was then measured during 180s of electrically induced (1‐Hz) twitch spinotrapezius muscle contractions. There were no between group differences in exercise tolerance (average run time 16–18 min, p&gt;0.05). While there were no significant differences in any PO2mv kinetic parameter, exposure to hypoxia and Hb resulted in a significantly greater resting baseline (SHAM: 28.3 ± 4, Hb+Nx: 31.5 ± 2, Hb+Hx: 42.8 ± 3 mmHg) and contracting steady‐state PO2 (SHAM: 20.70 ± 4, Hb+Nx: 26 ± 2, Hb:Hx: 36.3 ± 2 mmHg) when compared to SHAM and Hb+Nx conditions, while the contracting steady‐state PO2 was also significantly higher in Hb+Nx vs. SHAM (p&lt;0.05). Blood hematocrit was significantly higher in Hb+Hx when compared to SHAM and Hb+Nx with no significant differences between SHAM and Hb+Nx (SHAM: 48.5 ± 3, Hb+Nx: 43.1 ± 3, Hb+Hx: 54.7 ± 2%, p&lt;0.05). Contrary to our original hypothesis, combined exposure to free Hb and hypoxia resulted in a greater baseline and contracting steady‐state PO2mv while Hb alone raised the steady‐state PO2mv relative to SHAM operated rats. Given that free Hb results in oxidative stress and cellular damage, the elevated PO2mv in both Hb groups likely reflects an impaired ability to utilize oxygen (↓VO2) within the skeletal muscle. This is supported by the lack of differences in exercise tolerance in Hb vs. SHAM despite an increased Hct (i.e. oxygen carrying capacity) observed in the Hb+Hx rats and significantly greater steady‐state PO2mv in both Hb groups. These results carry robust implications for those suffering from hemolytic diseases and provides a potential mechanism by which chronic exposure to free Hb impacts exercise tolerance and quality of life.Support or Funding InformationFunded by NIH (R01HL125642) to DCI and Colorado Nutrition and Obesity Research Center (P30DK048520) award to SKF.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Analysis of cardiopulmonary exercise testing results of 46 adolescent idiopathic scoliosis patients without pulmonary dysfunction

Objective To explore the cardiopulmonary function and exercise capacity of adolescent idiopathic scoliosis (AIS) patients without pulmonary dysfunction. Methods In this retrospective study, the results of exercise tests administered to AIS patients without pulmonary dysfunction were reviewed seeking any consistent relationship between scoliosis location and severity and the test results. Correlations relating pulmonary function, body mass index (BMI), age and exercises tolerance were also sought. Results Forty-six patients were included, 17 with solely thoracic scoliosis, 11 with solely thoracolumbar scoliosis and 18 with both thoracic and thoracolumbar scoliosis. Ten of those studied (21.74%) had normal exercise tolerance, while in 24 exercise tolerance was mildly impaired, in 11 moderately and in 1 severely. The average peak minute ventilation (MV) of the thoracic scoliosis group [(43.11±8.47) L/min] was significantly lower than that of the thoracolumbar scoliosis group [(50.81±10.11) L/min]. The average VO2AT/kg of the thoracic+ thoracolumbar scoliosis group [(14.16±2.04) ml/kg/min] was significantly lower than that of the thoracic scoliosis group [(16.82±2.87) ml/kg/min] and of the thoracolumbar scoliosis group [(17.78±4.34) ml/kg/min]. Among the thoracic scoliosis patients, no significant difference in exercise tolerance was observed between those with moderate and severe scoliosis. The peak VO2% pred was negatively correlated with BMI, but not significantly correlated with pulmonary function or age. Conclusions Although without pulmonary dysfunction, the AIS patients showed a significantly lower tolerance for maximum exercise generally. The average peak ME was significantly lower in the thoracic scoliosis group than in the thoracolumbar scoliosis group, while the average VO2AT/kg was significantly lower in the thoracic + thoracolumbar scoliosis group than in the solely thoracic and thoracolumbar scoliosis groups. Exercise tolerance was negatively correlated with BMI, but uncorrelated with the severity of the scoliosis, pulmonary function or age. Key words: Adolescent idiopathic scoliosis; Cardiopulmonary exercise testing; Body mass index

Oral N-acetylcysteine and exercise tolerance in mild chronic obstructive pulmonary disease.

Heightened oxidative stress is implicated in the progressive impairment of skeletal muscle vascular and mitochondrial function in chronic obstructive pulmonary disease (COPD). Whether accumulation of reactive oxygen species contributes to exercise intolerance in the early stages of COPD is unknown. The purpose of the present study was to determine the effects of oral antioxidant treatment with N-acetylcysteine (NAC) on respiratory, cardiovascular, and locomotor muscle function and exercise tolerance in patients with mild COPD. Thirteen patients [forced expiratory volume in 1 s (FEV1)-to-forced vital capacity ratio < lower limit of normal (LLN) and FEV1 ≥ LLN) were enrolled in a double-blind, randomized crossover study to receive NAC (1,800 mg/day) or placebo for 4 days. Severe-intensity constant-load exercise tests were performed with noninvasive measurements of central hemodynamics (stroke volume, heart rate, and cardiac output via impedance cardiography), arterial blood pressure, pulmonary ventilation and gas exchange, quadriceps muscle oxygenation (near-infrared spectroscopy), and estimated capillary blood flow. Nine patients completed the study with no major adverse clinical effects. Although NAC elevated plasma glutathione by ~27% compared with placebo (P < 0.05), there were no differences in exercise tolerance (placebo: 325 ± 47 s, NAC: 336 ± 51 s), central hemodynamics, arterial blood pressure, pulmonary ventilation or gas exchange, locomotor muscle oxygenation, or capillary blood flow from rest to exercise between conditions (P > 0.05 for all). In conclusion, modulation of plasma redox status with oral NAC treatment was not translated into beneficial effects on central or peripheral components of the oxygen transport pathway, thereby failing to improve exercise tolerance in nonhypoxemic patients with mild COPD.NEW & NOTEWORTHY Acute antioxidant treatment with N-acetylcysteine (NAC) elevated plasma glutathione but did not modulate central or peripheral components of the O2 transport pathway, thereby failing to improve exercise tolerance in patients with mild chronic obstructive pulmonary disease (COPD).

Breathing in exercise: battle of the sexes.

Most healthy people rarely notice difficulty with their breathing either at rest or even during heavy exercise. Yet, muscular exercise makes unique and multifaceted demands on the respiratory system. During dynamic exercise, ventilation rises in proportion to the metabolic demands of the locomotor muscles. The ventilatory response to exercise requires substantial changes in intrathoracic pressure and in the work output and metabolic rate of the respiratory muscles. As a result, the oxygen cost of breathing represents a significant fraction of total oxygen uptake during intense exercise. These effects may exert significant influences on the cardiovascular response to exercise, both in total cardiac output (Harms et al. 1998) and in its distribution (Harms et al. 1997). Quantifying the metabolic demands of the respiratory muscles is necessary for understanding cardiorespiratory control during exercise. Energy expenditure required by the respiratory muscles during exercise is dependent upon exercise-induced changes in several types of mechanical work performed by the respiratory muscles. Historically, it has been very difficult to measure the oxygen or energy cost associated with exercise hyperpnoea. Aaron et al. (1992a) has estimated that in healthy untrained humans, the oxygen uptake of the respiratory muscles during maximal exercise represents ∼10% of whole-body maximum oxygen uptake. In endurance trained men, who possess a high and sustain high rates of ventilation, the oxygen uptake of the respiratory muscles can represent upwards of 15% of (Aaron et al. 1992). To date, the vast majority of studies that have made estimates of the work of breathing (WOB) during exercise have come from men. Is the WOB different for women? A compelling rationale for a sex difference exists. Women have smaller lungs and airways than height- and age-matched men (Mead, 1980), and are also likely to develop expiratory flow limitation more often than men (Guenette et al. 2007). In fact, it has been reported that women demonstrate a higher WOB than men across a range of ventilations (Guenette et al. 2007). Therefore, with an increased WOB in women, an unanswered follow-up question is: would the oxygen cost of breathing during exercise be greater in women compared to men? In this issue of The Journal of Physiology, Dominelli et al. (2015) tested this question and present their work in a detailed and well-conducted study. These researchers had nine men and nine women mimic the breathing patterns associated with five to six different exercise stages. Pressure and flow volume loops were superimposed on target loops obtained during exercise to accurately replicate the work of breathing. The authors report that for a given ventilation, women had a greater absolute oxygen cost of breathing and this represented a greater fraction of the total oxygen uptake compared to men. Additionally, in those subjects that experienced expiratory flow limitation (regardless of sex), the oxygen cost of breathing at maximal exercise was greater than in those who did not. The authors also found that neither men nor women reached their maximal effective ventilation, but women may be relatively closer to this value than men. What are the implications of these results? The greater oxygen cost of breathing in women indicates that a greater fraction of total oxygen uptake (and possibly cardiac output) is directed to the respiratory muscles, which may influence blood flow distribution during exercise. Dominelli et al. (2015) hypothesized that, when compared to men, women may show greater changes in leg blood flow when the WOB is altered by the same amount as in men. While this postulate has been theorized for many years, this study is the first to provide solid evidence to substantiate that it may indeed occur. To date, the influence of WOB on blood flow distribution during exercise has not been studied in women. To accurately determine the potential effect of sex differences on WOB-related alterations in blood flow, respiratory muscle work will need to be experimentally reduced while leg blood flow is directly measured. In summary, Dominelli et al. (2015) have provided a significant step forward in our understanding of sex differences in the work of breathing during exercise by their careful, quantitative approach in estimating the oxygen cost of breathing during exercise. The greater oxygen cost of breathing in women may have implications for the integrated physiological response to exercise. The results from this study clearly indicate that, due to morphological differences between men and women, sex differences exist in respiratory mechanics which may help account for differences in exercise tolerance between men and women. Hopefully, these finding will provide an impetus for future studies to examine the cardiovascular consequences of a sex differences in the oxygen cost of breathing.

Response to: control of muscle exercise hyperaemia: are the mechanisms found in transition?

I would like to thank Drs Poole and Behnke for their interest in our review and for initiating a scientific discussion (Poole & Behnke, 2015). If the mechanisms regulating exercise hyperaemia are to be identified in the transition from rest to exercise, it requires that the regulatory mechanisms at the onset of exercise and during ‘steady-state’ exercise conditions are the same. Our knowledge of the regulatory mechanisms during both conditions is incomplete, but it is clear that metabolic processes are too slow to account for the initial blood flow response. It therefore seems likely that the mechanism(s) initiating exercise hyperaemia are, at least in part, different from the ones that sustain it (Clifford & Hellsten, 2004). Thus, although the mechanisms governing the initial rise in exercise hyperaemia are intriguing and important, they do not necessarily provide insight into the regulatory mechanism(s) during ‘steady-state’ conditions or vice versa. It is postulated by Drs Poole and Behnke that ‘steady-state’ exercise hyperaemia for a given work rate is similar in sedentary people, elite athletes and patients and, based on this assumption, the authors make the bald statement that ‘steady-state’ blood flows may not be particularly insightful for resolving the control mechanisms. However, there is evidence demonstrating that exercise hyperaemia and heterogeneity are affected by training status (Saltin et al. 1976; Kalliokoski et al. 2001) and ageing (Proctor & Parker, 2006) as well as in disease states (Sullivan et al. 1989; Nyberg et al. 2012b). Moreover, when combined with other measurements (such as blood samples, microdialysis and/or biopsies), differences in metabolism and regulatory mechanisms can be revealed despite a similar exercise hyperaemia (Mortensen et al. 2012; Nyberg et al. 2012a). Based on the assumption that exercise hyperaemia is similar among populations, Drs Poole and Behnke suggest it is the oxygen uptake () kinetics that are insightful for explaining differences in exercise tolerance between an athlete and a heart failure patient, but neglect the importance of O2 delivery and its impact on muscle metabolism when the fatigue and thus exercise intolerance become apparent. In this light, it is critical to remark that the fatigue processes during walking/running are temporally more closely related to than the kinetics. Understanding why exercise hyperaemia and consequently O2 delivery are impaired in heart failure is key to understanding O2 utilization and exercise intolerance (Esposito et al. 2010). Our human studies have often been inspired by results obtained in advanced animal studies, and we have turned to animal models when limited in our human models. That said, there are clear anatomical and physiological differences between animals and humans that are important to cardiovascular regulation, and one should be very careful before extrapolating findings in animals to humans (see Rowell, 2007). It is my opinion that observations from animal studies should never be seen as definitive before they have been confirmed in humans. Drs Poole and Behnke indicate that the mechanisms governing exercise hyperaemia are different between populations, but the same holds true for species. Skeletal muscle perfusion rates can reach similar values in animals and humans, but the size of the heart in relation to body weight is much smaller in humans. How does this affect the kinetics and the contribution of O2-dependent and independent limitations to O2 utilization? It is clearly relevant to relate not only findings in humans to findings in animals, but also the other way around. I agree with Drs Poole and Behnke that a blend of animal and human investigations is the key to new insight into the regulatory mechanisms in health and how they are altered in disease states. I would like to reassure Drs Poole and Behnke that if we had been asked to write a more extensive review, we would certainly have included more animal work, multiple exercise conditions (for example transition, low and high intensities) and populations (for example, training status and patients). However, we were asked to write a short review on the Scandinavian perspective of blood flow regulation, and this is why our review is limited to the mechanisms regulating ‘steady-state’ exercise hyperaemia in healthy humans. None declared.

Pyruvate dehydrogenase kinase-4 contributes to the recirculation of gluconeogenic precursors during postexercise glycogen recovery

During recovery from glycogen-depleting exercise, there is a shift from carbohydrate oxidation to glycogen resynthesis. The activity of the pyruvate dehydrogenase (PDH) complex may decrease to reduce oxidation of carbohydrates in favor of increasing gluconeogenic recycling of carbohydrate-derived substrates for this process. The precise mechanism behind this has yet to be elucidated; however, research examining mRNA content has suggested that the less-abundant pyruvate dehydrogenase kinase-4 (PDK4) may reduce PDH activation during exercise recovery. To investigate this, skeletal muscle and liver of wild-type (WT) and PDK4-knockout (PDK4-KO) mice were analyzed at rest (Rest), after exercise to exhaustion (Exh), and after 2 h of recovery with ad libitum feeding (Rec). Although there were no differences in exercise tolerance between genotypes, caloric consumption was doubled by PDK4-KO mice during Rec. Because of this, PDK4-KO mice at Rec supercompensated muscle glycogen to 120% of resting stores. Therefore, an extra group of PDK4-KO mice were pair-fed (PF) with WT mice during Rec for comparison. PF mice fully replenished muscle glycogen but recovered only 50% of liver glycogen stores. Concentrations of muscle lactate and alanine were also lower in PF than in WT mice, indicating that this decrease may lead to a potential reduction of recycled gluconeogenic substrates, due to oxidation of their carbohydrate precursors in skeletal muscle, leading to observed reductions in hepatic glucose and glycogen concentrations. Because of the impairments seen in PF PDK4-KO mice, these results suggest a role for PDK4 in regulating the PDH complex in muscle and promoting gluconeogenic precursor recirculation during recovery from exhaustive exercise.

Direct comparison between pharmacological stress with adenosine triphosphate disodium and exercise stress myocardial perfusion imagings

To clarify the significance of adenosine triphosphate disodium stress myocardial perfusion imaging (ATP-MPI), we directly compared the findings of ATP-MPI with those of exercise stress myocardial perfusion imaging (Ex-MPI). ATP-MPI, Ex-MPI, and coronary angiography (CAG) were performed within 60 days in 17 coronary artery disease patients with mean age of 62.1+/-7.9 years. CAG revealed single-vessel disease (SVD) in 10 patients and multivessel disease (MVD) in seven patients. The summed stress score (SSS) of ATP-MPI was significantly higher than that of Ex-MPI (10.0 [7.8-14.3] vs. 8.0 [4-18], P<0.05). No difference in the SSS was observed between ATP-MPI and Ex-MPI in patients with SVD (8.0 [6.0-9.0] vs. 8.0 [6.0-10.0], NS), whereas this difference was significant in patients with MVD (15.0 [14.0-22.8] vs.9 [7.3-16.3], P<0.05). There was no difference in the summed rest score between ATP-MPI and Ex-MPI. The univariate logistic analysis showed that "MVD" was the significant factor influencing to the overt discrepancy between ATP-MPI and Ex-MPI (odds ratio: 9.0, 95% confidence interval: 1.07-75.84, P=0.043). The accuracy of ATP-MPI and Ex-MPI in detecting the territory of stenotic coronary vessel or previous myocardial infarction was 98.0% and 92.1% (NS), respectively. In conclusion, ATP-MPI is useful for detecting potential ischemic areas that cannot be detected by Ex-MPI, particularly in patients with MVD.

Exercise Tolerance and Thermoregulatory Responses during Cycling in Boys and Men

Physiological responses to exercise in the heat differ between prepubertal children and young adults. Whether these maturity-related variations imply lower exercise tolerance, inferior thermoregulation, and greater risk for heat injury in the child is uncertain. This study directly compared thermoregulatory and cardiovascular responses as well as endurance performance between prepubertal boys and adult males during steady-load cycling in moderately hot and cool ambient conditions with moderate humidity. Eight prepubertal boys (age 11.7 +/- 0.4 yr) and eight adult men (age 31.8 +/- 2.0 yr) performed steady-load cycling to exhaustion at an intensity equivalent to approximately 65% peak V O2 in both hot (approximately 31 degrees C) and cool (approximately 19 degrees C) environments, with fluid intake ad libitum. Exercise duration in the heat was shorter for both groups (hot: men 30.46 +/- 8.84 min, boys 29.30 +/- 6.19 min; cold: men 42.88 +/- 11.79 min, boys 41.38 +/- 6.30 min), with no significant difference between men and boys (P > 0.05). Increases in rectal temperature, heart rate, and cardiac index were similar between groups and conditions. Stroke index, mean arterial pressure, and arterial venous oxygen difference were stable and similar in both conditions, without group differences. No significant dehydration was observed in men or boys. This study failed to reveal differences in exercise tolerance, thermoregulatory adaptation, or cardiovascular response to exercise in the heat between euhydrated prepubertal boys and adult men.