Reduced Exercise Performance Research Articles

Interventricular abnormal septum displacement as contributory mechanism for impaired peak oxygen consumption and exercise cardiac output response in heart failure

Abstract Background In Heart failure (HF), the role of septum position and abnormal right ventricular (RV) geometry in determining exercise performance is unknown. Especially an abnormal interventricular septal (IVS) position is a well-known sign of RV pressure overload which affects left ventricular filling and output due to interdependence. Aim We postulated that an abnormal septum displacement during exercise and RV geometry alteration would affect peak exercise oxygen consumption (VO2) and cardiac output (CO) increase. Methods 17 HF patients with reduced ejection fraction (HFrEF) (mean age 71±12) underwent a cardiopulmonary exercise testing imaging (iCPET) with RV 3D-imaging analysis and were compared with a control population (mean age 67±14). 3D imaging of the RV chamber was examined off-line using the 4D RV TomTec software and obtained 3D mesh of the RV model using custom software to obtain the mean curvature value of IVS in 4 regions of: inflow tract (RVIT), outflow tract (RVOT), apical and body.We acquired measurements of curvature during end-diastole (ED) and at end systole (ES) phases and obtained a parametric curvature map. Results HF patients typically exhibited an abnormal of septal curve, with a more leftward configuration either at rest and under exercise (rest =−0.01±0.004 at ED, and −0.01±0.006 at ES; peak exercise= −0.01±0.004 at ED, and −0.01±0.004 at ES, Figure) compared to controls (rest=−0.02±0.003 at ED, and −0.02±0.005 at ES; peak exercise −0.02±0.008 at ED, and −0.03±0.006 at ES, Figure). Notably, the degree of the IVS curvature was found to linearly correlate with an impaired gas exchange performance as lower peak VO2 and a limited CO in HF (respectively r=0.62, p<0.001 and r=0.5, p<0.001 at ED during exercise; r=0.34, p<0.001 at ES during exercise, Figure). Conclusions In HF, the RV geometrical alterations reflected by an abnormal IVS displacement appear as novel contributory factors to a reduced exercise performance, impaired oxygen uptake and decreased CO.

Non-specific myocardial fibrosis in young competitive athletes: clinical significance and risk prediction by a powerful machine learning-based model.

Non-specific myocardial fibrosis (NSMF) is a heterogeneous entity. We aimed to evaluate young athletes with and without NSMF to establish potentially clinically significance. We analysed data from 328 young athletes. We identified 61 with NSMF and compared them with 75 matched controls. Athletes with NSMF were divided into Group 1 (n = 28) with 'minor' fibrosis and Group 2 (n = 33) with non-insertion point fibrosis, defined as 'major'. Athletes were followed-up for adverse events. Finally, we tested various machine learning (ML) algorithms to create a prediction model for 'major' fibrosis. We created 4 different classifiers. Athletes of black ethnicity were more likely to have a subepicardial pattern (OR: 5.0, p = 0.004). Athletes with 'major' fibrosis demonstrated a higher prevalence of lateral T-wave inversion (TWI) ( < 0.001) and ventricular arrhythmias (VEs > 500/24h, p = 0.046; non-sustained VT, p = 0.043). Athletes with 'minor' fibrosis demonstrated higher right ventricular volumes (p = 0.013), maximum Watts (p = 0.022) and maximum VO2 (p = 0.005). Lateral TWI (p = 0.026) and VO2 < 44mL/min/Kg (p = 0.040) remained the only significant predictors for 'major' fibrosis. During follow up, athletes with 'major' fibrosis were 9.1 times more likely to exhibit adverse events (OR 13.4, p = 0.041). All ML models outperformed the benchmark method in predicting significant MF, best accuracy achieved by the random forest classifier (90%). Lateral TWI and reduced exercise performance are associated with higher burden of fibrosis. Fibrosis was associated with increased ventricular arrhythmia and adverse events. A comprehensive assessment can help develop a ML-based model for significant fibrosis, which could also guide clinical practice and appropriate CMR referrals.

Phycocyanin attenuates skeletal muscle damage and fatigue via modulation of Nrf2 and IRS-1/AKT/mTOR pathway in exercise-induced oxidative stress in rats.

Prolonged strenuous exercise induces oxidative stress, leading to oxidative damage, skeletal muscle fatigue, and reduced exercise performance. The body compensates for oxidative stress through antioxidant actions, while related enzymes alone may not overcome excessive oxidative stress during prolonged strenuous exercise. Phycocyanin is an important antioxidant supplement derived from blue-green algae, which may be helpful in this type of situation. This study determined the effects of phycocyanin on exercise performance from prolonged strenuous exercise. Forty Sprague Dawley male rats were divided into 5 groups (n = 8 /group); Control group (C), Exercise group (E), and Exercise with supplement groups receiving low dose (Phycocyanin = 100 mg/kg BW; ELP) and high dose (Phycocyanin = 200 mg/kg BW; EHP) or vitamin C (Vitamin C = 200 mg/kg BW; VC). Phycocyanin was found to decrease oxidative damage markers, muscle fatigue, and muscle atrophy through the activated AKT/mTOR pathway. This was also found to have greater increases in antioxidants via Nrf2 signaling and increases ATP synthesis, GLUT4 transporters, and insulin signaling due to increased IRS-1/AKT signaling. In conclusion, phycocyanin was found to reduce oxidative damage and muscle atrophy, including an increase in insulin signaling in skeletal muscles leading to increased exercise performance in rats.

Abstract Mo101: 3-Mercaptopyruvate Sulfurtransferase is a Critical Regulator of Branched-Chain Amino Acid Catabolism in Cardiometabolic HFpEF

Background: Heart failure with preserved ejection fraction (HFpEF) is among the leading causes of cardiovascular mortality and morbidity. Recent multi-omics data sets underscore severely impaired branched-chain amino acid (BCAA) catabolism in the failing hearts of HFpEF patients. 3-mercaptopyruvate sulfurtransferase (3-MST) is a mitochondrial hydrogen sulfide (H 2 S) synthase that regulates mitochondrial biogenesis, function, and substrate metabolism. Research Questions and Goals: In the current study, we aimed to elucidate the role of 3-MST in myocardial BCAA catabolism in cardiometabolic HFpEF. Methods: 3-MST knockout or wild-type (WT) mice were subjected to control or L-NAME and high fat diet - induced HFpEF. Echocardiographic measurements, invasive hemodynamic assessment, and exercise capacity testing were conducted to determine HFpEF severity. Metabolomic analysis was performed to study BCAA catabolism. Additionally, a H 2 S donor, SG1002 was administered to increase H 2 S bioavailability in the setting of 3-MST deficiency and HFpEF. Results: We observed progressive deterioration in left ventricular (LV) diastolic function and exercise performance from mice subjected to HFpEF. Genetic ablation of 3-MST further-exacerbated HFpEF severity as evidenced by significantly increased E/e’ ratio, elevated LV end-diastolic pressure, and reduced exercise performance. Metabolomic analysis revealed pathological accumulation of intermediate metabolites of BCAA in the HFpEF hearts, suggesting a major derangement in myocardial BCAA catabolism. 3-MST KO hearts exhibited further BCAA catabolic defects as compared to those from WT. Importantly, H 2 S donor treatment significantly attenuated BCAA catabolic defect and alleviated HFpEF severity in both WT and 3-MST KO HFpEF mice. Conclusion: Our results demonstrate that deficiency of 3-MST impairs myocardial BCAA catabolism, which results in exacerbated HFpEF severity in a “two-Hit” mouse model of HFpEF. These data suggest 3-MST is critically involved in physiological substrate metabolism within the mitochondria and exerts beneficial effects in HFpEF. Future experiments are underway to delineate the mechanisms by which 3-MST regulates BCAA catabolism.

The Relationship between Inspiratory Muscle Strength and Cycling Performance: Insights from Hypoxia and Inspiratory Muscle Warm-Up.

Hypoxia increases inspiratory muscle work and consequently contributes to a reduction in exercise performance. We evaluate the effects of inspiratory muscle warm-up (IMW) on a 10 km cycling time trial in normoxia (NOR) and hypoxia (HYP). Eight cyclists performed four time trial sessions, two in HYP (FiO2: 0.145) and two in NOR (FiO2: 0.209), of which one was with IMW (set at 40% of maximal inspiratory pressure-MIP) and the other was with the placebo effect (PLA: set at 15% MIP). Time trials were unchanged by IMW (NORIMW: 893.8 ± 31.5 vs. NORPLA: 925.5 ± 51.0 s; HYPIMW: 976.8 ± 34.2 vs. HYPPLA: 1008.3 ± 56.0 s; p > 0.05), while ventilation was higher in HYPIMW (107.7 ± 18.3) than HYPPLA (100.1 ± 18.9 L.min-1; p ≤ 0.05), and SpO2 was lower (HYPIMW: 73 ± 6 vs. HYPPLA: 76 ± 6%; p ≤ 0.05). A post-exercise-induced reduction in inspiratory strength was correlated with exercise elapsed time during IMW sessions (HYPIMW: r = -0.79; p ≤ 0.05; NORIMW: r = -0.70; p ≤ 0.05). IMW did not improve the 10 km time trial performance under normoxia and hypoxia.

Adverse Effect of Bundle Branch Block on Exercise Performance in Patients with Fontan Physiology: From the Pediatric Heart Network Fontan Public Data Set.

Patients with Fontan physiology have reduced exercise performance compared to their peers as well as a higher incidence of bundle branch block (BBB). This study aims to investigate the association between BBB and exercise performance in the Fontan population through a retrospective review of the Pediatric Heart Network Fontan study public use dataset. "Low Performers" were defined as ≤ 25th percentile (for Fontan patients) for each exercise parameter at anaerobic threshold (AT) for gender and age and "Normal Performers" were all other patients. A total of 303 patients with Fontan physiology who underwent exercise testing reached AT and had complete data for BBB. BBB occurred more frequently in Low Performers for VO2 [OR (95% CI): 2.6 (1.4, 4.8)] and Work [OR (95% CI): 2.7 (1.4, 5.1)], suggesting that BBB in the Fontan population is associated with reduced exercise performance. This data adds to the existing clinical evidence of the adverse effects of conduction abnormalities on single ventricle cardiac output and adds support for consideration of cardiac resynchronization and multi-site ventricular pacing in this patient population.

Repeated Exposure to Mild Intermittent Hypoxia Improves Walking Endurance in OSA Patients for 4 - 8 Weeks Post Therapy

Background: Approximately one billion adults globally are diagnosed with obstructive sleep apnea (OSA). Co-morbidities associated with sleep apnea include hypertension and increased susceptibility to fatigue linked to lower oxygen bioavailability and reduced exercise performance. Previously, we reported that daily exposure to mild intermittent hypoxia (MIH) reduces blood pressure following 3 weeks of treatment. These reductions in pressure could be coupled with improvements in microvascular function, fatigability and exercise performance. Objective: Thus, in the present investigation we explored if daily exposure to MIH improves walking endurance that is sustained for 8 weeks following treatment in individuals with OSA and hypertension (HTN). We also examined if improvements in endurance were correlated to modifications in microvascular function measured using near-infrared spectroscopy. Methods: To achieve this objective, both males and females with severe OSA and hypertension were randomly assigned to receive an MIH intervention (n=9) or Sham MIH (n=10). Half of the individuals in each group were also randomly assigned to nightly CPAP use. Based on the small sample size and the similarity of responses, the groups treated with MIH or sham MIH were combined independent of CPAP use. The MIH protocol consisted of twelve 2-minute hypoxic episodes (PETO2 ~ 50 mmHg), interchanged with 2 minutes of normoxia administered each day for 15 days. PETCO2 was sustained 2 mmHg above baseline throughout the protocol. To evaluate the impact of MIH on microvascular function, oxygen carrying capacity and fatigability, 10 minute walk tests (10 MWT) and vascular occlusion tests coupled with near infrared spectroscopy (NIRS) were performed before therapy, as well as, 5 days, 4 weeks, and 8 weeks after therapy. Results: No significant difference in distance, speed, and performance fatigue was found between the two groups during the 10 MWT before therapy. However, following therapy, the MIH group was able to walk further (p = 0.005), faster (p = 0.005), and were less fatigued (p = 0.009). These improvements were maintained for up to 8 weeks following treatment with MIH but not sham MIH. As anticipated, the total distance travelled was correlated to the performance fatigue index (r = -0.734, p &lt; 0.0001). The Δ in performance fatigue index was correlated to the Δ in the maximal hyperemic response of oxygenated hemoglobin (HbO2) (r = -0.461, p = 0.021) following treatment with MIH. Likewise, the perceived fatigability index was correlated to the Δ in the amplitude of the hyperemic HbO2 response (relative to measures obtained at the end of occlusion) (r = -0.397, p = 0.0494) and the Δ in the time to achieve the maximum HbO2 hyperemic response (r = 0.412, p = 0.041) following treatment with MIH. Conclusion: Our results show that distance, speed and performance fatigue are improved following treatment with MIH and that these improvements are sustained for 8 weeks. Our results also showed that correlations between improved performance, perceived fatigue and microvascular function were evident, providing the impetus to further investigate these relationships. Overall, our findings suggest that MIH may improve muscle endurance, allowing individuals with OSA and HTN to walk faster, longer, and with less fatigue for up to 8 weeks following 15 days of treatment with MIH. I01CX000125, IK6CX002287, R01HL142757, R56HL142757. 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.

The Symptoms Experienced by Naturally Menstruating Women and Oral Contraceptive Pill Users and Their Perceived Effects on Exercise Performance and Recovery Time Posttraining

This study examined the type, frequency, and severity of symptoms experienced by naturally menstruating women and combined, monophasic, oral contraceptive pill users and their perceived effects on exercise performance and recovery time posttraining. Forty-two recreationally active women; 21 naturally menstruating and 21 combined, monophasic, oral contraceptive pill users participated in the study. Data were collected using two approaches: (a) an online 54-part retrospective survey and (b) a daily questionnaire. “Total number of symptoms,” “symptom index score,” “average symptom severity,” and “symptom index × severity score” were calculated from the retrospective data set. Real-time symptom data (i.e., “symptom frequency per phase” and “phase symptom frequency × severity score”) were calculated across predefined cycle phases from the daily questionnaire. The retrospective survey showed that symptoms were commonly reported by recreationally active women, but there were no differences in symptomology between the groups (p &gt; .113). The daily questionnaire showed both groups experienced a greater frequency and severity of symptoms while bleeding (p ≤ .001), which was associated with perceived reductions in exercise performance (odds ratio = 1.04–1.07) and a perceived longer recovery time posttraining (odds ratio = 1.03–1.04). The results from this study show that cycle-related symptoms were commonly reported by a group of recreationally active women, with no difference in symptomology between naturally menstruating women and combined, monophasic, oral contraceptive pill users. The magnitude of symptoms was greater while bleeding, which was associated with a perceived reduction in exercise performance and a longer recovery time posttraining.

Carbohydrate mouth rinse improves performance of mentally fatigued cyclists despite null effects on psychological responses

Mental fatigue reduces exercise performance through an impaired psychological response such as increased perceived exertion. Carbohydrate (CHO) mouth rinses improve exercise performance and perceived exertion likely due to an improved activation in cerebral reward areas, then we investigated if the CHO mouth rinse-improved exercise performance in mentally fatigued individuals was associated with ameliorated reward-related psychological responses. We hypothesised that CHO mouth rinse would be beneficial for mentally fatigued cyclists mainly in high-metabolic disturbance intensities. After familiarization and baseline sessions, well trained cyclists (n = 20) performed a maximal incremental test (MIT) after mental fatigue induction. They completed the MIT either without mouth rinse (MF) or rinsing their mouth with CHO (MF+CHO) or placebo (FM+PLA) solutions at every 25 % of the MIT. Psychological responses such as ratings of perceived exertion (RPE), affective valence, emotional arousal, and motivation were assessed throughout the MIT, while performance was assessed as peak power output and time of exercise. Mental fatigue reduced MIT performance (P < 0.05), but CHO mouth rinse was effective to counteract this deleterious mental fatigue effect (P < 0.05). However, we found null effects of CHO mouth rinses in psychological responses above the VT2 (P > 0.05) such as RPE, affective valence, emotional arousal, and motivation. Correlational analysis showed a significant, but moderate negative correlation between motivation and time of exercise above the VT2 when participants used CHO mouth rinse. In conclusion, the ergogenic CHO mouth rinse effects on MIT performance of mentally fatigued cyclists were irrespective of ameliorated psychological responses to exercise.

Iditarod, a Drosophila homolog of the Irisin precursor FNDC5, is critical for exercise performance and cardiac autophagy

Mammalian FNDC5 encodes a protein precursor of Irisin, which is important for exercise-dependent regulation of whole-body metabolism. In a genetic screen in Drosophila, we identified Iditarod (Idit), which shows substantial protein homology to mouse and human FNDC5, as a regulator of autophagy acting downstream of Atg1/Atg13. Physiologically, Idit-deficient flies showed reduced exercise performance and defective cold resistance, which were rescued by exogenous expression of Idit. Exercise training increased endurance in wild-type flies, but not in Idit-deficient flies. Conversely, Idit is induced upon exercise training, and transgenic expression of Idit in wild-type flies increased endurance to the level of exercise trained flies. Finally, Idit deficiency prevented both exercise-induced increase in cardiac Atg8 and exercise-induced cardiac stress resistance, suggesting that cardiac autophagy may be an additional mechanism by which Idit is involved in the adaptive response to exercise. Our work suggests an ancient role of an Iditarod/Irisin/FNDC5 family of proteins in autophagy, exercise physiology, and cold adaptation, conserved throughout metazoan species.

Severe pulmonary regurgitation does not influence exercise capacity in patients with repaired Tetralogy of Fallot

Abstract Funding Acknowledgements Type of funding sources: None. Background Identifying exercise determinants in patients with repaired Tetralogy of Fallot (rTOF) is complex. We sought to investigate exercise performance and to identify the best exercise predictors. Methods We prospectively recruited 100 patients with rTOF, 60 patients with severe PR (SPR), and 40 patients with no PR (control). All patients underwent cardiopulmonary exercise testing with echocardiography. Right ventricle (RV) contractile reserve (CR) was defined by the change in peak systolic velocity (ΔRVS’), and change in fractional area change (ΔFAC). Left ventricle (LV) CR was defined by the change in systolic function (ΔLVS’), and change in global longitudinal strain (ΔLVGLS). Results There was no significant difference in the reduced exercise performance between the SPR and control groups by peak absolute oxygen consumption VO2(1695±627 vs 1744±521, ml/min, p&amp;gt;0.05). During exercise, lower RV CR was observed in the SPR group by ΔRVS’ (41±28 vs 48±20%, p&amp;lt;0.05); and ΔFAC (20±15 vs 23±16, %, p&amp;lt;0.05), while it was greater for LV CR by ΔLVS’ (67±34 vs 61±28%, p&amp;lt;0.05). Change in ΔLVGLS was the same (15±17 vs 16±15, %, p&amp;gt;0.05). There were no associations between exercise measures with the degree of PR and RV volume at rest and during exercise. Augmentation of LVGLS and FAC demonstrated independent associations with peak VO2(r=.55, r=.45, p&amp;lt;0.05). Conclusions There was an overall marked reduction in exercise capacity, but no difference between those with and without PR. The degree of exercise limitation is more dependent upon the ability of RV and LV to augment longitudinal function rather than severity of PR.

Longitudinal Changes in Ventricular Mechanics in Adolescents After the Fontan Operation

Ventricular dysfunction is a significant clinical challenge in the long-term follow-up of patients with single-ventricle (SV) physiology. Ventricular function and myocardial mechanics can be studied using speckle-tracking echocardiography, which provides information on myocardial deformation. Limited information is available on serial changes in SV myocardial mechanics after the Fontan operation. The aim of this study was to describe serial changes in myocardial mechanics in children after the Fontan operation and the relationship of these changes with myocardial fibrosis markers as obtained by cardiac magnetic resonance and exercise performance parameters. The authors hypothesized that ventricular mechanics decline in patients with SVs over time and are associated with increased myocardial fibrosis and reduced exercise performance. A single-center retrospective cohort study including adolescents after the Fontan operation was conducted. Ventricular strain and torsion were assessed using speckle-tracking echocardiography. Cardiac magnetic resonance and cardiopulmonary exercise testing data closest to the latest echocardiographic examinations were performed. The most recent follow-up echocardiographic and cardiac magnetic resonance data were compared with those from sex- and age-matched control subjects and with individual patients' early post-Fontan data. Fifty patients with SVs (31 left ventricle, 13 right ventricle [RV], and six codominant) were included. Median time at follow-up echocardiography from the time of Fontan was 12.8years (interquartile range [IQR], 10.6 to 16.6years). Compared with early post-Fontan echocardiography, follow-up assessment showed reduced global longitudinal strain (-17.5% [IQR, -14.5% to -19.5%] vs -19.8% [IQR, -16.0% to -21.7%], P=.01], circumferential strain (-15.7% [IQR, -11.4% to -18.7%] vs -18.9% [IQR, -15.2% to -25.0%], P=.009), and torsion (1.28°/cm [IQR, 0.51°/cm to 1.74°/cm] vs 1.72°/cm [IQR, 0.92°/cm to 2.34°/cm], P=.02), with decreased apical rotation but no significant change in basal rotation. Single RVs had lower torsion compared with single left ventricles (1.04°/cm [IQR, 0.12°/cm to 2.20°/cm] vs 1.25°/cm [IQR, 0.25°/cm to 2.51°/cm], P=.01). T1 values were higher in patients with SV compared with control subjects (1,009±36 vs 958±40msec, P=.004) and in those with single RVs compared with single left ventricles (1,023±19 vs 1,006±17msec, P=.02). T1 was correlated with circumferential strain (r=0.59, P=.04) and inversely correlated with O2 saturation (r=-0.67, P<.001) and torsion (r=-0.71, P=.02). Peak oxygen consumption was correlated with torsion (r=0.52, P=.001) and untwist rates (r=0.23, P=.03). After the Fontan procedures, there is a progressive decrease in myocardial deformation parameters. The progressive decrease in SV torsion is related to a decrease in apical rotation, which is more pronounced in single RVs. Decreased torsion is associated with increased markers of myocardial fibrosis and lower maximal exercise capacity. Torsional mechanics may be an important parameter to monitor after Fontan palliation, but further prognostic information is required.

Skeletal muscle delimited myopathy and verapamil toxicity in SUR2 mutant mouse models of AIMS

ABCC9‐related intellectual disability and myopathy syndrome (AIMS) arises from loss‐of‐function (LoF) mutations in the ABCC9 gene, which encodes the SUR2 subunit of ATP‐sensitive potassium (KATP) channels. KATP channels are found throughout the cardiovascular system and skeletal muscle and couple cellular metabolism to excitability. AIMS individuals show fatigability, muscle spasms, and cardiac dysfunction. We found reduced exercise performance in mouse models of AIMS harboring premature stop codons in ABCC9. Given the roles of KATP channels in all muscles, we sought to determine how myopathy arises using tissue‐selective suppression of KATP and found that LoF in skeletal muscle, specifically, underlies myopathy. In isolated muscle, SUR2 LoF results in abnormal generation of unstimulated forces, potentially explaining painful spasms in AIMS. We sought to determine whether excessive Ca2+ influx through CaV1.1 channels was responsible for myopathology but found that the Ca2+ channel blocker verapamil unexpectedly resulted in premature death of AIMS mice and that rendering CaV1.1 channels nonpermeable by mutation failed to reverse pathology; results which caution against the use of calcium channel blockers in AIMS.

Myocardial viscoelasticity impairs late-filling in working myocardial slice preparations.

Heart failure with preserved ejection fraction (HFpEF) is linked to diabetes and obesity and has become the dominant form of heart failure in western cultures. Both impaired relaxation and increased myocardial stiffness impede ventricular filling which manifests in patients as exercise intolerance early in disease progression. The observation of elevated end-diastolic pressure (EDP) in exercising HFpEF patients implies that the passive viscoelasticity of the heart may reduce exercise performance, but no direct experimental methods can assess this ex-vivo. To determine if the passive viscoelastic properties of the myocardium were capable of influencing EDP in exercise, we have developed a myocardial slice-based protocol that permits long-duration mechanical testing with controllable end-diastolic filling velocity. The role of myocardial viscoelasticity on work output is determined by conducting work-loops at varying speeds of end-diastolic filling. Our results demonstrate an increase in the slope of the end diastolic pressure volume relationship (EDPVR) with filling speed in healthy Wistar-Kyoto rats (WKY) suggesting viscoelasticity can limit myocardial filling ex-vivo. To determine if the viscoelastic contribution was predominantly due to myocytes or extracellular matrix (ECM), the passive mechanical properties of the tissue were assessed before and after decellularization. The results indicate that in WKY rats, the ECM contributes minimally to tissue performance under the experimental working conditions. Together, these results suggest that increased myocardial viscoelasticity may contribute to diastolic dysfunction through myocyte stiffening in the absence of overt fibrosis.

12-week curcumin supplementation may relieve postexercise muscle fatigue in adolescent athletes.

High-intensity exercise causes oxidative stress, muscle soreness, and muscle fatigue, leading to reduced exercise performance. Curcumin possesses antioxidative and anti-inflammatory properties and thus alleviates postexercise damage. Therefore, this study evaluated the effect of curcumin on athletes' postexercise recovery. A non-randomized prospective cohort investigation was done. We recruited middle and high school athletes engaged in wrestling, soccer, and soft tennis. During the 12-week daily exercise training, the participants were assigned to receive curcumin supplementation (curcumin group) or not (control group). Body composition, exercise performance, inflammatory factors, muscle fatigue, and muscle soreness were recorded at the baseline and end of the study. We used the Mann-Whitney U test to compare the participants' demographics, such as age, height, weight, and training years. The Wilcoxon test was used to compare the differences between the groups before and after curcumin supplementation. Of 28 participants (21 men and 7 women, with a mean age of 17 years), 13 were in the curcumin group and 15 in the control group. A significant decrease in muscle fatigue and muscle soreness scores was observed in the curcumin group after 12 weeks. Moreover, a significant decrease in the 8-hydroxy-2 deoxyguanosine level and a significant increase in basic metabolic rate and fat-free mass were observed in the curcumin group. Curcumin can reduce muscle fatigue and soreness after exercise, indicating its potential to alleviate postexercise damage. It could be considered to cooperate with nutritional supplements in regular training in adolescent athletes.

841 ASSOCIATION BETWEEN CARDIORESPIRATORY SYMPTOMS AND LUNG FUNCTION IN PATIENTS WITH LONG-COVID SIGNS

Abstract Background Many patients recovered from COVID-19 infection present a variety of symptoms which limits overall quality of life, as reduced exercise performance, dysfunctional breathing, cough, dyspnea, weakness and anxiety. This condition has been named long COVID. The origin of this symptomatology is still unclear. This study has the aim to analyse the relation between symptoms and respiratory function, focusing on the alveolar capillary membrane. Methods Consecutive patients with long COVID 19 symptoms after 6 months were included. Patients underwent full clinical evaluation, laboratory tests, echocardiography, thoracic CT scan, spirometry including alveolar capillary membrane diffusion by means of combined carbon dioxide and nitric oxide lung diffusion (DLCO/DLNO) and cardiopulmonary exercise test. We measured surfactant derive protein B (immature form) as blood marker of alveolar capillary function. A questionnaire allowed to evaluate symptoms. Results We evaluated 204 post COVID-19 patients (age 56.5±14.5 y, 89 females (44%), BMI 25.7±4.0, 6% active smokers) referring to our hospital 171±85 days after the end of acute COVID-19 infection (Fig. 1). None of spirometry data was associated with long COVID 19 referred symptoms. SPB was not associated to differences in any of the referred symptoms. Subjects with lower capillary volume (VCap) have more frequently dyspnea, tiredness, fatigability and hair loss (Fig.2). CT scan lung damage correlated with SPB and membrane diffusion but not with VCap, exercise performance or VE/VCO2 slope. The strongest correlation of SPB were with lung parenchyma damage and Vcap. Conclusions Our data suggest that a relevant reduction of alveolar capillary membrane function plays a central role in the long COVID cardiorespiratory symptoms.

P.82 Case-Control cardiopulmonary exercise testing for patients with neuromuscular disease

Patients with neuromuscular diseases (NMD) present with disease-specific muscle weakness and fatigue and are largely sedentary and deconditioned. This sedentary lifestyle leads to additional weakness, fatigue and loss of function. This deconditioning cycle results in reduced cardiorespiratory fitness (CRF), which is strongly related to increased risk for cardiovascular and pulmonary diseases (e.g. hypertension, diabetes mellitus, coronary artery disease, chronic obstructive pulmonary disease). These largely preventable diseases are the leading causes of morbidity and mortality for those with and without NMD. The gold standard for the assessment of CRF is peak oxygen consumption (peak VO2), assessed with cardiopulmonary exercise testing (CPX). Several small studies have suggested a role for CPX for patients with NMD, who present with hyperventilatory and hypercirculatory patterns, but with inconsistent results. We performed CPX in 37 patients with NMD and 8 controls using a Keiser wheelchair accessible total body trainer and a CosMed K5 wearable metabolic system. We were able to perform high quality CPX by both subjective and objective measures. Compared to controls, individuals with NMD presented with reduced exercise performance as measured by peak wattage and peak VO2. Disturbed hemodynamic and ventilatory patterns were noted, with borderline chronotropic incompetence and low O2 pulse, early and marked ventilatory inefficiency and severely reduced oxygen uptake efficiency slope and a high proportion of patients displaying exercise oscillatory breathing. Importantly, we observed that relative effort as illustrated by equivalent RPE and RER was not significantly different than controls. Our data illustrate that high quality CPX can be conducted in this population and suggest that performing CPX in patients with NMD will reveal distinct physiological profiles that may lead to a better understanding of cardiopulmonary and metabolic pathology in these individuals.

Exercise Performance In Sport-related Concussion Is Not Limited By Peripheral Cardiovascular Function

PURPOSE: Exercise intolerance is a hallmark of sport-related concussion (SRC) and there is growing evidence for using aerobic exercise to treat concussed adolescents. It is not known if the limitation to exercise performance after concussion is central (i.e., altered cerebral blood flow regulation) or peripheral (i.e., cardiovascular limitation of oxygen delivery to muscles). We examined aspects of pulmonary, cardiac and vascular function during cycle exercise in concussed adolescents within days of injury and again upon clinical recovery. METHODS: 26 concussed adolescents (age 15.42 ± 1.1.4 y, 46.5% female) presenting within 10 days of concussion and 24 age and sex matched healthy controls (age 15.83 ± 1.55 y, 41.7% female) were included. Concussed participants completed the Buffalo Concussion Bike Test (BCBT) within 1 week of injury and once after clinical recovery. Controls completed the test twice, 4-6 weeks apart. Respiratory and cardiovascular measures were recorded each minute during the BCBT. RESULTS: Heart rate (146.90 vs 144.89 bpm), stroke volume (115.25 vs 108.13 cm3), cardiac output (16.57 vs 15.89 L/min), ventilation (0.65 vs 0.61 L/sec), and VO2 (20.24 vs 20.17 L/kg/min) were not significantly different between concussed participants and controls at any time during exercise. There were statistically significant but small, not clinically meaningful, differences in diastolic and systolic blood pressure at various time points between concussed and healthy participants. CONCLUSION: Acutely concussed adolescent athletes did not differ significantly from healthy controls, or after recovery, in their cardiovascular responses to a graded exercise bike test that measured their exercise tolerance after SRC. Importantly, there was no physiological evidence of aerobic deconditioning in the concussed athletes within 10 days of their injury. The data suggest that the reduced exercise performance (i.e., exercise intolerance) of concussed adolescent athletes within 10 days of SRC is not from limited peripheral oxygen delivery to exercising muscles and that concussed athletes are not aerobically deconditioned during the timeframe that early exercise treatment is being prescribed.

Curcumin: A dietary phytochemical for boosting exercise performance and recovery.

Curcumin, as the main natural compound in the turmeric plant (Curcuma longa), is a yellowish polyphenol that has been used traditionally in Asian countries as a medicinal herb for various types of disease and pathological conditions caused by inflammation and oxidative stress. In the present review, we conducted a comprehensive literature search for evidence that shows the effect of curcumin on factors influencing exercise performance, including muscle damage, muscle soreness, inflammation, and oxidative stress. During exercise, reactive oxygen species and inflammation are increased. Thus, if there is no balance between endogenous and exogenous antioxidants and increases in oxidative stress and inflammation, which is important for maintaining redox homeostasis in skeletal muscle, it can lead to muscle soreness and muscle damage and ultimately result in reduced exercise performance. Due to the anti-oxidant and anti-inflammatory properties of curcumin, it can increase exercise performance and decrease exercise-induced muscle soreness and muscle damage. It appears that curcumin supplementation can have positive effects on exercise performance and recovery, muscle damage and pain, inflammation, and oxidative stress. However, there is still a need to precisely evaluate factors to more accurately assess/quantify the beneficial therapeutic effects of curcumin with regard to enhancing exercise performance and recovery.

Influence of continuous inspiratory resistive breathing trials on corticospinal excitability of lower limb muscles during isometric contraction

ABSTRACT BACKGROUND Increased work of breathing or fatigue of respiratory muscles has been suggested to reduce exercise performance. PURPOSE The present study investigated the effects of continuous inspiratory resistive breathing (IRB) on the responsiveness of corticospinal pathway innervating the vastus lateralis (VL) to determine whether respiratory muscle fatigue affects the central motor output to exercising limb muscles. METHODS Eight subjects underwent a 6-min IRB trial three times (IRB1–3) in two experiments. During each IRB trial, the subjects performed voluntary hyperventilation through a mask attached with an inspiratory resistive load (approximately 30% of maximal inspiratory pressure (PImax)). In Experiment 1, PImax was measured at baseline and after each IRB trial. In Experiment 2, VL responses to transcranial magnetic stimulation (motor evoked potentials (MEPs) and cortical silent periods were assessed during 5 s isometric knee extension at an intensity of 15% of the maximal voluntary contraction over the same time course as in Experiment 1. RESULTS PImax decreased from baseline after IRB2 and IRB3 (P < 0.05). MEPs increased from baseline after IRB1 and IRB2 (P < 0.05), whereas MEPs after IRB3 were not significantly different from baseline. Cortical silent periods did not change from baseline after IRB1 and IRB2, whereas cortical silent periods after IRB3 increased from baseline (P < 0.05). CONCLUSION These results suggest that as inspiratory muscle fatigue progresses, the corticospinal tract controlling the lower limb muscles can shift from excitatory dominance to inhibitory dominance as a whole, affecting the central motor output to working limb muscles.