Response To Exercise Research Articles

Exercise-induced response of proteinogenic and non-proteinogenic plasma free amino acids is sport-specific: A comparison of sprint and endurance athletes.

Circulating blood is an important plasma free amino acids (PFAAs) reservoir and a pivotal link between metabolic pathways. No comparisons are available between athletes with opposite training adaptations that include a broader spectrum of both proteinogenic and non-proteinogenic amino acids, and that take into account skeletal muscle mass. We hypothesized that the levels of the exercise-induced PFAAs concentration are related to the type of training-related metabolic adaptation. We compared highly trained endurance athletes (n = 11) and sprinters (n = 10) aged 20‒35 years who performed incremental exercise until exhaustion. Venous blood was collected before and during the test and 30-min recovery (12 samples). Forty-two PFAAs were assayed using LC-ESI-MS/MS technique. Skeletal muscle mass was estimated using dual X-ray absorptiometry method. Glutamine and alanine were dominant PFAAs throughout the whole exercise and recovery period (~350‒650 μmol∙L-1). Total, combined proteinogenic, non-essential, and non-proteinogenic PFAAs levels were significantly higher in endurance athletes than sprinters (ANOVA group effects: p = 0.007, η2 = 0.321; p = 0.011, η2 = 0.294; p = 0.003, η2 = 0.376; p = 0.001, η2 = 0.471, respectively). The exercise response was more pronounced in endurance athletes, especially for non-proteinogenic PFAAs (ANOVA interaction effect: p = 0.038, η2 = 0.123). Significant between-group differences were observed for 19 of 33 PFAAs detected, including 4 essential, 7 non-essential, and 8 non-proteinogenic ones. We demonstrated that the PFAAs response to incremental aerobic exercise is associated with the type of training-related metabolic adaptation. A greater turnover and availability of circulating PFAAs for skeletal muscles and other body tissues is observed in endurance- than in sprint-trained individuals. Non-proteinogenic PFAAs, despite low concentrations, also respond to exercise loads, indicating their important, though less understood role in exercise metabolism. Our study provides additional insight into the exercise-induced physiological response of PFAAs, and may also provide a rationale in discussions regarding dietary amino acid requirements in high-performance athletes with respect to sports specialization.

Baseline Inflammation but not Exercise Modality Impacts Exercise-induced Kynurenine Pathway Modulation in Persons With Multiple Sclerosis: Secondary Results From a Randomized Controlled Trial.

The kynurenine pathway (KP) is an important hub in neuroimmune crosstalk that is dysregulated in persons with multiple sclerosis (pwMS) and modulated by exercise in a modality-specific manner. To compare changes in the KP metabolite profile of pwMS (1) following combined treatments including either high-intensity interval training (HIIT) or moderate-intensity continuous training (MICT) during a 3-week multimodal rehabilitation, (2) to evaluate exercise response in relation to baseline systemic inflammation, and (3) to investigate associations of kynurenines with physical capacity and clinical outcomes. For this secondary analysis of a randomized controlled trial, serum concentrations of kynurenines at baseline and after 3 weeks were determined using targeted metabolomics (LC-MS/MS). Exercise-induced changes in the KP metabolite profile according to treatment and baseline systemic inflammation (neutrophil-to-lymphocyte ratio (NLR) <3.12 versus ⩾3.12) were investigated using covariance analyses. Regardless of treatment, concentrations of tryptophan and most kynurenines decreased over time. Quinolinic acid concentration increased (p < .001). Participants with low and high NLR revealed differential exercise-induced changes in concentrations of kynurenines and NLR. The systemic inflammation markers neopterin (p = .015) and NLR (p < .001) decreased in the whole group and in participants with high NLR, respectively. Combined treatments including HIIT or MICT do not differentially modulate the KP metabolite profile, with both reducing concentrations of most kynurenines. Baseline systemic inflammation may impact exercise-induced changes in the KP metabolite profile and anti-inflammatory effects of exercise in pwMS. clinicaltrials.gov (identifier: NCT04356248).

Mechanisms of exercise intervention in type 2 diabetes: a bibliometric and visualization analysis based on CiteSpace.

Type 2 diabetes (T2D) is a common chronic metabolic disease, and its prevalence is increasing globally. Exercise is crucial for T2D management, yet many aspects of its mechanisms remain unclear. This study employs CiteSpace to reveal research hotspots and frontier issues in exercise intervention for T2D. A literature review spanning from January 1, 2013 to December 31, 2022, was conducted using the Web of Science Core Collection (WoSCC), with keywords including "exercise," "type 2 diabetes," and "mechanisms." We analyzed network diagrams generated by CiteSpace, which depicted relationships among countries, authors, and keywords. This study includes 1,210 English papers from 555 journals, affiliated with 348 institutions across 80 countries/regions. Notably, the United States, China, and the United Kingdom account for nearly half of all publications. The University of Copenhagen leads in publication volume, followed by Harvard Medical School and the University of Colorado. Key authors include Kirwan, John P (Case Western Reserve University), Malin, Steven K (Rutgers University), and Pedersen, Bente Klarlund (University of Copenhagen). Based on co-occurrence analysis of keywords, it is evident that terms such as "disease," "glucagon-like peptide 1," and "cardiovascular risk factor" exhibit high intermediary centrality. The analysis highlights ongoing investigations into molecular mechanisms, such as β-cell function enhancement, exerkines, and epigenetic mechanisms. Emerging areas include exercise response heterogeneity, circadian rhythm regulation, transcription factors, neurotrophic factors, and mitochondrial function. Future studies should prioritize understanding interactions between different exercise mechanisms and optimizing exercise prescriptions for T2D. Exercise prescriptions are crucial for effective interventions. Collaboration between countries and institutions is essential to understand the influences of different genetic backgrounds and environmental factors. Currently, a combination of aerobic and resistance training is considered the optimal form of exercise. However, considering time efficiency, high-intensity interval training (HIIT) has gained widespread attention and research due to its ability to achieve similar exercise effects in a shorter duration. Additionally, circadian rhythm regulation may affect the exercise outcomes of diabetic individuals at different times of the day, particularly concerning the specific types, doses, and intensities used for precision intervention in T2D.

Exploring sex differences in blood-based biomarkers following exhaustive exercise using bioinformatics analysis.

This study examined the acute effects of exercise testing on immunology markers, established blood-based biomarkers, and questionnaires in endurance athletes, with a focus on biological sex differences. Twenty-four healthy endurance-trained participants (16 men, age: 29.2± 7.6 years, maximal oxygen uptake ( ): 59.4 ± 7.5 ml · min-1 · kg-1; 8 women, age: 26.8 ± 6.1 years, : 52.9 ± 3.1 ml · min-1 · kg-1) completed an incremental submaximal exercise test and a ramp test. The study employed exploratory bioinformatics analysis: mixed ANOVA, k-means clustering, and uniform manifold approximation and projection, to assess the effects of exhaustive exercise on biomarkers and questionnaires. Significant increases in biomarkers (lymphocytes, platelets, procalcitonin, hemoglobin, hematocrit, red blood cells, cell-free DNA (cfDNA)) and fatigue were observed post-exercise. Furthermore, differences pre- to post-exercise were observed in cytokines, cfDNA, and other blood biomarkers between male and female participants. Three distinct groups of athletes with differing proportions of females (Cluster 1: 100% female, Cluster 2: 85% male, Cluster 3: 37.5% female and 65.5% male) were identified with k-means clustering. Specific biomarkers (e.g., interleukin-2 (IL-2), IL-10, and IL-13, as well as cfDNA) served as primary markers for each cluster, potentially informing individualized exercise responses. In conclusion, our study identified exercise-sensitive biomarkers and provides valuable insights into the relationships between biological sex and biomarker responses.

Cardiovascular benefits of moderate exercise: A comprehensive review of molecular and physiological mechanisms

This comprehensive review examines the cardiovascular benefits of moderate exercise, exploring the molecular and physiological mechanisms through which it reduces cardiovascular disease (CVD) risk. The study aimed to identify the specific ways in which moderate exercise improves cardiovascular health, focusing on key factors such as endothelial function, lipid metabolism, inflammation, and glucose homeostasis. A thorough review of existing literature was conducted to elucidate the mechanisms and impact of moderate exercise compared to other intensities. The findings highlight that moderate exercise optimizes cardiovascular health by enhancing nitric oxide production, reducing oxidative stress, and improving autonomic function, while also lowering blood pressure and cholesterol levels. Additionally, moderate exercise was shown to have anti-inflammatory effects, crucial for mitigating chronic conditions like atherosclerosis and diabetes-related cardiovascular complications. The review concludes that while high-intensity exercise offers rapid fitness improvements, moderate exercise is more accessible, safer, and sustainable for a broad population. Furthermore, it presents a promising non-pharmacological intervention for CVD prevention. Future research should explore individual variability in exercise responses, the role of skeletal muscle as a secretory organ, and the interaction between exercise and the gut microbiome. The study emphasizes the need for personalized exercise prescriptions and further investigation into the long-term benefits of exercise to optimize public health strategies. Keywords: Moderate Exercise, Cardiovascular Disease, Endothelial Function, Inflammation, Lipid Metabolism, Exercise Prescription.

Biomarkers in Endurance Exercise: Individualized Regulation and Predictive Value.

The high interindividual variability of exercise response complicates the efficient use of blood-based biomarkers in sports. To address this problem, a useful algorithm to characterize the individual regulation and predictive value of different candidate markers will be developed. Forty-nine participants completed two identical exercise trials. Blood samples were collected before, immediately after, 3 hours after, and 24 hours after completion of exercise. Plasma concentrations of interleukin (IL-) 1RA, IL-6, IL-8, IL-10, IL-15, creatine kinase (CK), cortisol, c-reactive protein (CRP), lactate dehydrogenase (LDH), and thiobarbituric acid reactive substances (TBARS) were measured. Individualized regulation was analyzed using k-means clustering and a Group Assignment Quality (GAQ) score. Regression trees with a bootstrapped-aggregated approach were used to assess the predictive qualities of the markers. For most of the markers studied, a distinction can be made between individuals who show a stronger or weaker response to a particular endurance training program. The regulation of IL-6, IL-8, IL-10, and CK exhibited a high degree of stability within the individuals. Regarding the predictive power of the markers, for all dependent variables, the most accurate predictions were obtained for cortisol and IL-8 based on the baseline value. For CK, a good prediction of recovery of maximal strength and subjective feeling of exhaustion can be made. For IL-1RA and TBARS, especially their reregulation can be predicted if the baseline level is known. Focusing individual variations in biomarker responses, our results suggest the combined use of IL-6, IL-8, IL-10, and CK for the personalized management of stress and recovery cycles following endurance exercise.

Interindividual response variation to exercise-based cardiac rehabilitation on changes in cardiorespiratory fitness in heart transplant patients: A secondary meta-analysis of randomized controlled trials

PurposeDetermine whether true inter-individual exercise response differences (IIRD) occur in cardiorespiratory fitness (CRF) as a result of exercise-based cardiac rehabilitation in heart transplant patients. MethodsUsing data from a recent (2023) meta-analysis of nine RCTs representing 296 patients (163 exercise, 133 control), an aggregate data meta-analysis of treatment effects (change outcome differences between exercise and control groups) was conducted as well as an IIRD meta-analysis using the inverse variance heterogeneity (IVhet) model. The primary outcome was cardiorespiratory fitness (VO2max) in mL.kg-1.min-1. ResultsStatistically significant and clinically important increases equivalent to 14.5% were observed for VO2max in mL.kg-1.min-1 (X̅, 3.0, 95% CI, 2.4 to 3.7 mL.kg-1.min-1, p <0.001; Q=11.8, p=0.16; I2=32.0%, 95% CI, 0% to 68.8%; τ2=0.4). The 95% prediction interval (PI) was 1.2 to 4.7 mL.kg-1.min-1. However, no statistically significant IIRD were observed (X̅, 0.6, 95% CI, -1.1 to 1.4 mL.kg-1.min-1; τ2=2.9). The 95% PI was -2.7 to 2.8 mL.kg-1.min-1. ConclusionsWhile exercise-based cardiac rehabilitation increases VO2max in mL.kg-1.min-1 in heart transplant patients, a lack of true exercise-associated IIRD exist. A need exists for additional well-designed randomized controlled trials of longer duration to determine the long-term effects of exercise-based cardiac rehabilitation on VO2max in mL.kg-1.min-1 among heart transplant patients.

Reduction of leptin levels during acute exercise is dependent on fasting but not on caloric restriction during chronic exercise: A systematic review and meta-analysis.

The importance of leptin in controlling body mass has recently gained more attention. Its levels are directly associated with the amount of fat mass, but not necessarily dependent on it. Exercise has great potential in reducing leptin levels, however the response of exercise to this cytokine is still not well understood. The objective of the review was to analyze the effects of physical exercise on plasma leptin concentration, either acutely (post-exercise/training session) and/or after a training period (short- or long-term), as well as to investigate the existence of possible moderating variables. The studies included in this systematic review were published between 2005 and May 2023. Only peer-reviewed studies, available in English, performed with humans that evaluated the effects of any form of exercise on leptin levels were included. The search was conducted on May 03, 2023, in Embase (Elsevier), MEDLINE via PubMed®, and Web of Science (Core collection). The risk of bias in the included trials was assessed by the Physiotherapy Evidence Database tool, considering 11 questions regarding the methodology of each study with 10 questions being scored. The data (n, mean, and standard deviation) were extracted from included studies to perform random effects meta-analyses using standardized mean difference between the pre- and post-intervention effects. Twenty-five studies (acute effect: 262 subjects; short- and long-term effect: 377 subjects) were included in this systematic review and meta-analysis. Short- and long-term physical exercise and caloric restriction plus exercise reduce plasma leptin levels, presenting statistically significant differences (p<0.001); as well as acute effect (p = 0.035), however the latter result was influenced by the pre-exercise meal as shown in the subgroup analysis. In this meta-analysis the effect of moderating factors on leptin reduction, not addressed by past reviews, is verified, such as the relationship with caloric restriction, exercise intensity and pre-exercise meal on acute responses. Both acute and chronic exercise reduce leptin levels, yet the acute effect is dependent on the pre-exercise meal. In addition to having a long-term reduction in leptin levels, the minimum amount of weekly exercise to have a significant reduction in plasma leptin is 180 minutes of moderate-intensity exercise and 120 minutes of high-intensity exercise.

Mechanisms of Exercise Intolerance Across the Breast Cancer Continuum: A Pooled Analysis of Individual Patient Data.

The purpose of this study is to evaluate the prevalence of abnormal cardiopulmonary responses to exercise and pathophysiological mechanism(s) underpinning exercise intolerance across the continuum of breast cancer (BC) care from diagnosis to metastatic disease. Individual participant data from four randomized trials spanning the BC continuum ([1] prechemotherapy [n = 146], [2] immediately postchemotherapy [n = 48], [3] survivorship [n = 138], and [4] metastatic [n = 47]) were pooled and compared with women at high-risk of BC (BC risk; n = 64). Identical treadmill-based peak cardiopulmonary exercise testing protocols evaluated exercise intolerance (peak oxygen consumption; V̇O2peak) and other resting, submaximal, and peak cardiopulmonary responses. The prevalence of 12 abnormal exercise responses was evaluated. Graphical plots of exercise responses were used to identify oxygen delivery and/or uptake mechanisms contributing to exercise intolerance. Unsupervised, hierarchical cluster analysis was conducted to explore exercise response phenogroups. Mean V̇O2peak was 2.78 ml O2.kg-1·min-1 (95% confidence interval [CI], -3.94, -1.62 mL O2.kg-1·min-1; P < 0.001) lower in the pooled BC cohort (52 ± 11 yr) than BC risk (55 ± 10 yr). Compared with BC risk, the pooled BC cohort had a 2.5-fold increased risk of any abnormal cardiopulmonary response (odds ratio, 2.5; 95% confidence interval, 1.2, 5.3; P = 0.014). Distinct exercise responses in BC reflected impaired oxygen delivery and uptake relative to control, although considerable inter-individual heterogeneity within cohorts was observed. In unsupervised, hierarchical cluster analysis, six phenogroups were identified with marked differences in cardiopulmonary response patterns and unique clinical characteristics. Abnormal cardiopulmonary response to exercise is common in BC and is related to impairments in oxygen delivery and uptake. The identification of exercise response phenogroups could help improve cardiovascular risk stratification and guide investigation of targeted exercise interventions.

Skeletal Muscle Gene Expression Signatures of Obese High and Low Responders to Endurance Exercise Training.

Exercise training is known to improve glucose tolerance and reverse insulin resistance in people with obesity. However, some individuals fail to improve or even decline in their clinical traits following exercise intervention. This study focused on gene expression and DNA methylation signatures in skeletal muscle of low (LRE) and high responders (RES) to 8 weeks of supervised endurance training. We performed skeletal muscle gene expression and DNA methylation analyses in LRE and RES before and after exercise intervention. Additionally, we applied the least absolute shrinkage and selection operator (LASSO) approach to identify predictive marker genes of exercise outcome. We show that the two groups differ markedly already before the intervention. RES were characterized by lower expression of genes involved in DNA replication and repair, and higher expression of extracellular matrix (ECM) components. The LASSO approach identified several novel candidates (eg, ZCWPW2, FOXRED1, STK40) that have not been previously described in the context of obesity and exercise response. Following the intervention, LRE reacted with expression changes of genes related to inflammation and apoptosis, RES with genes related to mitochondrial function. LRE exhibited significantly higher expression of ECM components compared to RES, suggesting improper remodeling and potential negative effects on insulin sensitivity. Between 45% and 70% of differences in gene expression could be linked to differences in DNA methylation. Together, our data offer an insight into molecular mechanisms underlying differences in response to exercise and provide potential novel markers for the success of intervention.

Value of exercise right heart catheterization for differential diagnosis of dyspnoea in chronic thromboembolic pulmonary disease

Abstract Background and Purpose Chronic thromboembolic disease (CTED) refers to chronic thrombotic pulmonary vascular occlusion in the absence of pulmonary hypertension (PH) at rest but functional limitation attributable to incipient vasculopathy. Our aim is to evaluate the hemodynamic response to exercise in patients with suspected CTED without relevant resting PH. Methods We prospectively included symptomatic patients with persistent pulmonary thrombosis despite optimal anticoagulant therapy for a minimum of 3 months. Patients with left heart disease and abnormal lung function tests were excluded. Patients included had mean pulmonary arterial pressure (mPAP ) ≤25 mmHg, pulmonary vascular resistance (PVR) &amp;lt; 3 WU and pulmonary arterial wedge pressure (PAWP) ≤15 mmHg. Exercise right heart catheterization (RHC) was performed via supine cycle ergometry. Exercise precapillary PH was defined as mPAP/CO slope &amp;gt;3 mmHg/l/min and PAWP/CO slope &amp;lt;2 mmHg/l/min. We made a subanalysis of those patients who fulfilled the new definition of resting PH (mPAP&amp;gt;20mmHg &amp; PVR &amp;gt; 2 WU) Results We studied 39 patients (mean age 52.7 ± 15.7 years, 36 % women): 12 of them met new resting PH criteria (mPAP &amp;gt; 20 mmHg &amp; RVP &amp;gt; 2 WU) , and 27 had normal resting hemodynamic. Baseline characteristics are summarized in Table 1 and did not reveal differences between groups except for haemodynamic parameters. From the entire cohort, 20 patients developed exercise PH: 14 (36%) with a precapillary pattern, and in 6 (15.4%) patients, the abnormal response was described as an abnormal PAWP/CO relationship during exercise. Exercise precapillary PH was documented in 67% of patients with resting PH according to the new PH criteria versus 37% of those without resting PH (Figure 1). Conclusion The functional limitation appears to be attributable to exercise precapillary PH in 36 % of patients with CTED suspicion and absence of significant resting PH. Exercise RHC is a valuable tool for diagnosing CTED and detecting other causes of dyspnoea, such as diastolic dysfunction. New resting PH haemodynamic criteria predict a higher percentage of abnormal exercise response, but one-third of patients develop exPH despite normal haemodynamic at rest.

Usefulness of cardiopulmonary exercise test to detect exercise pulmonary hypertension in the post pulmonary embolim follow-up

Abstract Functional impairment is largely reported after symptomatic pulmonary embolism (PE). Chronic thromboembolic pulmonary disease (CTED) refers to the presence of chronic thrombotic pulmonary vascular occlusion in the absence of pulmonary hypertension (PH) at rest but with incipient vasculopathy responsible for exercise limitation. Exercise haemodynamic studies have emerged to detect an abnormal response suggesting an established vasculopathy or an abnormal left ventricular filling pressure. We hypothesized that exercise intolerance due to an abnormal haemodynamic response during exercise might be unmasked by the parameters exhibited at the cardiopulmonary exercise test (CPET) in diagnostic workup after PE in symptomatic patients. Our aim was to correlate the values reached in the CPET pattern with haemodynamic response during exercise right heart catheterization (RHC) in patients with CTED suspicion. Methods We selected symptomatic patients with confirmed perfusion defects in lung scintigraphy despite optimal anticoagulant therapy for a minimum of 3 months after a PE with normal lung function tests. Left heart disease and significant PH were ruled out with RHC (inclusion criteria implied mean pulmonary arterial pressure (mPAP) &amp;lt; 25 mmHg and pulmonary vascular resistance (PVR) &amp;lt; 3 WU and pulmonary arterial wedge pressure (PAWP) ≤15 mmHg). Exercise RHC was performed sequentially 24 hours after CPET. The exercise protocol was the same for both tests. Pulmonary pressure and cardiac output (CO) were collected at each exercise leel. Exercise PH (ex-PH) was considered when mPAP/CO slope &amp;gt;3 mmHg·L−1·min−1. We made a subanalysis according to the new PH criteria (mPAP &amp;gt;20mmHg &amp; PVR &amp;gt; 2 WU at rest). Results 39 patients (median age 52.7 ± 15.7 years, 36% females) were included. 21 (53.8%) showed abnormal haemodynamic behaviour, 6(15.4%) of them due to abnormal PWAP/CO slope. Baseline characteristics are summarized in Table 1. Patients with abnormal exercise response showed worse ventilatory efficiency at exercise: 1) reduced partial end-tidal of carbon dioxide (PetCO2) at the anaerobic threshold (AT) (32.0 Vs 36.4, p=0.001), 2) a steeper VE/CO2 slope (35.6 Vs 30.9, p=0.009) and 3) a higher ventilatory equivalent for CO2 at the AT (35.5 Vs 31.6, p=0.004) compared to the group with normal hemodynamic behaviour. Oxygen consumption at the AT and peak oxygen consumption were slightly decreased without statistically significant differences between groups.Of the global cohort, 11 patients reached new resting PH criteria, and 92% of them showed ex-PH. Ventilatory efficiency showed differences in the subgroup with normal resting hemodynamic values, especially lower PetCO2 at the AT (31.8 Vs 35.0, p=0.008) (Figure 2). Conclusion In the context of persistent dyspnoea after PE, ventilatory inefficiency is a sign of exercise pulmonary hypertension, and CPET could identify patients with abnormal exercise response despite normal hemodynamic values at rest.

Association between aortic valve opening during exercise and right ventricular reserve in patients with left ventricular assist device

Abstract Background Aortic valve (AV) opening in patients after left ventricular (LV) assist device (LVAD) implantation is important to prevent adverse events. We hypothesised that right ventricular (RV) reserve function would play a crucial role to overcome pulmonary vascular resistance to ensure LV filling and AV opening in LVAD patients. However, detailed analysis between RV haemodynamic exercise response and AV opening with recent LVAD patients remains relatively unknown. Purpose The aim of this study was to explore the haemodynamic parameters observed during rest and maximal exercise and investigate the association of AV opening with RV reserve function and adverse events in patients with LVAD. Methods We prospectively examined 22 consecutive LVAD patients who were admitted to our university hospital between June 2020 and December 2022 after excluding those who were unable to perform exercise (n = 8). All patients underwent invasive exercise right heart catheterisation with simultaneous echocardiography in the supine position. AV status was assessed at rest and during exercise. RV stroke work index (RVSWI) was calculated as 0.0136 × stroke volume index × (mean pulmonary artery pressure – right atrial pressure) at rest and during exercise. RVSWI change from rest to peak exercise (ΔRVSWI) were calculated to evaluate RV reserve function. The patients were divided into three groups according to AV opening both rest and exercise (n = 6), AV opening only during exercise (n = 7), and AV closed both rest and exercise (n = 9). Results Patients were predominantly male (77%) and the median age was 51 (interquartile range [IQR] 39-63) years. There were no significant differences in age, sex, primary aetiology of heart failure, type of LVAD devices or echocardiographic parameters and RVSWI at rest among the groups. Patients with AV opening both rest and exercise, and only during exercise had significantly higher ΔRVSWI than those with AV closed both rest and exercise (Figure A). During a median follow-up period of 433 (IQR 228-558) days, adverse events occurred in six patients (27%), including one death, one hospitalisation for major bleeding, and four hospitalisations for right heart failure. Kaplan–Meier analysis revealed that the adverse events more frequently occurred in patients with AV closed both rest and exercise compared to those with AV opening (p = 0.014) (Figure B). Conclusions In patients with LVAD, AV opening at rest or during exercise was associated with preserved RV reserve function and less adverse events. These findings suggest that the observation of the AV opening during exercise would be useful for early identification of high-risk patients with LVAD. Further studies are needed to confirm our findings.

Effects of physical activity and exercise on Nucleobindin-2 gene expression and Nesfatin-1 concentration: A rapid review.

The aim of this rapid review is to examine the research evidence that presents the effects of physical activity and exercise on Nucleobindin-2 (NUCB2) gene expression and Nesfatin-1 concentration. Five databases (PubMed, Science Direct, Springer, Wiley, and Google Scholar) were searched for eligible studies from the earliest available date to August 2023. In human studies, Nesfatin-1 concentration either remains unchanged or increases after exercise training. It appears that higher exercise intensity and longer duration of training accentuate the increase of blood Nesfatin-1 concentration. The few human studies that have examined the acute response of exercise on Nesfatin-1 concentration from blood draws show conflicting results. There is a severe lack of biopsy studies in humans which warrants attention. All published animal studies have used the mouse model. The majority show that regular exercise training increases tissue NUCB2/Nesfatin-1. In some animal studies, where the effects of exercise on tissue Nesfatin-1 concentration has been seen as significant, there has been no significant effect of exercise on plasma Nesfatin-1 concentration. All animal studies evaluated the effect of endurance training except one which used resistance training. No animal studies have investigated the effects of acute exercise, which warrants investigation. In conclusion, human and animal studies have shown that physical training can increase NUCB2/Nesfatin-1, but research evidence examining the effect of acute exercise is in its infancy. In addition, future comparative studies are needed to compare the effects of different training protocols on NUCB2/Nesfatin-1 in humans and animals.

Proteomics and Precise Exercise Phenotypes in Heart Failure With Preserved Ejection Fraction: A Pilot Study.

While exercise impairments are central to symptoms and diagnosis of heart failure with preserved ejection fraction (HFpEF), prior studies of HFpEF biomarkers have mostly focused on resting phenotypes. We combined precise exercise phenotypes with cardiovascular proteomics to identify protein signatures of HFpEF exercise responses and new potential therapeutic targets. We analyzed 277 proteins (Olink) in 151 individuals (N=103 HFpEF, 48 controls; 62±11 years; 56% women) with cardiopulmonary exercise testing with invasive monitoring. Using ridge regression adjusted for age/sex, we defined proteomic signatures of 5 physiological variables involved in HFpEF: peak oxygen uptake, peak cardiac output, pulmonary capillary wedge pressure/cardiac output slope, peak pulmonary vascular resistance, and peak peripheral O2 extraction. Multiprotein signatures of each of the exercise phenotypes captured a significant proportion of variance in respective exercise phenotypes. Interrogating the importance (ridge coefficient magnitude) of specific proteins in each signature highlighted proteins with putative links to HFpEF pathophysiology (eg, inflammatory, profibrotic proteins),and novel proteins linked to distinct physiologies (eg, proteins involved in multiorgan [kidney, liver, muscle, adipose] health) were implicated in impaired O2 extraction. In a separate sample (N=522, 261 HF events), proteomic signatures of peak oxygen uptake and pulmonary capillary wedge pressure/cardiac output slope were associated with incident HFpEF (odds ratios, 0.67 [95% CI, 0.50-0.90] and 1.43 [95% CI, 1.11-1.85], respectively) with adjustment for clinical factors and B-type natriuretic peptides. The cardiovascular proteome is associated with precision exercise phenotypes in HFpEF, suggesting novel mechanistic targets and potential methods for risk stratification to prevent HFpEF early in its pathogenesis.

Arterial Stiffness and Cardiorespiratory Fitness Impairment in the Community.

Background During exercise, a healthy arterial system facilitates increased blood flow and distributes it effectively to essential organs. Accordingly, we sought to understand how arterial stiffening might impair cardiorespiratory fitness in community-dwelling individuals. Methods and Results Arterial tonometry and maximum effort cardiopulmonary exercise testing were performed on Framingham Heart Study participants (N=2898, age 54±9 years, 53% women, body mass index 28.1±5.3 kg/m2). We related 5 arterial stiffness measures (carotid-femoral pulse wave velocity [CFPWV]: a measure of aortic wall stiffness; central pulse pressure, forward wave amplitude, characteristic impedance: measures of pressure pulsatility; and augmentation index: a measure of relative wave reflection) to multidimensional exercise responses using linear models adjusted for age, sex, resting heart rate, habitual physical activity, and clinical risk factors. Greater CFPWV, augmentation index, and characteristic impedance were associated with lower peak oxygen uptake (VO2; all P<0.0001). We observed consistency of associations of CFPWV with peak oxygen uptake across age, sex, and cardiovascular risk profile (interaction P>0.05). However, the CFPWV-peak oxygen uptake relation was attenuated in individuals with obesity (P=0.002 for obesity*CFPWV interaction). Higher CPFWV, augmentation index, and characteristic impedance were also related to cardiopulmonary exercise testing measures reflecting adverse O2 kinetics and lower stroke volume and peripheral O2 extraction but not to ventilatory efficiency, a prognostic measure of right ventricular-pulmonary vascular performance. Conclusions Our findings delineate relations of arterial stiffness and cardiorespiratory fitness in community-dwelling individuals. Future studies are warranted to evaluate whether the physiological measures implicated here may represent potential targets for improving cardiorespiratory fitness in the general population.

Immunomodulatory effects of fucoidan in recreationally active adult males undertaking 3-weeks of intensified training

ABSTRACT The aim of the current study was to determine whether daily fucoidan supplementation (Undaria pinnatifida extract containing >85% fucoidan, 1 g/day) for three-weeks in a double blind-placebo controlled cross-over trial (ACTRN12621000872831) could modulate alterations in faecal (calprotectin, lysozyme and IgA) and salivary (lactoferrin, lysozyme and IgA) markers of mucosal immune competence typically observed in response to both acute physical activity, and a period of intensified exercise training, in healthy recreationally active men (n = 12). Participants responded positively to the intensified training with 16–19% improvement in mean power that was not different between supplement groups. Faecal biomarkers and concentrations of lactoferrin, lysozyme and IgA from resting saliva samples were largely stable over the supplementation period. Concentrations of salivary biomarkers varied significantly over time in response to acute exercise, however differences between supplementation groups were modest. For salivary lysozyme, there was a trend for a lower magnitude of increase post-exercise (p = 0.08) and limited return towards pre-exercise in response to fucoidan. For salivary IgA, a greater acute exercise response was noted for IgA in response to fucoidan (~2.7-fold higher; p = 0.02). Different dosage and supplementation protocols and inclusion of additional immune markers should be considered in subsequent assessments of any potential benefits of fucoidan supplementation in healthy active adults.

Physical exercise and cardiovascular response: design and implementation of a pediatric CMR cohort study

To examine feasibility and reproducibility and to evaluate the cardiovascular response to an isometric handgrip exercise in low-risk pediatric population using Cardiovascular Magnetic Resonance measurements. In a subgroup of 207 children with a mean age of 16 years participating in a population-based prospective cohort study, children performed an isometric handgrip exercise. During rest and exercise, continuous heart rate and blood pressure were measured. Cardiovascular magnetic resonance (CMR) measurements included left ventricular mass, aortic distensibility and pulse wave velocity at rest and left ventricular end-diastolic and end-systolic volumes, ejection fraction, stroke volume and cardiac output during rest and exercise. 207 children had successful CMR measurements in rest and 184 during exercise. We observed good reproducibility for all cardiac measurements. Heart rate increased with a mean ± standard deviation of 42.6% ± 20.0 and blood pressure with 6.4% ± 7.0, 5.4% ± 6.1 and 11.0% ± 8.3 for systolic, diastolic and mean arterial blood pressure respectively (p-values < 0.05). During exercise, left ventricular end-diastolic and end-systolic volumes and cardiac output increased, whereas left ventricular ejection fraction slightly decreased (p-values < 0.05). Stroke volume did not change significantly. A sustained handgrip exercise of 7 min at 30–40% maximal voluntary contraction is a feasible exercise-test during CMR in a healthy pediatric population, which leads to significant changes in heart rate, blood pressure and functional measurements of the left ventricle in response to exercise. This approach offers great novel opportunities to detect subtle differences in cardiovascular health.

Delayed metabolic disturbances in the myocardium after exertional heat stroke: contrasting effects of exertion and thermal load.

Epidemiological studies report higher risks of cardiovascular disease in humans exposed to heat stroke earlier in life. Previously, we explored mechanistic links between heat stroke and developing cardiac abnormalities using a preclinical mouse model of exertional heat stroke (EHS). Profound metabolic abnormalities developed in the ventricles of females but not males after 2 wk of recovery. Here we tested whether this lack of response in males could be attributed to the lower exercise performances or reduced thermal loads they experienced with the same running protocol. We systematically altered environmental temperature (Te) during EHS to manipulate heat exposure and exercise performance in the males. Three groups of adult C57BL/6 male mice were studied: "EHS-34" (Te = 34°C), "EHS-41" (Te = 41°C), and "EHS-39.5" (Te = 39.5°C). Mice ran until symptom limitation (unconsciousness), reaching max core temperature (Tc,max). After a 2-wk recovery, the mice were euthanized, and the ventricles were removed for untargeted metabolomics. Results were compared against age-matched nonexercise controls. The EHS-34 mice greatly elevated their exercise performance but reached lower Tc,max and lower thermal loads. The EHS-41 mice exhibited equivalent thermal loads, exercise times, and Tc,max compared with EHS-39.5. The ventricles from EHS-34 mice exhibited the greatest metabolic disturbances in the heart, characterized by shifts toward glucose metabolism, reductions in acylcarnitines, increased amino acid metabolites, elevations in antioxidants, altered TCA cycle flux, and increased xenobiotics. In conclusion, delayed metabolic disturbances following EHS in male myocardium appear to be greatly amplified by higher levels of exertion in the heat, even with lower thermal loads and max core temperatures.NEW & NOTEWORTHY Epidemiological data demonstrate greater cardiovascular risk in patients with previous heat stroke exposure. Using a preclinical mouse model of exertional heat stroke, male mice were exposed to one of three environmental temperatures (Te) during exercise. Paradoxically, after 2 wk, the mice in the lowest Te, exhibiting the largest exercise response and lowest heat load, had the greatest ventricular metabolic disturbances. Metabolic outcomes resemble developing left ventricular hypertrophy or stress-induced heart disease.

Implementation and Core Components of a Multimodal Program including Exercise and Nutrition in Prevention and Treatment of Frailty in Community-Dwelling Older Adults: A Narrative Review.

Increasing disability-free life expectancy is a crucial issue to optimize active ageing and to reduce the burden of evitable medical costs. One of the main challenges is to develop pragmatic and personalized prevention strategies in order to prevent frailty, counteract adverse outcomes such as falls and mobility disability, and to improve quality of life. Strong evidence reports the effectiveness of exercise interventions to improve various physical parameters and muscle function that are cornerstones of frailty. Other findings also suggest that the interactions between nutrition and physical exercise with or without health behavior promotion prevent the development of frailty. Multimodal programs, including structured exercise, adequate dietary intervention and health behavior promotion, appear increasingly consensual. However, in order for implementation in real-life settings, some pitfalls need to be addressed. In this perspective, structuring and tailoring feasible, acceptable and sustainable interventions to optimize exercise training responses are essential conditions to warrant short, medium and long-term individual benefits. The different components of exercise programs appear to be fairly consensual and effective. However, specific composition of the programs proposed (frequency, intensity, type, time, volume and progressiveness) have to be tailored to individual characteristics and objectives in order to improve exercise responses. The intervention approaches, behavioral strategies and indications for these programs also need to be refined and framed. The main objective of this work is to guide the actions of healthcare professionals and enable them to widely and effectively implement multimodal programs including exercise, nutrition and behavioral strategies in real-life settings.