Discordant skeletal muscle gene and protein responses to exercise.

The ability of skeletal muscle to adapt to repeated contractile stimuli is one of the most intriguing aspects of physiology. The molecular bases underpinning these adaptations involve increased protein activity and/or expression, mediated by an array of pre- and post-transcriptional processes, as well as translational and post-translational control. A longstanding dogma assumes a direct relationship between exercise-induced increases in mRNA levels and subsequent changes in the abundance of the proteins they encode. Drawing on the results of recent studies, we dissect and question the common assumption of a direct relationship between changes in the skeletal muscle transcriptome and proteome induced by repeated muscle contractions (e.g., exercise).

Exercise Inhibits Doxorubicin-Induced Cardiotoxicity via Regulating B Cells.

BACKGROUND: Doxorubicin is an effective chemotherapeutic agent, but its use is limited by acute and chronic cardiotoxicity. Exercise training has been shown to protect against doxorubicin-induced cardiotoxicity, but the involvement of immune cells remains unclear. This study aimed to investigate the role of exercise-derived B cells in protecting against doxorubicin-induced cardiotoxicity and to further determine whether B cell activation and antibody secretion play a role in this protection. METHODS: Mice that were administered with doxorubicin (5 mg/kg per week, 20 mg/kg cumulative dose) received treadmill running exercise. The adoptive transfer of exercise-derived splenic B cells to µMT-/- (B cell-deficient) mice was performed to elucidate the mechanism of B cell regulation that mediated the effect of exercise. RESULTS: Doxorubicin-administered mice that had undergone exercise training showed improved cardiac function, and low levels of cardiac apoptosis, atrophy, and fibrosis, and had reduced cardiac antibody deposition and proinflammatory responses. Similarly, B cell pharmacological and genetic depletion alleviated doxorubicin-induced cardiotoxicity, which phenocopied the protection of exercise. In vitro performed coculture experiments confirmed that exercise-derived B cells reduced cardiomyocyte apoptosis and fibroblast activation compared with control B cells. Importantly, the protective effect of exercise on B cells was confirmed by the adoptive transfer of splenic B cells from exercised donor mice to µMT-/- recipient mice. However, blockage of Fc gamma receptor IIB function using B cell transplants from exercised Fc gamma receptor IIB-/- mice abolished the protection of exercise-derived B cells against doxorubicin-induced cardiotoxicity. Mechanistically, we found that Fc gamma receptor IIB, an important B cell inhibitory receptor, responded to exercise and increased B cell activation threshold, which participated in exercise-induced protection against doxorubicin-induced cardiotoxicity. CONCLUSIONS: Our results demonstrate that exercise training protects against doxorubicin-induced cardiotoxicity by upregulating Fc gamma receptor IIB expression in B cells, which plays an important anti-inflammatory role and participates in the protective effect of exercise against doxorubicin-induced cardiotoxicity.

2024 ACC/AHA/AACVPR/APMA/ABC/SCAI/SVM/SVN/SVS/SIR/VESS Guideline for the Management of Lower Extremity Peripheral Artery Disease: A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines.

AIM: The "2024 ACC/AHA/AACVPR/APMA/ABC/SCAI/SVM/SVN/SVS/SIR/VESS Guideline for the Management of Lower Extremity Peripheral Artery Disease" provides recommendations to guide clinicians in the treatment of patients with lower extremity peripheral artery disease across its multiple clinical presentation subsets (ie, asymptomatic, chronic symptomatic, chronic limb-threatening ischemia, and acute limb ischemia). METHODS: A comprehensive literature search was conducted from October 2020 to June 2022, encompassing studies, reviews, and other evidence conducted on human subjects that was published in English from PubMed, EMBASE, the Cochrane Library, CINHL Complete, and other selected databases relevant to this guideline. Additional relevant studies, published through May 2023 during the peer review process, were also considered by the writing committee and added to the evidence tables where appropriate. STRUCTURE: Recommendations from the "2016 AHA/ACC Guideline on the Management of Patients With Lower Extremity Peripheral Artery Disease" have been updated with new evidence to guide clinicians. In addition, new recommendations addressing comprehensive care for patients with peripheral artery disease have been developed.

Nuclear-localized androgen receptor content following resistance exercise training is associated with hypertrophy in males but not females.

Androgen receptor (AR) content has been implicated in the differential response between high and low responders following resistance exercise training (RET). However, the influence of AR expression on acute skeletal muscle damage and whether it may influence the adaptive response to RET in females is poorly understood. Thus, the purpose of this exploratory examination was to 1) investigate changes in AR content during skeletal muscle repair and 2) characterize AR-mediated sex-based differences following RET. A skeletal muscle biopsy from the vastus lateralis was obtained from 26 healthy young men (n = 13) and women (n = 13) at baseline and following 300 eccentric kicks. Subsequently, participants performed 10 weeks of full-body RET and a final muscle biopsy was collected. In the untrained state, AR mRNA expression was associated with paired box protein-7 (PAX7) mRNA in males. For the first time in human skeletal muscle, we quantified AR content in the myofiber and localized to the nucleus where AR has been shown to trigger cellular outcomes related to growth. Upon eccentric damage, nuclear-associated AR (nAR) content increased (p < .05) in males and not females. Males with the greatest increase in cross-sectional area (CSA) post-RET had more (p < .05) nAR content than females with the greatest gain CSA. Collectively, skeletal muscle damage and RET increased AR protein, and both gene and hypertrophy measures revealed sex differences in relation to AR. These findings suggest that AR content but more importantly, nuclear localization, is a factor that differentiates RET-induced hypertrophy between males and females.

Exercise therapy for chronic symptomatic peripheral artery disease.

All guidelines worldwide strongly recommend exercise as a pillar of the management of patients affected by lower extremity peripheral artery disease (PAD). Exercise therapy in this setting presents different modalities, and a structured programme provides optimal results. This clinical consensus paper is intended for clinicians to promote and assist for the set-up of comprehensive exercise programmes to best advice in patients with symptomatic chronic PAD. Different exercise training protocols specific for patients with PAD are presented. Data on patient assessment and outcome measures are narratively described based on the current best evidence. The document ends by highlighting disparities in access to supervised exercise programmes across Europe and the series of gaps for evidence requiring further research.

Coronary artery disease management in older adults: revascularization and exercise training.

The mean age of patients with coronary artery disease (CAD) is steadily increasing. In older patients, there is a tendency to underutilize invasive approach, coronary revascularization, up-to-date pharmacological therapies, and secondary prevention strategies, including cardiac rehabilitation. Older adults with CAD commonly exhibit atypical symptoms, multi-vessel disease involvement, complex coronary anatomy, and a higher presence of risk factors and comorbidities. Although both invasive procedures and medical treatments are characterized by a higher risk of complications, avoidance may result in a suboptimal outcome. Often, overlooked factors, such as coronary microvascular disease, malnutrition, and poor physical performance, play a key role in determining prognosis, yet they are not routinely assessed or addressed in older patients. Historically, clinicians have relied on sub-analyses or observational findings to make clinical decisions, as older adults were frequently excluded or under-represented in clinical studies. Recently, dedicated evidence through randomized clinical trials has become available for older CAD patients. Nevertheless, the management of older CAD patients still raises several important questions. This review aims to comprehensively summarize and critically evaluate this emerging evidence, focusing on invasive management and coronary revascularization. Furthermore, it seeks to contextualize these interventions within the framework of improved risk stratification tools for older CAD patients, through user-friendly scales along with emphasizing the importance of promoting physical activity and exercise training to enhance the outcomes of invasive and medical treatments. This comprehensive approach may represent the key to improving prognosis in the complex and growing patient population of older CAD patients.

Chronotropic Incompetence among People with HIV Improves with Exercise Training in the Exercise for Healthy Aging Study.

BACKGROUND: People with HIV (PWH) have lower exercise capacity compared to peers without HIV, which may be explained by chronotropic incompetence (CI), the inability to increase heart rate during exercise. METHODS: The Exercise for Healthy Aging Study included adults ages 50-75 with and without HIV. Participants completed 12 weeks of moderate intensity exercise, before randomization to moderate or high intensity for 12 additional weeks. We compared adjusted heart rate reserve (AHRR; CI <80%) on cardiopulmonary exercise testing by HIV serostatus and change from baseline to 12 and 24 weeks using mixed effects models. RESULTS: Among 32 PWH and 37 controls (median age 56, 7% female, mean BMI 28 kg/m2), 28% of PWH compared to 11% of controls had CI at baseline (p = 0.067). AHRR was lower among PWH (91 vs 101%; difference 10%, 95% CI 1.9-18.9; p = 0.02). At week 12, AHRR normalized among PWH (+8%, 95% CI 4-11; p < 0.001) and was sustained at week 24 (+5, 95%CI 1-9; p = 0.008) compared to no change among controls (95%CI -4 to 4; p = 0.95; pinteraction = 0.004). After 24 weeks of exercise, only 15% PWH and 10% of controls had CI (p = 0.70). CONCLUSIONS: Chronotropic incompetence contributes to reduced exercise capacity among PWH and improves with exercise training.

Genome-wide Association Study of Exercise-induced Skeletal Muscle Hypertrophy and the Construction of Predictive Model.

To investigate inter-individual differences in muscle thickness of Rectus Femoris (MTRF) following 12 weeks of Resistance Training (RT) or High-Intensity Interval Training (HIIT) to explore the genetic architecture underlying skeletal muscle hypertrophy and to construct predictive models. We conducted musculoskeletal ultrasound assessments of the MTRF response in 440 physically inactive adults after the 12-week exercise period. A Genome-wide Association study (GWAS) was employed to identify variants associated with MTRF response, separately for RT and HIIT. Utilizing polygenic predictor score (PPS), we estimated the genetic contribution to exercise-induced hypertrophy. Predictive models for MTRF response were constructed using Random Forest (RF), Support Vector Mac (SVM), and Generalized Linear Model (GLM) in 10 cross-validated approach. MTRF increased significantly after both RT (8.8%, P<0.05) and HIIT (5.3%, P<0.05), but with considerable inter-individual differences (RT: -13.5~38.4%, HIIT: -14.2%~30.7%). Eleven lead SNPs in RT and eight lead SNPs in HIIT were identified at a significance level of P<1×10-5. The PPS was associated with MTRF response, explaining 47.2% of the variation in response to RT and 38.3% of the variation in response to HIIT. Notably, the GLM and SVM predictive models exhibited superior performance in comparison to RF models (p<0.05), and the GLM demonstrated optimal performance with an AUC of 0.809 (95%CI:0.669-0.949). Factors such as PPS, baseline MTRF, and exercise protocol exerted influence on the MTRF response to exercise, with PPS being the primary contributor. The GLM and SVM predictive model, incorporating both genetic and phenotypic factors, emerged as promising tools for predicting exercise-induced skeletal muscle hypertrophy.

Exercise training alters skeletal muscle microvascular endothelial cell properties in recent postmenopausal females.

The present study examined and compared the impact of exercise training on redox and molecular properties of human microvascular endothelial cells derived from skeletal muscle biopsies from sedentary recent (RPF, ≤ 5 years as postmenopausal) and late (LPF, ≥ 10 years as postmenopausal) postmenopausal females. Resting skeletal muscle biopsies were obtained before and after 8 weeks of intense aerobic exercise training for isolation of microvascular endothelial cells and determination of skeletal muscle angiogenic proteins and capillarisation. The microvascular endothelial cells were analysed for mitochondrial respiration and production of reactive oxygen species (ROS), glycolysis and proteins related to vascular function, redox balance and oestrogen receptors. Exercise training led to a reduced endothelial cell ROS formation (∼50%; P = 0.009 and P = 0.020 for intact and permeabilized cells (state 3), respectively) in RPF only, with no effect on endothelial mitochondrial capacity in either group. Basal endothelial cell lactate formation was higher (7%; P = 0.028), indicating increased glycolysis, after compared to before the exercise training period in RPF only. Baseline endothelial G protein-coupled oestrogen receptor (P = 0.028) and muscle capillarisation (P = 0.028) was lower in LPF than in RPF. Muscle vascular endothelial growth factor protein was higher (32%; P = 0.002) following exercise training in LPF only. Exercise training did not influence endothelial cell proliferation or skeletal muscle capillarisation in either group, but the CD31 level in the muscle tissue, indicating endothelial cell content, was higher (>50%; P < 0.05) in both groups. In conclusion, 8 weeks of intense aerobic exercise training reduces ROS formation and enhances glycolysis in microvascular endothelial cells from RPF but does not induce skeletal muscle angiogenesis. KEY POINTS: Late postmenopausal females have been reported to achieve limited vascular adaptations to exercise training. There is a paucity of data on the effect of exercise training on isolated skeletal muscle microvascular endothelial cells (MMECs). In this study the formation of reactive oxygen species in MMECs was reduced and glycolysis increased after 8 weeks of aerobic exercise training in recent but not late postmenopausal females. Late postmenopausal females had lower levels of G protein-coupled oestrogen receptor in MMECs and lower skeletal muscle capillary density at baseline. Eight weeks of intense exercise training altered MMEC properties but did not induce skeletal muscle angiogenesis in postmenopausal females.

Myocardial proteome changes in aortic stenosis rats subjected to long-term aerobic exercise.

The effects of exercise training (ET) on the heart of aortic stenosis (AS) rats are controversial and the mechanisms involved in alterations induced by ET have been poorly clarified. In this study, we analyzed the myocardial proteome to identify proteins modulated by moderate-intensity aerobic ET in rats with chronic supravalvular AS. Wistar rats were divided into four groups: sedentary control (C-Sed), exercised control (C-Ex), sedentary aortic stenosis (AS-Sed), and exercised AS (AS-Ex). ET consisted of five treadmill running sessions per week for 16 weeks. Statistical analysis was performed by ANOVA or Kruskal-Wallis and Goodman tests. Results were discussed at a significance level of 5%. At the end of the experiment, AS-Ex rats had higher functional capacity, lower blood lactate concentration, and better cardiac structural and left ventricular (LV) functional parameters than the AS-Sed. Myocardial proteome analysis showed that AS-Sed had higher relative protein abundance related to the glycolytic pathway, oxidative stress, and inflammation, and lower relative protein abundance related to beta-oxidation than C-Sed. AS-Ex had higher abundance of one protein related to mitochondrial biogenesis and lower relative protein abundance associated with oxidative stress and inflammation than AS-Sed. Proteomic data were validated for proteins related to lipid and glycolytic metabolism. Chronic pressure overload changes the abundance of myocardial proteins that are mainly involved in lipid and glycolytic energy metabolism in rats. Moderate-intensity aerobic training attenuates changes in proteins related to oxidative stress and inflammation and increases the COX4I1 protein, related to mitochondrial biogenesis. Protein changes are combined with improved functional capacity, cardiac remodeling, and LV function in AS rats.

Effect of Exercise Training on Prognosis in Community-acquired Pneumonia: A Randomized Controlled Trial.

OBJECTIVE: To investigate the effect of standard care (SoC) combined with supervised in-bed cycling (Bed-Cycle) or booklet exercises (Book-Exe) versus SoC in community-acquired pneumonia (CAP). METHODS: In this randomized controlled trial, 186 patients with CAP were assigned to SoC (n = 62), Bed-Cycle (n = 61), or Book-Exe (n = 63). Primary outcome length of stay (LOS) was analyzed with analysis of covariance. Secondary outcomes, 90-day readmission, and 180-day mortality were analyzed with Cox proportional hazard regression and readmission days with negative-binominal regression. RESULTS: LOS was -2% (95% CI: -24 to 25) and -1% (95% CI: -22 to 27) for Bed-Cycle and Book-Exe, compared with SoC. Ninety-day readmission was 35.6% for SoC, 27.6% for Bed-Cycle, and 21.3% for Book-Exe. Adjusted hazard ratio (aHR) for 90-day readmission was 0.63 (95% CI: .33-1.21) and 0.54 (95% CI: .27-1.08) for Bed-Cycle and Book-Exe compared with SoC. aHR for 90-day readmission for combined exercise was 0.59 (95% CI: .33-1.03) compared with SoC. aHR for 180-day mortality was 0.84 (95% CI: .27-2.60) and 0.82 (95% CI: .26-2.55) for Bed-Cycle and Book-Exe compared with SoC. Number of readmission days was 226 for SoC, 161 for Bed-Cycle, and 179 for Book-Exe. Incidence rate ratio for readmission days was 0.73 (95% CI: .48-1.10) and 0.77 (95% CI: .51-1.15) for Bed-Cycle and Book-Exe compared with SoC. CONCLUSIONS: Although supervised exercise training during admission with CAP did not reduce LOS or mortality, this trial suggests its potential to reduce readmission risk and number of readmission days. CLINICAL TRIALS REGISTRATION: NCT04094636.

Exercise Training and Spexin Ameliorate Thyroid Changes in Obese Type 2-Diabetic Rats: The Possible Interlaying Mechanisms.

Thyroid dysfunction and diabetes mellitus are prevalent endocrine disorders that often coexist and influence each other. The role of spexin (SPX) in diabetes and obesity is well-documented, but its connection to thyroid function is less understood. This study investigates the influence of exercise (EX) and SPX on thyroid hypofunction in obese type 2 diabetic rats. Rats were divided into normal control, obese diabetic sedentary, obese diabetic EX, and obese diabetic SPX groups, with subdivisions for M871, and HT-2157 treatment in the later 2 groups. High-fat diet together with streptozotocin injection induced obesity and diabetes. The EX-group underwent swimming, while the SPX-group received SPX injections for eight weeks. Results showed significant improvements in thyroid function, metabolic, oxidative, and inflammatory states with EX and SPX-treatment. The study also explored the involvement of galanin receptor isoforms (GALR) 2/3 in SPX effects on thyroid function. Blocking GALR2/3 receptors partially attenuated the beneficial effects, indicating their interaction. These findings underscore the importance of EX and SPX in modulating thyroid function in obesity and diabetes. Comprehending this interplay could enable the development of new treatment approaches for thyroid disorders associated with obese type 2 diabetes. Additional research is necessary to clarify the exact mechanisms connecting SPX, EX activity, and thyroid function.

Comparative effects of 8-week combined resistance exercise training and alternate-day calorie restriction on soluble epidermal growth factor receptor (sEGFR) and adipsin in obese men.

This study investigated the combined effects of resistance exercise training (RET) and alternate-day calorie restriction (ADCR) on body composition, insulin resistance (IR), insulin resistance-related biomarkers (adipokine adipsin and hepatokine soluble EFGR), and weight loss in obese men. The findings revealed that RET + ADCR induced the greatest reductions in body weight, body fat percentage, and waist-to-hip ratio (WHR) compared to RET and ADCR alone (p < 0.05). Additionally, RET + ADCR resulted in the most significant improvements in IR, as measured by HOMA-IR, and in circulating levels of adipsin and soluble EFGR (p < 0.05). These findings suggest that combining RET and ADCR may be a more effective strategy for improving metabolic health, including body composition, IR, and metabolic tissues' functions, in obese men than either intervention alone.

Aerobic exercise-induced HIF-1α upregulation in heart failure: exploring potential impacts on MCT1 and MPC1 regulation.

BACKGROUND: The terminal stage of ischemic heart disease develops into heart failure (HF), which is characterized by hypoxia and metabolic disturbances in cardiomyocytes. The hypoxic failing heart triggers hypoxia-inducible factor-1α (HIF-1α) actions in the cells sensitized to hypoxia and induces metabolic adaptation by accumulating HIF-1α. Furthermore, soluble monocarboxylic acid transporter protein 1 (MCT1) and mitochondrial pyruvate carrier 1 (MPC1), as key nodes of metabolic adaptation, affect metabolic homeostasis in the failing rat heart. Aerobic exercise training has been reported to retard the progression of HF due to enhancing HIF-1α levels as well as MCT1 expressions, whereas the effects of exercise on MCT1 and MPC1 in HF (hypoxia) remain elusive. This research aimed to investigate the action of exercise associated with MCT1 and MPC1 on HF under hypoxia. METHODS: The experimental rat models are composed of four study groups: sham stented (SHAM), HF sedentary (HF), HF short-term exercise trained (HF-E1), HF long-term exercise trained (HF-E2). HF was initiated via left anterior descending coronary artery ligation, the effects of exercise on the progression of HF were analyzed by ventricular ultrasound (ejection fraction, fractional shortening) and histological staining. The regulatory effects of HIF-1α on cell growth, MCT1 and MPC1 protein expression in hypoxic H9c2 cells were evaluated by HIF-1α activatort/inhibitor treatment and plasmid transfection. RESULTS: Our results indicate the presence of severe pathological remodelling (as evidenced by deep myocardial fibrosis, increased infarct size and abnormal hypertrophy of the myocardium, etc.) and reduced cardiac function in the failing hearts of rats in the HF group compared to the SHAM group. Treadmill exercise training ameliorated myocardial infarction (MI)-induced cardiac pathological remodelling and enhanced cardiac function in HF exercise group rats, and significantly increased the expression of HIF-1α (p < 0.05), MCT1 (p < 0.01) and MPC1 (p < 0.05) proteins compared to HF group rats. Moreover, pharmacological inhibition of HIF-1α in hypoxic H9c2 cells dramatically downregulated MCT1 and MPC1 protein expression. This phenomenon is consistent with knockdown of HIF-1α at the gene level. CONCLUSION: The findings propose that long-term aerobic exercise training, as a non- pharmacological treatment, is efficient enough to debilitate the disease process, improve the pathological phenotype, and reinstate cardiac function in HF rats. This benefit is most likely due to activation of myocardial HIF-1α and upregulation of MCT1 and MPC1.

Cardiac functional adaptation to resistance and endurance exercise training: a randomized crossover study.

Few training studies have assessed the impact of different modes of exercise on changes in cardiac function. This study investigated changes in left ventricular (LV) systolic and diastolic function following endurance (END) and resistance (RES) training in healthy participants. Sixty-four individuals participated in a randomized crossover design trial, involving 12 wk of END and RES training, separated by a 12-wk washout. Echocardiograms assessed systolic function [ejection fraction (EF) and global longitudinal strain (GLS)], diastolic function [mitral valve early velocity (E), tissue Doppler velocity (e'), their ratio (E/e')], and left atrial volume indexed to body surface area (LA ESVi). LV mass (LVM) increased with both RES (Δ5.3 ± 11.9, P = 0.001) and END (Δ7.5 ± 13.9, P < 0.001). Once adjusted for lean body mass (LVMi), changes remained significant following END. E/e' improved following END (Δ-0.35 ± 0.98, P = 0.011) not RES (Δ0.35 ± 1.11, P =0.157; P = 0.001 between modes). LA ESVi increased with END (Δ2.0 ± 6.1, P = 0.019) but not RES (Δ1.7 ± 5.7, P = 0.113). EF and GLS were not impacted significantly by either mode of training. Adaptation in LVM and LA volumes, as well as diastolic function, was exercise mode specific. Twelve weeks of intensive END increased LVM, LA volumes, and increased diastolic function. Following RES, LVM increased, although this was attenuated after accounting for changes in lean body mass. There were no changes in systolic function following either mode of exercise training.NEW & NOTEWORTHY Different types of exercise training induce distinct physiological adaptations however few exercise training studies have assessed the impact of different modes of exercise on cardiac function. This study investigated changes in left ventricular systolic and diastolic function following exercise training. Participants completed both endurance and resistance training separated by a 12-wk washout period so each participant is their own control. We present adaptations in cardiac structure and diastolic function are exercise mode specific.

MicroRNAs regulating signaling pathways in cardiac fibrosis: potential role of the exercise training.

Cardiovascular and metabolic diseases such as hypertension, type 2 diabetes, and obesity develop long-term fibrotic processes in the heart, promoting pathological cardiac remodeling, including after myocardial infarction, reparative fibrotic processes also occur. These processes are regulated by many intracellular signaling pathways that have not yet been completely elucidated, including those associated with microRNA (miRNA) expression. miRNAs are small RNA transcripts (18-25 nucleotides in length) that act as posttranscriptionally regulators of gene expression, inhibiting or degrading one or more target messenger RNAs (mRNAs), and proven to be involved in many biological processes such as cell cycle, differentiation, proliferation, migration, and apoptosis, directly affecting the pathophysiology of several diseases, including cardiac fibrosis. Exercise training can modulate the expression of miRNAs and it is known to be beneficial in various cardiovascular diseases, attenuating cardiac fibrosis processes. However, the signaling pathways modulated by the exercise associated with miRNAs in cardiac fibrosis were not fully understood. Thus, this review aims to analyze the expression of miRNAs that modulate signaling pathways in cardiac fibrosis processes that can be regulated by exercise training.

Aerobic exercise training combined with local strength exercise restores muscle blood flow and maximal aerobic capacity in long-term Hodgkin lymphoma survivors.

It is unclear whether muscle blood flow (MBF) is altered in long-term Hodgkin lymphoma (HL) survivors. We tested the hypothesis that 1) MBF response during mental stress (MS) is impaired in long-term HL survivors and 2) aerobic exercise training combined with local strength exercise (ET) restores MBF responses during MS in these survivors. Eighteen 5-year HL survivors and 10 aged-paired healthy subjects (HC) were studied. Twenty HL survivors were randomly divided into two groups: exercise-trained (HLT, n = 10) and untrained (HLUT, n = 10). Maximal aerobic capacity was evaluated by a cardiopulmonary exercise test and forearm blood flow (FBF) by venous occlusion plethysmography. MS was elicited by Stroop color and word test. ET was conducted for 4 mo, 3/wk for 60 min each session. The aerobic exercise intensity corresponded to anaerobic threshold up to 10% below the respiratory compensation point. The strength exercises consisted of two to three sets of chest press, pulley and squat exercises, 12-15 repetitions each exercise at 30-50% of the maximal voluntary contraction. Baseline was similar in HL survivors and HC, except peak oxygen consumption (peak V̇o2, P = 0.013) and FBF (P = 0.006) that were lower in the HL survivors. FBF responses during MS were lower in HL survivors (P < 0.001). ET increased peak V̇o2 (11.59 ± 3.07%, P = 0.002) and FBF at rest (33.74 ± 5.13%, P < 0.001) and during MS (24 ± 5.31%, P = 0.001). Further analysis showed correlation between the changes in peak V̇o2 and the changes in FBF during MS (r = 0.711, P = 0.001). In conclusion, long-term HL survivors have impaired MBF responses during MS. ET restores MBF responses during MS.NEW & NOTEWORTHY Long-term Hodgkin lymphoma (HL) survivors have impaired muscle blood flow responses during mental stress and decreased maximal aerobic capacity. Supervised aerobic exercise training combined with local strength exercises restores muscle blood flow responses during mental stress and maximal aerobic capacity in these survivors. These findings provide evidence of safety and effectiveness of exercise training in HL survivors. Moreover, they highlight the importance of exercise training in the treatment of this set of patients.

Effect of Preoperative Home-Based Exercise Training on Quality of Life After Lung Cancer Surgery: A Multicenter Randomized Controlled Trial.

BACKGROUND: Preoperative exercise training is recommended for improvement of clinical outcomes after lung cancer (LC) surgery. However, its effectiveness in preventing postoperative decline in quality of life (QoL) remains unknown. This study investigated the effect of preoperative home-based exercise training (PHET) on QoL after LC surgery. METHODS: Patients awaiting LC resection were randomized to PHET or a control group (CG). The PHET program combined aerobic and resistance exercise, with weekly telephone supervision. Primary outcome was QoL-assessed with the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire C30 (QLQ-C30) at baseline, before surgery, and 1 month after surgery. The secondary outcomes were hospital length of stay and physical performance. The main analysis included a factorial repeated-measures analysis of variance. Additionally, the proportion of patients experiencing clinical deterioration from baseline to post-surgery was assessed. RESULTS: The study included 41 patients (68.1 ± 9.3 years; 68.3% male) in the intention-to-treat analysis (20 PHET patients, 21 CG patients). A significant group × time interaction was observed for global QoL (p = 0.004). Between-group differences in global QoL were statistically and clinically significant before surgery (mean difference [MD], 13.5 points; 95% confidence interval [CI], 2.4-24.6; p = 0.019) and after surgery (MD, 12.4 points; 95% CI, 1.3-23.4; p = 0.029), favoring PHET. Clinical deterioration of global QoL was reported by 71.4% of the CG patients compared with 30 % of the PHET patients (p = 0.003). Between-group differences in favor of PHET were found in pain and appetite loss as well as in physical, emotional and role functions after surgery (p < 0.05). Compared with CG, PHET was superior in improving preoperative five-times sit-to-stand and postoperative exercise capacity (p < 0.05). No between-group differences in other secondary outcomes were observed. CONCLUSION: The study showed that PHET can effectively prevent the decline in QoL after LC surgery.

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

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

Exercise intolerance in heart failure with preserved ejection fraction: Causes, consequences and the journey towards a cure.

Heart failure with preserved ejection fraction (HFpEF) accounts for over 50% of all heart failure cases nationwide and continues to rise in its prevalence. The complex, multi-organ involvement of the HFpEF clinical syndrome requires clinicians and investigators to adopt an integrative approach that considers the contribution of both cardiac and non-cardiac function to HFpEF pathophysiology. Thus, this symposium review outlines the key points from presentations covering the contributions of disease-related changes in cardiac function, arterial stiffness, peripheral vascular function, and oxygen delivery and utilization to exercise tolerance in patients with HFpEF. While many aspects of HFpEF pathophysiology remain poorly understood, there is accumulating evidence for a decline in vascular health in this patient group that may be remediable through pharmacological and lifestyle interventions and could improve outcomes and clinical status in this ever-growing patient population.