High-Intensity Interval Training Is Associated With Improved 10-Year Survival by Mediating Left Ventricular Remodeling in Patients With Heart Failure With Reduced and Mid-Range Ejection Fraction.

BACKGROUND: This study aimed to assess the left ventricular (LV) remodeling response and long-term survival after high-intensity interval training (HIIT) in patients with various heart failure (HF) phenotypes during a 10-year longitudinal follow-up. METHODS AND RESULTS: Among 214 patients with HF receiving guideline-directed medical therapy, those who underwent an additional 36 sessions of aerobic exercise at alternating intensities of 80% and 40% peak oxygen consumption (V̇$$ \dot{\mathrm{V}} $$O2peak) were considered HIIT participants (n=96). Patients who did not undergo HIIT were considered participants receiving guideline-directed medical therapy (n=118). Participants with LV ejection fraction (EF) <40%, ≥40% and <50%, and ≥50% were considered to have HF with reduced EF, HF with mid-range EF, and HF with preserved EF, respectively. V̇$$ \dot{\mathrm{V}} $$O2peak, serial LV geometry, and time to death were recorded. In all included participants, 10-year survival was better (P=0.015) for participants who underwent HIIT (80.3%) than for participants receiving guideline-directed medical therapy (68.6%). An increased V̇$$ \dot{\mathrm{V}} $$O2peak, decreased minute ventilation carbon dioxide production slope, and reduced LV end-diastolic diameter were protective factors against all-cause mortality. Regarding 138 patients with HF with reduced EF (P=0.044) and 36 patients with HF with mid-range EF (P=0.036), 10-year survival was better for participants who underwent HIIT than for participants on guideline-directed medical therapy. Causal mediation analysis showed a significant mediation path for LV end-diastolic diameter on the association between HIIT and 10-year mortality in all included patients with HF (P<0.001) and those with LV ejection fraction <50% (P=0.006). HIIT also had a significant direct association with 10-year mortality in patients with HF with LV ejection fraction <50% (P=0.027) but not in those with LV ejection fraction ≥50% (n=40). CONCLUSIONS: Reversal of LV remodeling after HIIT could be a significant mediating factor for 10-year survival in patients with HF with reduced EF and those with HF with mid-range EF.

Interval aerobic/resistance exercise training depresses adrenergic-induced apoptosis of lymphocytes in sedentary males.

PURPOSE: Adrenergic stimulation affects lymphocyte autophagy and apoptosis by activating ß1-adrenergic receptor (ß1-AR) and G protein-coupled receptor kinase 2 (GRK-2) downstream signaling. This study investigated how combined aerobic and resistance exercise training on the interval or continuous pattern influences aerobic/muscular fitness and ß1-AR/GRK-2 signaling, and corresponding apoptosis/autophagy of lymphocytes in sedentary males. METHODS: Thirty-four sedentary males were randomized into interval training (IT, age = 22.5 ± 0.6 years, fitness level = 47.5 ± 0.9 mL/min/kg, body mass index (BMI) = 22.4 ± 0.4 kg/m2, n = 17) and continuous training (CT, age = 21.6 ± 0.4 years, fitness level = 45.2 ± 1.0 mL/min/kg, BMI = 22.2 ± 0.3 kg/m2, n = 17) groups. These subjects performed IT (bicycle exercise at alternating 40% and 80%VO2 reserve (VO2R) and isokinetic exercise at alternating 60°/s and 180°/s) or CT (bicycle exercise at continuously 60%VO2R and isokinetic exercise at continuously 120°/s) for 30 min/day, 5 days/week for 6 weeks. Aerobic capacity and muscular strength/endurance were determined by the graded exercise test (GXT) and isokinetic strength test, respectively. Blood lymphocyte autophagy/apoptosis and ß1-AR/GRK-2 signaling were analyzed using flow cytometry. RESULTS: Both IT and CT groups increased isokinetic strengths at various angular velocities, whereas only IT significantly enhanced muscle endurance, indicated by lowered fatigue index from 47.0 ± 1.3% to 41.8 ± 1.6% (P < 0.05). Moreover, the IT group (143 ± 7%) revealed a higher improvement in VO2peak than CT group (132 ± 6%) (P < 0.05). Acute GXT augmented (i) GRK-2 and protein kinase A expressions, (ii) LAMP-2 upregulation and acridine orange staining, (iii) mitochondrial transmembrane potential diminishing, caspase-3 activation, and phosphatidylserine (PS) exposure caused by epinephrine in blood lymphocytes. However, the degree of epinephrine-induced lymphocyte PS exposure potentiated by GXT was suppressed from 65.2 ± 5.2% to 47.4 ± 6.5% following 6 weeks of the IT (P < 0.05). CONCLUSION: The IT may be considered more beneficial than CT in terms of improving aerobic/muscular fitness and simultaneously ameliorating apoptosis of blood lymphocyte evoked by intense exercise or adrenergic stimulation in sedentary males.

Hypermethylation of ACADVL is involved in the high-intensity interval training-associated reduction of cardiac fibrosis in heart failure patients.

BACKGROUND: Emerging evidence suggests that DNA methylation can be affected by physical activities and is associated with cardiac fibrosis. This translational research examined the implications of DNA methylation associated with the high-intensity interval training (HIIT) effects on cardiac fibrosis in patients with heart failure (HF). METHODS: Twelve HF patients were included and received cardiovascular magnetic resonance imaging with late gadolinium enhancement for cardiac fibrosis severity and a cardiopulmonary exercise test for peak oxygen consumption ([Formula: see text]O2peak). Afterwards, they underwent 36 sessions of HIIT at alternating 80% and 40% of [Formula: see text]O2peak for 30 min per session in 3-4 months. Human serum from 11 participants, as a means to link cell biology to clinical presentations, was used to investigate the exercise effects on cardiac fibrosis. Primary human cardiac fibroblasts (HCFs) were incubated in patient serum, and analyses of cell behaviour, proteomics (n = 6) and DNA methylation profiling (n = 3) were performed. All measurements were conducted after completing HIIT. RESULTS: A significant increase (p = 0.009) in [Formula: see text]O2peak (pre- vs. post-HIIT = 19.0 ± 1.1 O2 ml/kg/min vs. 21.8 ± 1.1 O2 ml/kg/min) was observed after HIIT. The exercise strategy resulted in a significant decrease in left ventricle (LV) volume by 15% to 40% (p < 0.05) and a significant increase in LV ejection fraction by approximately 30% (p = 0.010). LV myocardial fibrosis significantly decreased from 30.9 ± 1.2% to 27.2 ± 0.8% (p = 0.013) and from 33.4 ± 1.6% to 30.1 ± 1.6% (p = 0.021) in the middle and apical LV myocardium after HIIT, respectively. The mean single-cell migration speed was significantly (p = 0.044) greater for HCFs treated with patient serum before (2.15 ± 0.17 µm/min) than after (1.11 ± 0.12 µm/min) HIIT. Forty-three of 1222 identified proteins were significantly involved in HIIT-induced altered HCF activities. There was significant (p = 0.044) hypermethylation of the acyl-CoA dehydrogenase very long chain (ACADVL) gene with a 4.474-fold increase after HIIT, which could activate downstream caspase-mediated actin disassembly and the cell death pathway. CONCLUSIONS: Human investigation has shown that HIIT is associated with reduced cardiac fibrosis in HF patients. Hypermethylation of ACADVL after HIIT may contribute to impeding HCF activities. This exercise-associated epigenetic reprogramming may contribute to reduce cardiac fibrosis and promote cardiorespiratory fitness in HF patients. TRIAL REGISTRATION: NCT04038723. Registered 31 July 2019, https://clinicaltrials.gov/ct2/show/NCT04038723 .

Trajectories of social support are associated with health outcomes and depressive symptoms among older Taiwanese adults with diabetes following hip-fracture surgery.

OBJECTIVE: This study examined trajectories of social support and their relationships with health outcomes over 2 years post hip-fracture surgery for older adults with diabetes mellitus (DM). METHODS: This was a secondary analysis of data derived from a clinical trial, which included 158 hip fractured older adults with DM who had completed the Medical Outcomes Study Social Support Survey at 1-, 12-, 18-, and 24-months following hospital discharge. Health outcomes for self-care, physical and nutritional status, mental health, and depression were assessed at 3-month intervals up to 24-months after hospital discharge. Trajectories of social support were derived with latent class analysis while hierarchical linear models were employed to assess the associations of social-support trajectory with health outcomes. RESULTS: Four social-support trajectories were derived for persons with DM following hip-fracture surgery: poor and declining (n = 18, 11.4%), moderate and stable (n = 29, 18.4%), high but declining (n = 34, 21.5%), and high and stable (n = 77, 48.7%). Relative to those in the poor and declining group, participants in the high and stable trajectory group performed better in Activities of Daily Living and quadriceps muscle power, had better mental Health-Related Quality of Life and nutritional status, and had fewer depressive symptoms. These differences persisted over the 2 years following hospital discharge. CONCLUSIONS: These results suggest social support for persons with DM should be continually assessed following hip-fracture surgery.

The Effects of Exercise Training on Mitochondrial Function in Cardiovascular Diseases: A Systematic Review and Meta-Analysis.

Mitochondria dysfunction is implicated in the pathogenesis of cardiovascular diseases (CVD). Exercise training is potentially an effective non-pharmacological strategy to restore mitochondrial health in CVD. However, how exercise modifies mitochondrial functionality is inconclusive. We conducted a systematic review using the PubMed; Scopus and Web of Science databases to investigate the effect of exercise training on mitochondrial function in CVD patients. Search terms included "mitochondria", "exercise", "aerobic capacity", and "cardiovascular disease" in varied combination. The search yielded 821 records for abstract screening, of which 20 articles met the inclusion criteria. We summarized the effect of exercise training on mitochondrial morphology, biogenesis, dynamics, oxidative capacity, antioxidant capacity, and quality. Amongst these parameters, only oxidative capacity was suitable for a meta-analysis, which demonstrated a significant effect size of exercise in improving mitochondrial oxidative capacity in CVD patients (SMD = 4.78; CI = 2.99 to 6.57; p < 0.01), but with high heterogeneity among the studies (I2 = 75%, p = 0.003). Notably, aerobic exercise enhanced succinate-involved oxidative phosphorylation. The majority of the results suggested that exercise improves morphology and biogenesis, whereas findings on dynamic, antioxidant capacity, and quality, were inadequate or inconclusive. A further randomized controlled trial is clearly required to explain how exercise modifies the pathway of mitochondrial quantity and quality in CVD patients.

Role of helmet ventilation during the 2019 coronavirus disease pandemic.

Coronavirus disease 2019 (COVID-19) has been declared a pandemic by the World Health Organization; it has affected millions of people and caused hundreds of thousands of deaths. Patients with COVID-19 pneumonia may develop acute hypoxia respiratory failure and require noninvasive respiratory support or invasive respiratory management. Healthcare workers have a high risk of contracting COVID-19 while fitting respiratory devices. Recently, European experts have suggested that the use of helmet continuous positive airway pressure should be the first choice for acute hypoxia respiratory failure caused by COVID-19 because it reduces the spread of the virus in the ambient air. By contrast, in the United States, helmets were restricted for respiratory care before the COVID-19 pandemic until the Food and Drug Administration provided the 'Umbrella Emergency Use Authorization for Ventilators and Ventilator Accessories'. This narrative review provides an evidence-based overview of the use of helmet ventilation for patients with respiratory failure.

A pilot crossover trial assessing the exercise performance patients chronic obstructive pulmonary disease.

Noninvasive ventilation improves exercise performance in patients with chronic obstructive pulmonary disease (COPD). However, the effect of helmet ventilation (HV) on the short-term self-paced exercise performance of patients with COPD remains unclear. This study investigated the use of HV during a 6 min walk test (6MWT) and analyzed its short-term cardiopulmonary outcomes in patients with stable COPD. A single-site crossover trial was conducted in a pulmonary rehabilitation outpatient department. A total of 20 stable patients with COPD without disability were enrolled. The participants performed 6MWTs with and without HV on two consecutive days. The outcome measures were the distance walked in the 6MWT and the physiological and cardiopulmonary parameters. The mean difference in meters walked between the HV-aided and unaided walk tests was 15.4 ± 37.2 (95% confidence interval: - 2.03 to 32.8 m; p = .145). During the 6MWT, the peak heart rate was significantly higher when walking was aided by HV than when it was unaided (p < .001). The energy expenditure index, walking speed, oxygen saturation nadir, and hemodynamic parameters were comparable. Although carbon dioxide levels inside the helmet increased after the walk test, the participants' transcutaneous carbon dioxide measurements remained unchanged. HV did not improve the short-term self-paced exercise performance in patients with stable mild-to-moderate COPD. Further research should focus on noninvasive ventilation delivered via helmets in exercise training to determine the setting strategy, breathing circuit configuration, and effects of regular exercise.ClinicalTrial.gov: NCT04156724; IRB number: C108032.

Stepper-Based Training Improves Monocyte-Platelet Aggregation and Thrombin Generation in Nonambulatory Hemiplegic Patients.

PURPOSE: Nonambulatory stroke patients are extremely sedentary, but most available data concerning exercise training in stroke patients are related to ambulatory patients. This study aimed to investigate the efficacy of stepper-based exercise training on cardiopulmonary fitness, monocyte subtypes, and associated monocyte-platelet aggregates (MPA) and thrombin generation (TrG) in nonambulatory hemiplegic patients with ischemic stroke. METHOD: Thirty-eight patients were randomized into exercise training (ET, n = 20) and usual care (UC, n = 18) groups. The ET underwent supervised exercise training (60% peak work rate) using a recumbent stepper for two to four sessions per week and 36 sessions in total. In addition, 12 healthy participants were enrolled as healthy controls. Monocyte characteristics, MPA, and plasma TrG kinetics were determined before and after intervention by flow cytometry and calibrated automated thrombogram® (CAT). RESULTS: Seventeen and 15 patients completed the protocol in the ET and UC groups. Peak V̇O2 improved in ET (15.7 ± 4.8 vs 18.9 ± 5.3 mL·min-1·kg-1, +20%), so did the phase angle of the hemiplegic limbs. The counts of total MPA and MPA associated with three monocyte subtypes, alongside CD42b expression all declined in ET with subtypes 2 and 1 being the most prominent. Macrophage inflammatory protein 1ß (MIP-1 ß) level also declined. The TrG kinetics was attenuated after ET by delaying initiation and reducing the rising slope and peak of thrombin production. In UC, no difference was revealed in the pre-post comparison. CONCLUSIONS: Stepper-based ET is feasible in nonambulatory hemiplegic patients and is effective in improving aerobic fitness. Moreover, it decreases heteroaggregation of monocytes with platelets, especially in monocyte subtypes 2 and 1. Thrombin generation was also attenuated. Hence, stepper-based ET may be incorporated in the rehabilitation of nonambulatory hemiplegic patients.

Exercise Training Improves Mitochondrial Bioenergetics of Natural Killer Cells.

INTRODUCTION: Mitochondrial bioenergetics is critical for immune function in natural killer (NK) cell. Physical exercise modulates NK cell functionality, depending on the intensity and type of exercise. This study elucidates how interval and continuous exercise regimens affect the phenotypes and mitochondrial bioenergetics of NK cells. METHODS: Sixty healthy sedentary males were randomly assigned to engage in either high-intensity interval training (HIIT, 3-min intervals at 80% and 40% maximal O2, n = 20; age, 22.2 yr; body mass index [BMI], 24.3 kg·m-2) or moderate-intensity continuous training (MICT, sustained 60% maximal O2, n = 20; age, 22.3 yr; BMI, 23.3 kg·m-2) for 30 min·d-1, 5 d·wk-1 for 6 wk or were assigned to a control group that did not receive exercise intervention (n = 20; age, 22.6 yr; BMI, 24.0 kg·m-2). Natural killer cell phenotypes, granule proteins, and mitochondrial oxidative stress/oxidative phosphorylation after graded exercise test (GXT) were measured before and after the various interventions. RESULTS: Before the intervention, the GXT increased the mobilization of CD57+NK cells into the blood and elevated mitochondrial matrix oxidant burden (MOB) in NK cells, Following the 6 wk of interventions, both HIIT and MICT (i) diminished mobilization of CD57+NK cells into the blood and depressed mitochondrial MOB level in NK cells immediately after GXT, (ii) increased mitochondrial membrane potential and cellular perforin and granzyme B levels in NK cells, and (iii) enhanced the maximal and reserve O2 consumption rates and heightened bioenergetic health index in NK cells. In addition, HIIT increased maximal work rate than those of MICT. CONCLUSIONS: Either HIIT or MICT increases the expressions of cytotoxic granule proteins and depresses mitochondrial MOB elevated by GXT, along with improving mitochondrial bioenergetic functionality in NK cells. Moreover, HIIT is superior to MICT in improving aerobic capacity.

Effects of high-flow nasal cannula with oxygen on self-paced exercise performance in COPD: A randomized cross-over trial.

INTRODUCTION: Studies have demonstrated that noninvasive ventilation improves exercise intolerance in patients with chronic obstructive pulmonary disease (COPD). The role of heated humidified high-flow nasal cannula (HFNC) therapy in patients with COPD on self-paced exercise performance remains unclear. Therefore, the purpose of the present study was to determine whether HFNC-aided supplemental oxygen during a 6-minute walk test (6MWT) would change self-paced exercise performance and cardiopulmonary outcomes in patients with stable COPD. METHODS: A single-site, cross-over trial was conducted in a pulmonary rehabilitation outpatient department. This study enrolled 30 stable COPD patients without disability. The participants with and without HFNC performed 6MWTs on 2 consecutive days. Outcomes were the distance walked in the 6MWT, physiological, and cardiopulmonary parameters. RESULTS: Those performing HFNC-aided walking exhibited a longer walking distance than those performing unaided walking. The mean difference in meters walked between the HFNC-aided and unaided walking scenarios was 27.3 ±â€Š35.6 m (95% CI: 14.4-40.5 m). The energy expenditure index was significantly lower when walking was aided by HHHNFC rather than unaided (median: 1.21 beats/m walked vs median: 1.37 beats/m walked, P < .001). However, there were no differences in transcutaneous carbon dioxide tension between HHHNFC and non-HHHNFC patients. CONCLUSION: Walking distance and arterial oxygen saturation improved in stable COPD patients receiving HFNC with additional oxygen support. However, HFNC did not affect transcutaneous carbon dioxide tension and the self-reported dyspnea score during the walking test. The present study demonstrated the feasibility and safety of using HFNC in self-paced exercise. TRIAL REGISTRATION: NCT03863821.

Different Involvement of Band 3 in Red Cell Deformability and Osmotic Fragility-A Comparative GP.Mur Erythrocyte Study.

GP.Mur is a clinically important red blood cell (RBC) phenotype in Southeast Asia. The molecular entity of GP.Mur is glycophorin B-A-B hybrid protein that promotes band 3 expression and band 3-AQP1 interaction, and alters the organization of band 3 complexes with Rh/RhAG complexes. GP.Mur+ RBCs are more resistant to osmotic stress. To explore whether GP.Mur+ RBCs could be structurally more resilient, we compared deformability and osmotic fragility of fresh RBCs from 145 adults without major illness (47% GP.Mur). We also evaluated potential impacts of cellular and lipid factors on RBC deformability and osmotic resistivity. Contrary to our anticipation, these two physical properties were independent from each other based on multivariate regression analyses. GP.Mur+ RBCs were less deformable than non-GP.Mur RBCs. We also unexpectedly found 25% microcytosis in GP.Mur+ female subjects (10/40). Both microcytosis and membrane cholesterol reduced deformability, but the latter was only observed in non-GP.Mur and not GP.Mur+ normocytes. The osmotic fragility of erythrocytes was not affected by microcytosis; instead, larger mean corpuscular volume (MCV) increased the chances of hypotonic burst. From comparison with GP.Mur+ RBCs, higher band 3 expression strengthened the structure of RBC membrane and submembranous cytoskeletal networks and thereby reduced cell deformability; stronger band 3-AQP1 interaction additionally supported osmotic resistance. Thus, red cell deformability and osmotic resistivity involve distinct structural-functional roles of band 3.

The validation of oxygen uptake efficiency slope in patients with stroke.

ABSTRACT: To evaluate the real aerobic capacity is difficult due to impaired limbs function in stroke patients. Oxygen uptake efficiency slope (OUES) could represent the aerobic capacity in submaximal exercise test. Hence, we designed this observational study to investigate the application of the OUES for evaluating aerobic capacity in these patients.Thirty-seven stroke patients were classified into 2 groups according to their Brunnstrom stage of affected lower limbs. Patients underwent cardiopulmonary exercise testing to assess cardiorespiratory fitness. Minute ventilation and oxygen consumption were measured, and OUES was calculated, compared with healthy reference values, and correlated with the peak oxygen consumption. The predictive validity of submaximal OUES was derived.Study participants' OUES (median 566.2 [IQR, 470.0-711.6]) was 60% of healthy reference values and correlated positively with the peak oxygen consumption (r = 0.835) (P < .01). The predictive validity of oxygen uptake efficiency slope at 50% of maximal exercise duration (OUES50) and oxygen uptake efficiency slope at 75% of maximal exercise duration (OUES75) for oxygen uptake efficiency slope at 100% of maximal exercise duration (OUES100) was 0.877 and 0.973, respectively (P < .01). The OUES50, OUES75, and OUES100 groups were not significantly different; agreement of submaximal and maximal OUES values was strong.OUES is a valuable submaximal index for evaluating cardiorespiratory fitness in stroke patients. Moderate-to-high concurrent validity of this parameter with peak oxygen consumption and the high predictive validity of OUES50 and OUES75 for OUES100 suggest maximal exercise testing in stroke patients who cannot reach maximal exercise is unnecessary.

Low-Frequency Vibration Facilitates Post-Exercise Cardiovascular Autonomic Recovery.

It is important to use short breaks to accelerate post-exercise recovery in sports. Previous studies have revealed that vibration can reduce post-exercise muscle soreness. However, there is still high heterogeneity in the effects of vibration on cardiovascular autonomic activities, and most studies to date have focused on high-frequency vibration. This study aimed to investigate the effect of low-frequency lower-body vibration (LBV) on post-exercise changes in heart rate variability and peripheral arterial tone. Ten men and 9 women aged 20 to 25 were recruited for this study. Each subject visited the testing room three times with at least 2 days in between. Each time, the subject received one of the three different vibration frequencies (0, 5, and 15 Hz) in a random order in the sitting position for 10 minutes. LBV was performed immediately after a static standing (control) test and 3-min-step test. Heart rate variability and digital volume pulse wave were recorded during the vibration phase (V1: vibration 0-5 minutes; V2: 6-10 minutes) and the recovery phase (Rc1: recovery phase 11-15 minutes; Rc2: 16-20 minutes). The result of digital pulse wave analysis showed that the reflection index (RI) under 15 Hz decreased during V1. Heart rate of the 15-Hz group also decreased during Rc1 and Rc2. According to the analysis of heart rate variability, low-frequency power/high-frequency power (LF/HF) decreased and normalized high-frequency power (nHF) increased during V2, Rc1 and Rc2 under 15 Hz and, during Rc2 under 5 Hz vibration. This study confirmed that the application of low-frequency LBV after exercise can reduce peripheral vascular tone, accelerate heart rate recovery, decrease cardiac sympathetic nerve activity, and promote parasympathetic nerve activity. The effect was more pronounced at 15 Hz than at 5 Hz. The findings provide a method to accelerate cardiovascular autonomic recovery after exercise.

A randomized controlled trial of enhancing hypoxia-mediated right cardiac mechanics and reducing afterload after high intensity interval training in sedentary men.

Hypoxic exposure increases right ventricular (RV) afterload by triggering pulmonary hypertension, with consequent effects on the structure and function of the RV. Improved myocardial contractility is a critical circulatory adaptation to exercise training. However, the types of exercise that enhance right cardiac mechanics during hypoxic stress have not yet been identified. This study investigated how high-intensity interval training (HIIT) and moderate-intensity continuous training (MICT) influence right cardiac mechanics during hypoxic exercise A total of 54 young and healthy sedentary males were randomly selected to engage in either HIIT (3-min intervals at 40% and 80% of oxygen uptake reserve, n = 18) or MICT (sustained 60% of oxygen uptake reserve, n = 18) for 30 min/day and 5 days/week for 6 weeks or were included in a control group (CTL, n = 18) that did not engage in any exercise. The primary outcome was the change in right cardiac mechanics during semiupright bicycle exercise under hypoxic conditions (i.e., 50 watts under 12% FiO2 for 3 min) as measured by two-dimensional speckle tracking echocardiography.: After 6 weeks of training, HIIT was superior to MICT in improving maximal oxygen consumption (VO2max). Furthermore, the HIIT group showed reduced pulmonary vascular resistance (PVR, pre-HIIT:1.16 ± 0.05 WU; post-HIIT:1.05 ± 0.05 WU, p < 0.05) as well as an elevated right ventricular ejection fraction (RVEF, pre-HIIT: 59.5 ± 6.0%; post-HIIT: 69.1 ± 2.8%, p < 0.05) during hypoxic exercise, coupled with a significant enhancement of the right atrial (RA) reservoir and conduit functions. HIIT is superior to MICT in dilating RV chamber and reducing radial strain but ameliorating radial strain rate in either systole (post-HIIT: 2.78 ± 0.14 s-1; post-MICT: 2.27 ± 0.12 s-1, p < 0.05) or diastole (post-HIIT: - 2.63 ± 0.12 s-1; post-MICT: - 2.36 ± 0.18 s-1, p < 0.05). In the correlation analysis, the changes in RVEF were directly associated with improved RA reservoir (r = 0.60, p < 0.05) and conduit functions (r = 0.64, p < 0.01) but inversely associated with the change in RV radial strain (r = - 0.70, p < 0.01) and PVR (r = - 0.70, p < 0.01) caused by HIIT. HIIT is superior to MICT in improving right cardiac mechanics by simultaneously increasing RA reservoir and conduit functions and decreasing PVR during hypoxic exercise.

Eccentric Cycling Training Improves Erythrocyte Antioxidant and Oxygen Releasing Capacity Associated with Enhanced Anaerobic Glycolysis and Intracellular Acidosis.

The antioxidant capacity of erythrocytes protects individuals against the harmful effects of oxidative stress. Despite improved hemodynamic efficiency, the effect of eccentric cycling training (ECT) on erythrocyte antioxidative capacity remains unclear. This study investigates how ECT affects erythrocyte antioxidative capacity and metabolism in sedentary males. Thirty-six sedentary healthy males were randomly assigned to either concentric cycling training (CCT, n = 12) or ECT (n = 12) at 60% of the maximal workload for 30 min/day, 5 days/week for 6 weeks or to a control group (n = 12) that did not receive an exercise intervention. A graded exercise test (GXT) was performed before and after the intervention. Erythrocyte metabolic characteristics and O2 release capacity were determined by UPLC-MS and high-resolution respirometry, respectively. An acute GXT depleted Glutathione (GSH), accumulated Glutathione disulfide (GSSG), and elevated the GSSG/GSH ratio, whereas both CCT and ECT attenuated the extent of the elevated GSSG/GSH ratio caused by a GXT. Moreover, the two exercise regimens upregulated glycolysis and increased glucose consumption and lactate production, leading to intracellular acidosis and facilitation of O2 release from erythrocytes. Both CCT and ECT enhance antioxidative capacity against severe exercise-evoked circulatory oxidative stress. Moreover, the two exercise regimens activate erythrocyte glycolysis, resulting in lowered intracellular pH and enhanced O2 released from erythrocytes.

Cycling Exercise Training Enhances Platelet Mitochondrial Bioenergetics in Patients with Peripheral Arterial Disease: A Randomized Controlled Trial.

Exercise training influences the risk of vascular thrombosis in patients with peripheral arterial disease (PAD). Mitochondrial functionalities in platelets involve the cellular bioenergetics and thrombogenesis. This study aimed to elucidate the effect of cycling exercise training (CET) on platelet mitochondrial bioenergetics in PAD patients. Forty randomly selected patients with PAD engaged in general rehabilitation (GR) with CET (i.e., cycling exercise at ventilation threshold for 30 minute/day, 3 days/week) (GR + CET, n = 20) or to a control group that only received GR course (n = 20) for 12 weeks. Systemic aerobic capacity and platelet mitochondrial bioenergetics that included oxidative phosphorylation (OXPHOS) and electron transport system (ETS) were measured using automatic gas analysis and high-resolution respirometry, respectively. The experimental results demonstrated that GR + CET for 12 weeks significantly (1) elevated VO2peak and lowered VE-VCO2 slope, (2) raised resting ankle-brachial index and enhanced cardiac output response to exercise, (3) increased the distance in 6-minute walk test and raised the Short Form-36 physical/mental component scores, and (4) enhanced capacities of mitochondrial OXPHOS and ETS in platelets by activating FADH2 (complex II)-dependent pathway. Moreover, changes in VO2peak levels were positively associated with changes in platelet OXPHOS and ETS capacities. However, no significant changes in systemic aerobic capacity, platelet mitochondrial bioenergetics, and health-related quality of life (HRQoL) occurred following GR alone. Hence, we conclude that CET effectively increases the capacities of platelet mitochondrial bioenergetics by enhancing complex II activity in patients with PAD. Moreover, the exercise regimen also enhanced functional exercise capacity, consequently improving HRQoL in PAD patients.

Circulating MicroRNA-486 and MicroRNA-146a serve as potential biomarkers of sarcopenia in the older adults.

BACKGROUND: Age-related sarcopenia meaningfully increases the risks of functional limitations and mortality in the older adults. Although circulating microRNAs (c-miRNAs) are associated with aging-related cellular senescence and inflammation, the relationships between c-miRNAs and sarcopenia in the older adults remain unclear. This study investigates whether circulating myo-miRNAs and inflammation-related miRNAs are associated with sarcopenia in the older adults. METHODS: This investigation recruited 77 eligible subjects (41 males and 36 females) from 597 community-dwelling older adults, and then divided them into normal (n = 24), dynapenic (loss of muscular function without mass, n = 35), and sarcopenic groups (loss of muscular function with mass, n = 18). Moreover, myo- (c-miRNA-133a and c-miRNA-486) and inflammation- (c-miRNA-21 and c-miRNA-146a) related miRNAs, as well as, inflammatory-related cytokine and peroxide levels in plasma were determined using quantitative polymerase chain reaction and ELISA, respectively. RESULTS: Sarcopenic group exhibited lesser skeletal muscle mass index (SMI), handgrip strength, and gait speed, as well as, lower c-miR-486 and c-miR-146a levels, compared to those of normal and dynapenic groups. Moreover, c-miR-486 level was positively related to SMI (r = 0.334, P = 0.003), whereas c-miR-146a level was positively associated with SMI (r = 0.240, P = 0.035) and handgrip strength (r = 0.253, P = 0.027). In the receiver operating characteristic analysis for predicting sarcopenia, the area under the curve in c-miR-486 was 0.708 (95% confidence interval: 0.561-0.855, P = 0.008) and c-miR-146a was 0.676 (95% CI: 0.551-0.801, P = 0.024). However, no significant relationships were observed between SMI/handgrip strength/gait speed and plasma myeloperoxidase/interleukin-1훽/interleukin-6 levels. CONCLUSIONS: Myo-miRNA (c-miR-486) and inflammation-related miRNA (c-miR-146a) are superior to inflammatory peroxide/cytokines in plasma for serving as critical biomarkers of age-related sarcopenia.

Supervised Cycling Training Improves Erythrocyte Rheology in Individuals With Peripheral Arterial Disease.

Peripheral arterial disease (PAD) results in insufficient flow to lower extremities. Aerobic exercise provides health benefits for individuals with PAD, but basic science behind it is still debated. Twenty-one PAD patients aged about 70 years with female/male as 7/14 were recruited. Among them, 11 were randomized to have supervised cycling training (SCT) and 10 to receive general healthcare (GHC) as controls. SCT participants completed 36 sessions of SCT at the first ventilation threshold within 12 weeks and the controls received GHC for 12 weeks. Ankle-brachial index (ABI), 6-min walk test (6MWT), peak oxygen consumption ( V ˙ O2peak), minute ventilation ( V ˙ E), minute carbon dioxide production ( V ˙ CO2), erythrocyte rheology, including the maximal elongation index (EImax) and shear stress at 50% of maximal elongation (SS1/2), and the Short Form-36 (SF-36) questionnaire for quality of life (QoL) were assessed before and 12 weeks after initial visit. SCT significantly decreased the SS1/2 as well as SS1/2 to EImax ratio (SS1/2/EImax) and increased the erythrocyte osmolality in the hypertonic region as well as the area under EI-osmolality curve. The supervised exercise-induced improvement of erythrocyte deformability could contribute to the increased peripheral tissue O2 delivery and was possibly related with increased V ˙ O2peak. The physiological benefit was associated with significantly increased ABI, 6-min walking distance, cardiorespiratory fitness, and SF-36 score. However, no significant changes in aerobic capacity and erythrocyte rheological properties were observed after 12-week of GHC. In conclusion, SCT improves aerobic capacity by enhancing erythrocyte membrane deformability and consequently promotes QoL in PAD patients.

Increased serum brain-derived neurotrophic factor with high-intensity interval training in stroke patients: A randomized controlled trial.

BACKGROUND: Physiological adaptations of stroke patients after high-intensity interval training (HIIT) and moderate-intensity continuous training (MICT) remain unclear. OBJECTIVE: This study determined the HIIT and MICT effects on aerobic capacity, cerebral oxygenation, peak cardiac output (CO), and serum brain-derived neurotrophic factor (BDNF) in stroke patients. METHODS: We included 23 stroke patients with age about 55 years and stroke duration>24 months; participants completed 36 sessions of exercise training for 30min; 13 were randomly assigned to perform MICT at 60% of peak oxygen consumption (VO2peak) and 10 to perform HIIT at alternating 80% (3min) and 40% (3min) VO2peak. Before and after interventions, we evaluated VO2peak, peak CO, arteriovenous oxygen difference (AV O2diff), bilateral frontal cortex oxygenation (relative changes of oxyhemoglobin Δ[O2Hb], deoxyhemoglobin Δ[HHb], and total hemoglobin Δ[THb] levels), serum brain-derived neurotrophic factor (BDNF) level, and fluorescent cell staining for neuron morphology and percentage of cell-bearing neurites (% neurites). RESULTS: HIIT induced significant increases in VO2peak (P=0.008), CO (P=0.038), Δ[HHb] (P=0.046), Δ[THb] (P=0.046), and serum BDNF level (P=0.012). The improvement in VO2peak was significantly greater with HIIT than MICT (20.7% vs. 9.8%, P=0.031), as was AV O2diff (P=0.041), Δ[HHb] (P=0.027), and serum BDNF level (P<0.001). HIIT facilitated neuron dendritic protrusions (greater % neurites, P=0.012) with prominent redistribution of mitochondria. CONCLUSION: As compared with MICT, HIIT-improved aerobic capacity by increasing systemic tissue O2 extraction in stroke patients. Increased cerebral O2 utilization in the involved hemisphere was also identified after HIIT. These physiological adaptations may be associated with increased serum BDNF level. In vitro dendritic growth in neurons treated with serum from HIIT participants may imply significant effects on neuron activities as compared with MICT. CLINICALTRIALS. GOV IDENTIFIER: NCT04135391.

Weight control in older adults with knee osteoarthritis: a qualitative study.

BACKGROUND: Knee osteoarthritis (OA) affects mostly older adults and its primary risk factor is obesity. This study sought to understand weight-control strategies, facilitators of and barriers toward weight control in older adults with knee OA who preferred not to undergo physician-recommended total knee arthroplasty. METHODS: For this qualitative descriptive study, older outpatients (N = 118) were recruited from orthopedic clinics at three hospitals. Data were collected through face-to face, individual in-depth interviews using a semi-structured interview guide and analyzed using content analysis. RESULTS: Among participants, only 25.4% had body weight in the normal range and 55.9% reported having controlled their weight. Their most common weight-control strategies were to control diet and to exercise and control diet together. Weight control was facilitated by desiring good health, wanting to improve walking or movement, perceiving that they had gained weight, wanting to look good, and advice from healthcare providers. Common barriers to participants' weight control were perceiving that dietary control was not needed, controlling appetite was difficult, dietary control was difficult, and not eating was physically uncomfortable. CONCLUSIONS: Our findings help healthcare providers understand how older adults with knee OA perceive weight control and serve as a reference for developing weight-control programs. Health care providers can integrate these identified facilitators and barriers into a weight-control intervention program. The importance of weighing oneself every day, the meaning of body mass index, consulting with a dietician regularly to control weight, and providing appropriate knowledge about aging and weight control should also be included in any weight-control intervention program.