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Background Emerging evidence suggests that DNA methylation can be affected by physical activities and is associated with cardiac fibrosis. The translational research examined the implications of DNA methylation presentations behind 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 cardiopulmonary exercise test for peak oxygen consumption (⩒O2peak). Afterwards, they underwent 36 sessions of HIIT at alternating 80% and 40% of ⩒O2peak for 30 min per session in 3–4 months. Human serum from 11 participants, linking cell biology to clinical presentations, was used to investigate exercise effects on cardiac fibrosis. Primary human cardiac fibroblasts (HCFs) incubated in patient serum for cell behaviors, proteomics (n = 6) and DNA methylation profiling (n = 3) were performed. All measurements were followed after completing HIIT. Results An increase of ⩒O2peak along with decreased b-type natriuretic peptide was observed after HIIT. Significantly decreased left ventricle (LV) myocardium fibrosis by 8–12% at middle and apical myocardial segments, decreased LV volume, and increased LV ejection fraction were identified after HIIT. 49 in 1222 identified proteins were significantly involved in the HIIT-induced altered HCF activities. A significant hypermethylation on acyl-CoA dehydrogenase very long chain (ACADVL) gene was identified. Downstream caspases-mediated actin disassembly and cell death pathway were activated after HIIT. Conclusions HIIT is associated with hypermethylation of ACADVL to impede HCF activities. This exercise-associated epigenetic reprogramming may contribute to reduce cardiac fibrosis and furthermore, promotes cardiorespiratory fitness in HF patients. Trial registration : NCT04038723. Registered 31 July 2019, https://clinicaltrials.gov/ct2/show/NCT04038723.

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. Key points High-frequency (> 20 Hz) vibration applied at rest or during exercise was confirmed to facilitate peripheral vasodilation. On the other hand, the effect of low frequency (< 20Hz) vibration on the autonomic cardiovascular system applied in the post-exercise period was scarcely investigated and remained unclear. Application of low-frequency low-body vibration after exercise can reduce peripheral vascular tone, accelerate heart rate recovery, decrease cardiac sympathetic nerve activity, and promote parasympathetic nerve activity. The effect of low-frequency LBV on post-exercise cardiovascular change was more pronounced at 15 Hz than at 5 Hz.

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.

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.

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.

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 ClinicalTrial.gov: NCT04156724; IRB number: C108032.

Whether near-infrared spectroscopy (NIRS) is a convenient and accurate method of determining first and second ventilatory thresholds (VT1 and VT2) using raw data remains unknown. This study investigated the reliability and validity of VT1 and VT2 determined by NIRS skeletal muscle hemodynamic raw data via a polynomial regression model. A total of 100 male students were recruited and performed maximal cycling exercises while their cardiopulmonary and NIRS muscle hemodynamic data were measured. The criterion validity of VT1VET and VT2VET were determined using a traditional V-slope and ventilatory efficiency. Statistical significance was set at α = . 05. There was high reproducibility of VT1NIRS and VT2NIRS determined by a NIRS polynomial regression model during exercise (VT1NIRS, r = 0.94; VT2NIRS, r = 0.93). There were high correlations of VT1VET vs VT1NIRS (r = 0.93, p

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).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.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.These results suggest social support for persons with DM should be continually assessed following hip-fracture surgery.

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.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.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.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.

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.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).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 1β (MIP-1 β) 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.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.

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.

Pathological erythrocyte aggregation reduces capillary perfusion and oxygen transfer to tissue, which is determined by the negative surface charge on the erythrocyte membrane (intrinsic aggregability) and fibrinogen–erythrocyte interaction (extrinsic factor). Exercise-induced oxidative stress is important for rheological adaptation to training but may also cause erythrocyte senescence. This study clarifies the effects of hypoxic exercise training on intrinsic/extrinsic factors of aggregation. In total, 60 healthy sedentary males were randomly assigned to either hypoxic (HE, FIO2 = 0.15) or normoxic exercise training (NE, FIO2 = 0.21) groups for 30 min·d−1, 5 d·wk−1 for 6 weeks at 60 % of the maximum work rate or to a control group (CTL). A hypoxia exercise test (HET, FIO2 = 0.12) was performed before and after the intervention. Erythrocyte aggregation was assessed by ektacytometry, and fibrinogen binding affinity and senescence biomarkers were assessed by flow cytometry. An acute 12% oxygen HET significantly enhanced erythrocyte global aggregation through intrinsic aggregability. Resting aggregation is promoted by both intrinsic aggregability and fibrinogen binding probability and force after HE, whereas NE is mainly associated with ameliorated fibrinogen–erythrocyte interactions. The HET still facilitated global aggregation after HE because of the augmented fibrinogen-related factors, even though the intrinsic factor was suppressed. Additionally, HE further increased reticulocyte counts while reducing the expression of CD47 and CD147. Resting aggregability is promoted by both intrinsic and extrinsic factors after HE, whereas NE is mainly associated with an ameliorated affinity for fibrinogen. Although an accelerated turnover rate was observed, HE further led to erythrocyte senescence.

Background Adherence to rehabilitation is beneficial to patients with hip fracture. However, the relationships between different levels of adherence and postoperative recovery among older adults after hip fracture have not been addressed thoroughly in the literature. Objectives The aims of this study were to explore the trajectories of adherence to home-based rehabilitation during the 12-month period after hospital discharge and to examine the effects of adhering to prescribed home-based rehabilitation on postoperative recovery of physical functions. Methods We employed a secondary data analysis, and 88 hip-fractured older adults with diabetes were recruited. The Chinese Barthel Index was used to measure daily physical functions, a goniometer was used to measure range of motion, and the MicroFET2 dynamometer was used to measure muscle power. Adherence was measured as the rate of adherence to the suggested frequency of home-based rehabilitation activities. Results Adherence to home-based rehabilitation decreased over time. The high-adherence group was more likely to recover prefracture physical functions than was the low-adherence group, and the high-adherence group had better self-care abilities, greater range of motion for ankle extension, and higher muscular strength on both adduction and abduction than did the low-adherence group. Discussion The results of our study suggest that patients adhere to more than 50% of prescribed rehabilitation. Future studies should continue to explore interventions to enhance rehabilitation adherence after hospital discharge.

To explore the impact of diabetic peripheral neuropathy (DPN) on the recovery of older persons with diabetes mellitus (DM) after hip-fracture surgery.Secondary data for this study came from a clinical trial on the effectiveness of a DM-specific care model for 176 older persons (age ≥ 60) with DM over 2 years following hip-fracture surgery at a medical center in Taiwan. In the original trial, the experimental group (n = 88) received DM-specific care comprising diabetes care plus subacute care, and the control group (n = 88) received only usual care.DPN was assessed using the Michigan Neuropathy Screening Instrument. Outcomes of self-care ability in activities of daily living (ADL), health-related quality of life (HRQoL), and depressive symptoms were assessed 1, 3, 6, 12, 18, 24 months following hospital discharge using the Chinese Barthel Index and Chinese-version instrumental ADL (IADL) scale; the SF-36 Taiwan version; and the Chinese-version Geriatric Depression Scale, short form, respectively.After controlling for covariates, participants with DPN had 8.38 fewer points in ADL performance, 0.49 fewer points in IADL performance, and 2.33 fewer points in the physical component summary (PCS) of HRQoL than participants without DPN at 3 months following discharge. During the first year following discharge, the rate of improvement increased less for PCS (β = -0.45, p 0.05), but more for the mental component summary (β = 0.49, p 0.05) for those with DPN than for those without. During the second year, the rate of decline in physical function-related HRQoL increased slightly more for those with DPN than for those without (β = 0.03, p 0.05).DPN adversely affected ADL performance, IADL performance, and physical function-related health outcomes for older persons recovering from hip-fracture surgery. These results suggest that older patients with DM recovering from hip-fracture surgery should be assessed and managed for DPN.

Introduction Improved myocardial contractility is a critical circulatory adaptation to exercise training. However, the types of exercise that enhance left ventricular (LV) contractile and diastolic functions have not yet been established. This study investigated how high-intensity interval training (HIIT) and moderate-intensity continuous training (MICT) influence LV mechanics during exercise. Methods Fifty-four healthy sedentary men were randomized to engage in either HIIT (3-min intervals at 40% and 80% of V˙O2max, n = 18) or MICT (sustained 60% of V˙O2max, n = 18) for 30 min·d, 5 d·wk for 6 wk or to a control group (n = 18) that did not engage in exercise intervention. LV mechanics during semiupright bicycle exercise tests were measured by two-dimensional speckle-tracking echocardiography. Results Before the interventions, acute bicycle exercise increased (i) peak basal/apical radial and circumferential and peak longitudinal strains and strain rates, (ii) peak basal/apical rotations and torsion, and (iii) peak systolic twisting and early diastolic untwisting velocities in the LV. After the interventions, the HIIT group exhibited greater LV mass and diastolic internal diameter as well as higher ratio of E wave to A wave and early diastolic propagation velocity than did the MICT group. Despite decreased peak apical rotation and torsion, HIIT enhanced peak apical radial strain and strain rate as well as shortened the time to reach peak untwisting velocity in the LV during exercise. However, the LV mechanics during exercise were unchanged in the control group. Conclusion HIIT but not MICT induces eccentric myocardial hypertrophy. Moreover, HIIT effectively improves the LV mechanics during exercise by increasing contractile and diastolic functions.

Introduction Physical exercise or hypoxic exposure influences erythrocyte susceptibility to osmotic stress, and the aquaporin 1 (AQP1) facilitates the transport of water in erythrocytes. This study investigated whether high-intensity interval training (HIIT) and moderate-intensity continuous training (MICT) affect erythrocyte osmotic deformability by modulating AQP1 function under hypoxic stress. Methods Forty-five healthy sedentary males were randomized to engage in either HIIT (3-min intervals at 40% and 80% V˙O2 reserve, n = 15) or MICT (sustained 60% V˙O2 reserve, n = 15) on a bicycle ergometer for 30 min·d, 5 d·wk for 6 wk, or to a control group that did not perform any exercise (n = 15). All subjects were analyzed with osmotic gradient ektacytometry for assessing erythrocyte membrane stability and osmotic deformability after hypoxic exercise (HE) (100 W under 12%O2 for 30 min). Results Before the intervention, HE increased the shear stress at 50% of maximal elongation (SS1/2) and the ratio of SS1/2 to maximal elongation index (SS1/2/EImax) on erythrocytes pretreated with 50 Pa of shear stress for 30 min and diminished HgCl2-depressed osmolality at 50%EImax (Ohyper). However, both HIIT and MICT for 6 wk diminished the elevations of erythrocyte SS1/2 and SS1/2/EImax caused by HE. Moreover, HIIT also increased contents of erythrocyte AQP1 proteins while enhancing HgCl2-depressed Ohyper and area under elongation index-osmolarity curve after HE. Additionally, changes in erythrocyte AQP1 contents were associated with changes in HgCl2-depressed erythrocyte Ohyper and area under elongation index-osmolarity curve. Conclusions Acute HE reduces erythrocyte membrane stability, whereas either HIIT or MICT attenuates the depression of erythrocyte membrane stability by HE. Moreover, HIIT increases the AQP1 content and facilitates the HgCl2-mediated osmotic deformability of erythrocytes after HE.

Purpose: Hypoxic exposure increases right ventricular (RV) afterload by triggering pulmonary hypertension, with consequent effects on the structure and function of the right ventricle. 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 (HE). Methods: 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 VO2max, n = 18) or MICT (sustained 60% of VO2max, 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. Right cardiac mechanics during semiupright bicycle exercise tests under hypoxic conditions (i.e., 50 watts under 12% FIO2 for 3 min) were measured using two-dimensional speckle-tracking echocardiography. Results: After 6 weeks of training, HIIT was superior to MICT in improving VO2max. Furthermore, the HIIT group showed reduced pulmonary vascular resistance (PVR) as well as an elevated RV ejection fraction (RVEF) under hypoxia, coupled with a significant enhancement of the right atrial (RA) reservoir and conduit functions. HIIT is superior to MICT in dilating the right ventricle and ameliorating radial strain rate but reducing radial strain in either systole or diastole. In the correlation analysis, the changes in RVEF were directly associated with improved RA reservoir and conduit functions but inversely associated with the change in radial RV strain caused by HIIT. Conclusion: HIIT is superior to MICT in improving right cardiac mechanics by simultaneously increasing RA reservoir and conduit functions and decreasing PVR during HE.

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 -1; post-MICT: 2.27 ± 0.12 s-1, p -1; post-MICT: − 2.36 ± 0.18 s-1, p

Background: Age-related sarcopenia meaningfully increases the risks of functional limitations and mortality in the elderly. Although circulating microRNAs (c-miRNAs) are associated with aging-related cellular senescence and inflammation, the relationships between c-miRNAs and sarcopenia in the elderly remain unclear. This study investigates whether circulating myo-miRNAs and inflammation-related miRNAs are associated with sarcopenia in the elderly. Methods: This investigation recruited 77 eligible subjects (41 males and 36 females) from 597 community-dwelling older adults, and then divided 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-1𝛽/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.

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 min/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 (i) elevated VO2peak and lowered VE-VCO2 slope, (ii) raised resting ankle-brachial index and enhanced cardiac output response to exercise, (iii) increased the distance in 6-minute walk test and raised the Short Form-36 physical/mental component scores, and (iv) 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.

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 30 min; 13 were randomly assigned to perform MICT at 60% of peak oxygen consumption (VO2peak) and 10 to perform HIIT at alternating 80% (3 min) and 40% (3 min) 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 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 .

Additional file 1. COREQ (Consolidated criteria for Reporting Qualitative research) Checklist.

Huang, Shu-Chun, Kuo-Cheng Liu, Alice M.K. Wong, Shih-Chieh Chang, and Jong-Shyan Wang. Cardiovascular autonomic response to orthostatic stress under hypoxia in patients with spinal cord injury. High Alt Med Biol. 19:201-207, 2018.Determining whether systemic hypoxia aggravates the severity of autonomic cardiovascular dysfunction in orthostatic stress among patients with spinal cord injuries (SCIs).Twenty-four male patients with chronic SCI whose neurological levels were above T6 were recruited. Twenty-five healthy men were enrolled in the control group. Five-minute supine rest (SR) and head-up tilt (HUT) at 60° were performed in normoxia and after 1 hour, 13.5% fraction of inspired OIn normoxia from SR to HUT, systolic and diastolic BPs declined, SV decreased, and heart rate increased, whereas CO and TPR showed a declining trend in the SCI group. Sympathetic activation and vagal withdrawal were also disclosed in the HRV analysis. In hypoxia, the change of these cardiovascular responses from SR to HUT exhibited no difference to normoxia in the SCI group. No significant difference in arterial desaturation was observed between the two groups (82.9% vs. 80.4%).Cardiovascular adaptation to orthostatic stress is not affected by subacute steady-state hypoxia in chronic SCI patients with neurological levels higher than T6.

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 ± 35.6 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

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

Oxidative stress-induced lymphocyte apoptosis is linked to hypoxemic individuals suffering from cardiopulmonary disorders or exposed to hypoxic environments. What kind of the exercise strategy under hypoxic condition improves exercise performance and simultaneously minimizes lymphocyte dysfunction caused by oxidative stress has not yet been established. This study elucidates how various exercises regimens with/without hypoxia affect lymphocyte apoptosis induced by oxidative stress. A total of 60 sedentary males were randomly divided into five groups. Each group (n = 12) received one of the five interventions: hypoxic-absolute exercise (HAT, 50%Wmax under 15%O2), hypoxic-relative exercise (HRT, 50% heart rate reserve under 15%O2), normoxic exercise (NT, 50%Wmax under 21%O2), hypoxic control (HC, resting under 15%O2), or normoxic control (NC, resting under 21%O2) for 30 min/day, 5 days/week for 4 weeks. Before the intervention, the graded exercise test (GXT, progressive exercise up to VO2max) decreased the surface thiol level on lymphocytes and subsequently augmented the extents of H2O2-induced mitochondria transmembrane potential (MTP) diminishing, caspase 3/8/9 activations, and phosphotidyl serine (PS) exposure in lymphocytes. However, 4 weeks of NT, HRT, or HAT reduced the extents of surface thiol decreasing on lymphocytes and H2O2-induced MTP diminishing, caspase 3/8/9 activations, and PS exposure in lymphocytes following GXT. Moreover, the HAT group exhibited greater improvements in pulmonary ventilation and VO2max than either NT or HRT group did. Exercise training with/without hypoxic exposure effectively alleviates lymphocyte apoptosis induced by oxidative stress following strenuous exercise. However, the HAT is superior to the NT or HRT for enhancing aerobic capacity.

SummaryThe interaction between platelets and monocytes plays a critical role in the pathogenesis and progression of cardiovascular diseases. This study investigated how short-term intensive training (SIT) influences monocyte subset characteristics and exercise-induced monocyte and platelet aggregates (MPAs) following elective coronary bypass (CABG) in cardiac patients. Forty-nine patients hospitalised for CABG were randomised into SIT (N=26) and conventional training (CT, N=23) groups. The SIT subjects underwent supervised aerobic training at 80∼120 % of the ventilatory anaerobic threshold based on sub-maximal exercise tests performed 7 days post-CABG for 20 sessions with two sessions/day and 30 min/session, which were completed within four weeks after surgery. The CT subjects performed light-intensity conditioning exercise for ≤4 sessions. Resting and maximal exercise-mediated monocyte characteristics and MPA were determined before and following intervention. The SIT group had a larger improvement in ventilation efficiency and anaerobic threshold than the CT group; the SIT group exhibited larger reductions in blood monocyte subtypes 1 and 2 (Mono1 and 2) counts at rest than the CT group; the SIT group but not the CT group exhibited attenuated formation of Mono1/platelet hetero-aggregation (MPA1) and CD42b expression on Mono1/2 caused by strenuous exercise; and plasma levels of macrophage inflammatory protein-1β and soluble P-selectin showed similar trends as Mono1/2 and MPA1, respectively. In conclusion, SIT modestly improved aerobic capacity in patients following CABG. Moreover, SIT simultaneously ameliorated the CD42b expression of Mono1/2 cells and maximal exercise-induced MPA1, which may reduce the risk of inflammatory thrombosis.Supplementary Material to this article is available online at www.thrombosis-online.com.

Exercise training (ET) may impact physical fitness by affecting mitochondrial functions. This study aimed to elucidate the effect of ET on aerobic capacity and platelet mitochondrial bioenergetics (MTB) in stroke patients. Among the 30 stroke patients who underwent the traditional rehabilitation program (TRP), 15 were randomly assigned to have ET (50–60% VO2peak for 30 min/day, 5 days/week for 4 weeks), and those remaining received only the TRP (control group). The peak exercise capacity (VO2peak) and platelet MTB, including oxidative phosphorylation (OXPHOS) and the electron transport chain (ETC), were measured through automatic gas analysis and high-resolution respirometry, respectively. The results demonstrated that ET significantly increased the VO2peak (17.7%) and O2 uptake efficiency slope (31.9%) but decreased the ventilation versus CO2 production slope (−7.65%). Patients who underwent ET also had significantly enhanced platelet mitochondrial OXPHOS and ETC by activating the FADH2 (Complex II)-dependent pathway, but depressed plasma myeloperoxidase (−28.4%) and interleukin-6 levels (−29.9%). Moreover, changes in VO2peak levels were positively correlated with changes in platelet OXPHOS and ETC capacities. In conclusion, ET increases the platelet MTB by enhancing Complex II activity in stroke patients. The exercise regimen also enhances aerobic fitness and depresses oxidative stress/pro-inflammatory status in stroke patients.

Objective Consumptive coagulopathy is associated with increased mortality in patients with heart failure (HF). Physical activity influences the risk of major vascular thrombotic events. This study investigates how high-intensity interval training (HIIT) affects the capacity of endogenous thrombin generation (TG) by modulating circulatory procoagulant microparticles (MPs) in HF patients. Methods Thirty-eight HF patients with reduced ejection fraction (HFrEF) and 38 age- and gender-matched normal counterparts (NC) were recruited into this study. The HFrEF group performed HIIT (3-min intervals at 40% and 80%VO2peak) on a bicycle ergometer for 30 min/day, 3 days/week for 12 weeks, whereas the NC group did not receive any form of intervention. Plasma TG kinetics, procoagulant MPs, coagulation-related factors, and oxidative stress/proinflammatory status were analyzed. Results The HFrEF group exhibited (i) less endogenous thrombin potential (ETP) and TG rate, (ii) lower concentration/activity of tissue factor (TF) and counts of TF-rich MPs derived from blood cells, and (iii) higher vascular endothelial shedding and plasma myeloperoxidase and interleukin-6 concentrations, compared to the NC group did. However, HIIT elevated TG rate and TF concentration/activity in plasma, as well as, TF-rich MP counts derived from blood cells in patients with HFrEF. Moreover, the exercise regimen also decreased vascular endothelial shedding and plasma myeloperoxidase and interleukin-6 concentrations in HFrEF patients. Conclusion HFrEF reduces the capacity of endogenous TG in plasma, which is associated with decreased (or consumed) circulatory procoagulant MP levels. However, HIIT alleviates HFrEF-declined endogenous TG capacity and vascular endothelial damage through recuperating TF-related coagulation activity and suppressing oxidative stress/proinflammatory status.