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.

Association Between Herpes Simplex Virus II Infection and Rheumatoid Arthritis in US Adults: A Population-Based Propensity Score-Matching Study.

BACKGROUND/OBJECTIVE: The potential correlation between herpes simplex virus (HSV) and human papillomavirus (HPV) infections and rheumatoid arthritis (RA) has not been definitively established. Further research is needed to determine the relationship between the development of RA and the presence of these viral infections. METHODS: A case-control study was conducted with data from the National Health and Nutrition Examination Survey between 2009 and 2014. Our analysis examined the association between HSV I, HSV II, HPV oral polymerase chain reaction (PCR), HPV vaginal PCR, and RA. We identified adults aged 20 to 49 years with a primary diagnosis of RA using the National Health and Nutrition Examination Survey database codes (MCQ191 = 1 [years 2009-2010]; MCQ195 = 2 [years 2011-2014]) and excluded patients with incomplete data on key variables and primary outcomes. RESULTS: The study included 8620 patients, with 150 patients diagnosed with RA and 1500 patients without RA. Patients with RA had a significantly higher prevalence of HSV II infection compared with those without RA (36.34% vs. 24.72%, p = 0.015) after propensity score matching. No significant differences were observed for HSV I, HPV oral PCR, and HPV vaginal PCR between the 2 groups. Patients with RA were older; were more likely to be female, obese, and non-Hispanic White; and had a higher prevalence of comorbidities than those without RA. CONCLUSIONS: This population-based propensity score-matching study provides evidence of an association between HSV II infection and RA in US adults. Further research is needed to fully elucidate the relationship between viral infections and RA, with the aim of developing effective risk reduction strategies and innovative treatments for RA.

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.

Trainability for cardiopulmonary fitness is low in patients with peripheral artery disease.

AIMS: In peripheral arterial disease (PAD) patients, exercise therapy is recommended to relieve leg symptoms as noted in the 2016 AHA/ACC and 2017 ESC/ESVS guidelines. We assessed the trainability for cardiopulmonary fitness (CPF) and quality of life (QOL); three distinct patient types, including PAD, heart failure (HF), and stroke, were compared. METHODS AND RESULTS: This is a multicenter, retrospective analysis of prospectively collected data from three clinical studies. Data from 123 patients who completed 36 sessions of supervised aerobic training of moderate intensity were analyzed, including 28 PAD, 55 HF, and 40 stroke patients. Before and after training, cardiopulmonary exercise testing with noninvasive cardiac output monitoring and QOL evaluation using a 36-Item Short Form Survey (SF-36) were performed. Non-response was defined as a negative change in post-training value compared to pre-training value. The result showed improvement in CPF in all three groups. However, CRF increased lesser in the PAD group than in the HF and stroke groups; physical and mental component scores (MCS) of SF-36 exhibited similar pattern. Non-response rates of peak V̇O2, oxygen uptake efficiency slope, and MCS were higher in the PAD. In the PAD group, non-responders regarding peak V̇O2 had a higher pulse wave velocity than responders. CONCLUSIONS: In PAD patients following exercise therapy, CRF and QOL improved less on average; their non-response rate was also higher compared to HF or stroke patients. Therefore, a higher dose of exercise might be needed to elicit adaptation in PAD patients, especially those with high pulse wave velocity.

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 .

Using T1 mapping indices to evaluate muscle function and predict conservative treatment outcomes in diabetic patients with peripheral arterial disease.

OBJECTIVES: To investigate interstitial muscle fibrosis via T1 mapping indices and its relationships with muscle function and conservative treatment outcomes. METHODS: A total of 49 DM patients with PAD were prospectively recruited from 2016 to 2017. All PAD patients underwent pre-treatment MRI with conservative treatment via a rehabilitation program and antiplatelet therapy. The need to require percutaneous transluminal angioplasty intervention was recorded as intolerance to conservative treatment outcomes. We quantified calf interstitial muscle fibrosis using T1 mapping indices (native T1, post-contrast T1, and the extracellular volume fraction [ECV]). Muscle function was evaluated using a 6-min walking test (6MWT) and a 3-min stepping test (3MST). PAD patients were divided into two groups according to their tolerance or intolerance of the conservative treatment. Pearson's correlation, reproducibility, and multivariable Cox hazard analyses were performed with p < 0.05 indicating statistical significance. RESULTS: Among the T1 mapping indices in the posterior compartment of the calf in PAD patients, the native T1 value was significantly correlated with 6MWT (r = -0.422, p = 0.010) and 3MST (r = -0.427, p = 0.009). All T1 mapping indices showed excellent intra-observer and inter-observer correlations. ECV was an independent predictor of conservative treatment intolerance (average ECV, hazard ratio: 1.045, 95% confidence interval: 1.011-1.079, p = 0.009). CONCLUSIONS: T1 mapping measurements are reproducible with excellent intra-observer and inter-observer correlations. T1 mapping indices may be predictive of treatment and functional outcomes and carry promise in patient evaluation. TRIAL REGISTRATION: Clinical Trials Identifier: NCT02850432 . KEY POINTS: • T1 mapping measurements of the calf muscles are reproducible with excellent intra-observer and inter-observer correlations (0.98 and 0.95 for anterior and posterior compartment muscle extracellular volume matrix [ECV] measurements, respectively). • ECV is shown to independently predict conservative treatment intolerance. • T1 mapping indices may be predictive of treatment and functional outcomes and carry promise in patient evaluation.

Factors Associated With Participation Rate and Predictive of Improvement After Cardiac Rehabilitation in Patients With Heart Failure.

PURPOSE: Patients with heart failure (HF) are often limited in their ability to perform exercise. Cardiac rehabilitation (CR) improves aerobic capacity and quality of life (QOL) and is recommended for patients with clinically stable HF; however, it is underutilized. The aim of this study was to investigate the factors associated with participation and completion rates and predictive of improvement after phase II CR in patients with HF. METHODS: Participation and completion rates were calculated for all patients with HF enrolled in a multidisciplinary management program from October 2008 to December 2018. Functional capacity and QOL were estimated. In patients undergoing CR, changes in peak oxygen uptake (V˙ o2peak ) were measured. RESULTS: Of 662 patients enrolled, 448 (68%) completed the cardiopulmonary exercise test (CPX). Phase II CR was recommended in 411 patients, of whom 291 (71%) participated in CR. Participation was significantly related to sex and the time interval in days between hospital discharge and the CPX. Overall, 171 patients completed 36 sessions of CR (with a completion rate of 59%). During CR, there were 18 (6%) adverse events. Cardiac rehabilitation was associated with improvement in V˙ o2peak from 1153 ± 393 to 1342 ± 470 mL/min (a 16% improvement; P < .001) and in QOL. The independent predictors of increase in V˙ o2peak included sex, age, diabetes mellitus, and entry V˙ o2peak . CONCLUSIONS: In patients with HF, factors associated with CR participation rate included sex and days between hospital discharge and the CPX. Participation in CR improved V˙ o2peak and QOL. The improvement was related to male sex, younger age, no diabetes mellitus, and higher entry V˙ o2peak .

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.

Associations Between Sarcopenia, Heart Failure and Myocardial Infarction in Patients With Systemic Lupus Erythematosus and Rheumatoid Arthritis.

Objectives: To evaluate associations between sarcopenia, type of autoimmune disease and risk of heart failure (HF) and myocardial infarction (MI) in patients with systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA). Methods: In this population-based, cross-sectional study, discharge data from the 2005-2014 US Nationwide Inpatient Sample (NIS) of hospitalized patients with SLE or RA were extracted and analyzed. Univariate and multivariable regression analyses were conducted to determine associations between sarcopenia, type of autoimmune disease and risk of HF/MI. Results: After exclusions, 781,199 hospitalized patients diagnosed with SLE or RA were included. Among the study cohort, 127,812 (16.4%) were hospitalized with HF, and 12,781 (1.6%) were hospitalized with MI. Sarcopenia was found in only 0.1% of HF/MI patients. Logistic regression analyses revealed that sarcopenia was not significantly associated with presence of either HF or MI. Patients with RA had significantly lower odds of HF than SLE patients (aOR = 0.77, 95%CI: 0.76, 0.79) or MI (aOR = 0.86, 95%CI: 0.82, 0.91). Conclusion: In the US, among hospitalized adults diagnosed with SLE or RA, patients with RA are significantly less likely to have HF or MI than those with SLE. Whether sarcopenia leads to increased HF or MI remains inconclusive. Further studies are warranted to investigate the pathophysiology underlying discrepancies between RA and SLE regarding risk for MI or HF.

Artificial-Intelligence-Assisted Discovery of Genetic Factors for Precision Medicine of Antiplatelet Therapy in Diabetic Peripheral Artery Disease.

An increased risk of cardiovascular events was identified in patients with peripheral artery disease (PAD). Clopidogrel is one of the most widely used antiplatelet medications. However, there are heterogeneous outcomes when clopidogrel is used to prevent cardiovascular events in PAD patients. Here, we use an artificial intelligence (AI)-assisted methodology to identify genetic factors potentially involved in the clopidogrel-resistant mechanism, which is currently unclear. Several discoveries can be pinpointed. Firstly, a high proportion (>50%) of clopidogrel resistance was found among diabetic PAD patients in Taiwan. Interestingly, our result suggests that platelet function test-guided antiplatelet therapy appears to reduce the post-interventional occurrence of major adverse cerebrovascular and cardiac events in diabetic PAD patients. Secondly, AI-assisted genome-wide association study of a single-nucleotide polymorphism (SNP) database identified a SNP signature composed of 20 SNPs, which are mapped into 9 protein-coding genes (SLC37A2, IQSEC1, WASHC3, PSD3, BTBD7, GLIS3, PRDM11, LRBA1, and CNR1). Finally, analysis of the protein connectivity map revealed that LRBA, GLIS3, BTBD7, IQSEC1, and PSD3 appear to form a protein interaction network. Intriguingly, the genetic factors seem to pinpoint a pathway related to endocytosis and recycling of P2Y12 receptor, which is the drug target of clopidogrel. Our findings reveal that a combination of AI-assisted discovery of SNP signatures and clinical parameters has the potential to develop an ethnic-specific precision medicine for antiplatelet therapy in diabetic PAD patients.

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.

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.

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.

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.

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.