Moderate-intensity aerobic exercise training improves CD8+ tumor-infiltrating lymphocytes effector function by reducing mitochondrial loss.

Aerobic exercise training (AET) has emerged as a strategy to reduce cancer mortality, however, the mechanisms explaining AET on tumor development remain unclear. Tumors escape immune detection by generating immunosuppressive microenvironments and impaired T cell function, which is associated with T cell mitochondrial loss. AET improves mitochondrial content and function, thus we tested whether AET would modulate mitochondrial metabolism in tumor-infiltrating lymphocytes (TIL). Balb/c mice were subjected to a treadmill AET protocol prior to CT26 colon carcinoma cells injection and until tumor harvest. Tissue hypoxia, TIL infiltration and effector function, and mitochondrial content, morphology and function were evaluated. AET reduced tumor growth, improved survival, and decreased tumor hypoxia. An increased CD8+ TIL infiltration, IFN-γ and ATP production promoted by AET was correlated with reduced mitochondrial loss in these cells. Collectively, AET decreases tumor growth partially by increasing CD8+ TIL effector function through an improvement in their mitochondrial content and function.

Association of Sarcopenia and Oxygen Uptake Efficiency Slope in Male Patients With Heart Failure.

PURPOSE: Sarcopenia, the loss of muscle mass and function, is a common comorbidity in patients with heart failure (HF). The skeletal muscle modulates the respiratory response during exercise. However, whether ventilatory behavior is affected by sarcopenia is still unknown. METHODS: We enrolled 169 male patients with HF. Muscle strength was measured by a handgrip dynamometer. Body composition was measured with dual-energy X-ray absorptiometry. Sarcopenia was defined by handgrip strength <27 kg and appendicular lean mass divided by height squared (ALM/height 2 ) <7.0 kg/m 2 . Oxygen uptake efficiency slope (OUES), ventilation (VE), oxygen uptake (VO 2 ), and carbon dioxide output (VCO 2 ) were measured by a cardiopulmonary exercise test. RESULTS: Sarcopenia was identified in 29 patients (17%). At the first ventilatory threshold, VE/VO 2 (36.9 ± 5.9 vs 32.7 ± 6.5; P = .003) and VE/VCO 2 (39.8 ± 7.2 vs 35.3 ± 6.9; P = .004) were higher in patients with sarcopenia compared to those without sarcopenia. At the exercise peak, compared to patients without sarcopenia, patients with sarcopenia had lower OUES (1186 ± 295 vs 1634 ± 564; P < .001), relative VO 2 (16.2 ± 5.0 vs 19.5 ± 6.5 mL/kg/min; P = .01), and VE (47.3 ± 10.1 vs 63.0 ± 18.2 L/min; P < .0001), while VE/VCO 2 (42.9 ± 8.9 vs 38.7 ± 8.4; P = .025) was increased. OUES was positively correlated with ALM/height 2 ( r = 0.36; P < .0001) and handgrip strength ( r = 0.31; P < .001). Hemoglobin (OR = 1.149; 95% CI, 0.842-1.570; P = .038), ALM/height 2 (OR = 2.166; 95% CI, 1.338-3.504; P = .002), and VO 2peak (OR = 1.377; 95% CI, 1.218-1.557; P < .001) were independently associated with OUES adjusted by cofounders. CONCLUSIONS: Our results suggest that sarcopenia is related to impaired ventilatory response during exercise in patients with HF.

Coronary Inflammation by Computed Tomography Pericoronary Fat Attenuation and Increased Cytokines in Young Male Anabolic Androgenic Steroid Users. / Inflamação Coronária Avaliada pela Atenuação de Gordura Pericoronária na Tomografia Computadorizada e Elevação de Citocinas em Usuários Jovens de Esteroides Anabólicos Androgênicos.

BACKGROUND: Anabolic androgenic steroid (AAS) abuse has been associated with coronary artery disease (CAD). Pericoronary fat attenuation (pFA) is a marker of coronary inflammation, which is key in the atherosclerotic process. OBJECTIVE: To evaluate pFA and inflammatory profile in AAS users. METHODS: Twenty strength-trained AAS users (AASU), 20 AAS nonusers (AASNU), and 10 sedentary controls (SC) were evaluated. Coronary inflammation was evaluated by mean pericoronary fat attenuation (mPFA) in the right coronary artery (RCA), left anterior descending coronary artery (LAD), and left circumflex (LCx). Interleukin (IL)-1 (IL-1), IL-6, IL-10, and TNF-alpha were evaluated by optical density (OD) in a spectrophotometer with a 450 nm filter. P<0.05 indicated statistical significance. RESULTS: AASU had higher mPFA in the RCA (-65.87 [70.51-60.70] vs. -78.07 [83.66-72.87] vs.-78.46 [85.41-71.99] Hounsfield Units (HU), respectively, p<0.001) and mPFA in the LAD (-71.47 [76.40-66.61] vs. -79.32 [84.37-74.59] vs. -82.52 [88.44-75.81] HU, respectively, p=0.006) compared with AASNU and SC. mPFA in the LCx was not different between AASU, AASNU, and SC (-72.41 [77.17-70.37] vs. -80.13 [86.22-72.23] vs. -78.29 [80.63-72.29] HU, respectively, p=0.163). AASU compared with AASNU and SC, had higher IL-1, (0.975 [0.847-1.250] vs. 0.437 [0.311-0.565] vs. 0.530 [0.402-0.780] OD, respectively, p=0.002), IL-6 (1.195 [0.947-1.405] vs. 0.427 [0.377-0.577] vs. 0.605 [0.332-0.950] OD, p=0.005) and IL-10 (1.145 [0.920-1.292] vs. 0.477 [0.382-0.591] vs. 0.340 [0.316-0.560] OD, p<0.001). TNF-α was not different between the AASU, AASNU, and SC groups (0.520 [0.250-0.610] vs. 0.377 [0.261-0.548] vs. 0.350 [0.182-430]), respectively. CONCLUSION: Compared with ASSNU and controls, AASU have higher mPFA and higher systemic inflammatory cytokines profile suggesting that AAS may induce coronary atherosclerosis through coronary and systemic inflammation.

FUNDAMENTO: O uso abusivo de esteroides anabólicos androgênicos (EAA) tem sido associado à doença arterial coronariana (DAC). A atenuação de gordura pericoronária (AGp) é um marcador de inflamação coronária, a qual exerce um papel chave no processo aterosclerótico. OBJETIVO: Avaliar AGp e perfil inflamatório em usuários de EAA. MÉTODO: Vinte indivíduos que realizavam treinamento de força, usuários de EAA (UEAA), 20 não usuários de EAA (NUEAA), e 10 indivíduos sedentários controle (SC) foram avaliados. Inflamação coronária foi avaliada por atenuação de gordura pericoronária média (AGPm) artéria coronária direita (ACD), artéria descendente anterior esquerda (ADA) e artéria circunflexa (ACX). Interleucina (IL)-1 (IL-1), IL-6, IL-10, e TNF-alfa foram avaliados por densidade ótica (DO) em um espectrofotômetro com um filtro de 450 nm. Um p<0,05 indicou significância estatística. RESULTADOS: Os UEAA apresentaram maior AGPm na ACD [-65,87 (70,51-60,70) vs. -78,07 (83,66-72,87) vs.-78,46 (85,41-71,99] unidades Hounsfield (HU), respectivamente, p<0,001) e AGPm na ADA [-71,47 (76,40-66,610 vs. -79,32 (84,37-74,59) vs. -82,52 (88,44-75,81) HU, respectivamente, p=0,006) em comparação aos NUEAA e CS. A AGPm na ACX não foi diferente entre os grupos UEAA, NUEAA e CS [-72,41 (77,17-70,37) vs. -80,13 (86,22-72,23) vs. -78,29 (80,63-72,29) HU, respectivamente, p=0,163). Em comparação aos NUEAA e aos CS, o grupo UEAA apresentaram maiores níveis de IL-1 [0,975 (0,847-1,250) vs. 0,437 (0,311-0,565) vs. 0,530 (0,402-0,780) DO, respectivamente, p=0,002), IL-6 [1,195 (0,947-1,405) vs. 0,427 (0,377-0,577) vs. 0,605 (0,332-0,950) DO, p=0,005) e IL-10 [1,145 (0,920-1,292) vs. 0,477 (0,382-0,591) vs. 0,340 (0,316-0,560) DO, p<0,001]. TNF-α não foi diferente entre os grupos UEAA, NUEAA e CS [0,520 (0,250-0,610) vs. 0,377 (0.261-0,548) vs. 0,350 (0,182-430)]. CONCLUSÃO: Em comparação aos NUEAA e controles, os UEAA apresentam maior AGPm e maior perfil de citocinas inflamatórias sistêmicas, sugerindo que os EAA podem induzir aterosclerose por inflamação coronária e sistêmica.

Effects of exercise on platelet reactivity after myocardial infarction: a randomized clinical trial.

Exercise training (ET) can lower platelet reactivity in patients with cardiovascular risk factors. However, the effects of ET on platelet reactivity in higher-risk patients is unknown. The aim of this study was to evaluate the effects of ET on platelet reactivity in patients with recent myocardial infarction (MI). Ninety patients were randomly assigned 1 month post-MI to the intervention (patients submitted to a supervised ET program) or control group. All patients were on dual antiplatelet therapy (DAPT). Platelet reactivity by VerifyNow-P2Y12 (measured by P2Y12 reaction units - PRUs) test was determined at baseline and at the end of 14 ± 2 weeks of follow-up at rest (primary endpoint), and multiplate electrode aggregometry (MEA) adenosine diphosphate (ADP) and aspirin (ASPI) tests were performed immediately before and after the maximal cardiopulmonary exercise test (CPET) at the same time points (secondary endpoints). Sixty-five patients (mean age 58.9 ± 10 years; 73.8% men; 60% ST elevation MI) completed follow-up (control group, n = 31; intervention group, n = 34). At the end of the follow-up, the mean platelet reactivity was 172.8 ± 68.9 PRUs and 166.9 ± 65.1 PRUs for the control and intervention groups, respectively (p = .72). Platelet reactivity was significantly increased after the CPET compared to rest at the beginning and at the end of the 14-week follow-up (among the intervention groups) by the MEA-ADP and MEA-ASPI tests (p < .01 for all analyses). In post-MI patients on DAPT, 14 weeks of supervised ET did not reduce platelet reactivity. Moreover, platelet reactivity was increased after high-intensity exercise (ClinicalTrials.gov: NCT02958657; https://clinicaltrials.gov/ct2/show/NCT02958657).

What is the context? Platelet reactivity is reduced after exercise training in healthy individuals and patients with cardiovascular risk factors, but the effect in higher-risk patients is unknown.High-intensity exercise in untrained individuals increases platelet reactivity. The effect of dual antiplatelet therapy in inhibiting exercise-induced hyperreactivity is poorly understood.What's new?Exercise training did not reduce platelet reactivity in post-myocardial infarction patients.High-intensity exercise increased platelet reactivity in post-myocardial infarction patients on dual antiplatelet therapy.Exercise training did not attenuate the exercise-induced increase in platelet reactivity.What's the impact?The study suggests that strenuous exercise, if indicated, should be applied carefully to patients with high risk of recurrent ischemic events, even if on optimal medical therapy and after being trained.

Inflamação Coronária Avaliada pela Atenuação de Gordura Pericoronária na Tomografia Computadorizada e Elevação de Citocinas em Usuários Jovens de Esteroides Anabólicos Androgênicos / Coronary Inflammation by Computed Tomography Pericoronary Fat Attenuation and Increased Cytokines in Young Male Anabolic Androgenic Steroid Users

Resumo Fundamento O uso abusivo de esteroides anabólicos androgênicos (EAA) tem sido associado à doença arterial coronariana (DAC). A atenuação de gordura pericoronária (AGp) é um marcador de inflamação coronária, a qual exerce um papel chave no processo aterosclerótico. Objetivo Avaliar AGp e perfil inflamatório em usuários de EAA. Método Vinte indivíduos que realizavam treinamento de força, usuários de EAA (UEAA), 20 não usuários de EAA (NUEAA), e 10 indivíduos sedentários controle (SC) foram avaliados. Inflamação coronária foi avaliada por atenuação de gordura pericoronária média (AGPm) artéria coronária direita (ACD), artéria descendente anterior esquerda (ADA) e artéria circunflexa (ACX). Interleucina (IL)-1 (IL-1), IL-6, IL-10, e TNF-alfa foram avaliados por densidade ótica (DO) em um espectrofotômetro com um filtro de 450 nm. Um p<0,05 indicou significância estatística. Resultados Os UEAA apresentaram maior AGPm na ACD [-65,87 (70,51-60,70) vs. -78,07 (83,66-72,87) vs.-78,46 (85,41-71,99] unidades Hounsfield (HU), respectivamente, p<0,001) e AGPm na ADA [-71,47 (76,40-66,610 vs. -79,32 (84,37-74,59) vs. -82,52 (88,44-75,81) HU, respectivamente, p=0,006) em comparação aos NUEAA e CS. A AGPm na ACX não foi diferente entre os grupos UEAA, NUEAA e CS [-72,41 (77,17-70,37) vs. -80,13 (86,22-72,23) vs. -78,29 (80,63-72,29) HU, respectivamente, p=0,163). Em comparação aos NUEAA e aos CS, o grupo UEAA apresentaram maiores níveis de IL-1 [0,975 (0,847-1,250) vs. 0,437 (0,311-0,565) vs. 0,530 (0,402-0,780) DO, respectivamente, p=0,002), IL-6 [1,195 (0,947-1,405) vs. 0,427 (0,377-0,577) vs. 0,605 (0,332-0,950) DO, p=0,005) e IL-10 [1,145 (0,920-1,292) vs. 0,477 (0,382-0,591) vs. 0,340 (0,316-0,560) DO, p<0,001]. TNF-α não foi diferente entre os grupos UEAA, NUEAA e CS [0,520 (0,250-0,610) vs. 0,377 (0.261-0,548) vs. 0,350 (0,182-430)]. Conclusão Em comparação aos NUEAA e controles, os UEAA apresentam maior AGPm e maior perfil de citocinas inflamatórias sistêmicas, sugerindo que os EAA podem induzir aterosclerose por inflamação coronária e sistêmica.

Abstract Background Anabolic androgenic steroid (AAS) abuse has been associated with coronary artery disease (CAD). Pericoronary fat attenuation (pFA) is a marker of coronary inflammation, which is key in the atherosclerotic process. Objective To evaluate pFA and inflammatory profile in AAS users. Methods Twenty strength-trained AAS users (AASU), 20 AAS nonusers (AASNU), and 10 sedentary controls (SC) were evaluated. Coronary inflammation was evaluated by mean pericoronary fat attenuation (mPFA) in the right coronary artery (RCA), left anterior descending coronary artery (LAD), and left circumflex (LCx). Interleukin (IL)-1 (IL-1), IL-6, IL-10, and TNF-alpha were evaluated by optical density (OD) in a spectrophotometer with a 450 nm filter. P<0.05 indicated statistical significance. Results AASU had higher mPFA in the RCA (-65.87 [70.51-60.70] vs. -78.07 [83.66-72.87] vs.-78.46 [85.41-71.99] Hounsfield Units (HU), respectively, p<0.001) and mPFA in the LAD (-71.47 [76.40-66.61] vs. -79.32 [84.37-74.59] vs. -82.52 [88.44-75.81] HU, respectively, p=0.006) compared with AASNU and SC. mPFA in the LCx was not different between AASU, AASNU, and SC (-72.41 [77.17-70.37] vs. -80.13 [86.22-72.23] vs. -78.29 [80.63-72.29] HU, respectively, p=0.163). AASU compared with AASNU and SC, had higher IL-1, (0.975 [0.847-1.250] vs. 0.437 [0.311-0.565] vs. 0.530 [0.402-0.780] OD, respectively, p=0.002), IL-6 (1.195 [0.947-1.405] vs. 0.427 [0.377-0.577] vs. 0.605 [0.332-0.950] OD, p=0.005) and IL-10 (1.145 [0.920-1.292] vs. 0.477 [0.382-0.591] vs. 0.340 [0.316-0.560] OD, p<0.001). TNF-α was not different between the AASU, AASNU, and SC groups (0.520 [0.250-0.610] vs. 0.377 [0.261-0.548] vs. 0.350 [0.182-430]), respectively. Conclusion Compared with ASSNU and controls, AASU have higher mPFA and higher systemic inflammatory cytokines profile suggesting that AAS may induce coronary atherosclerosis through coronary and systemic inflammation.

Does Myocardial Injury Occur After an Acute Aerobic Exercise Session in Patients with Refractory Angina? / Ocorre Lesão Miocárdica após uma Sessão de Exercício Aeróbico Agudo em Pacientes com Angina Refratária?

BACKGROUND: It is unclear whether exercise is safe in patients with more advanced forms of coronary artery disease, such as those with refractory angina (RA). OBJECTIVE: We aimed to determine the effect of an acute aerobic exercise session (AAES) on high-sensitivity cardiac troponin T (hs-cTnT) levels in patients with RA. METHODS: This was a longitudinal, non-randomized, and non-controlled clinical study. Participants were recruited from April 2015 to January 2019. On a visual pain scale from 0 to 10, pain rated up to 3 was considered as the top level allowed to continue exercising. We assessed hs-cTnT at baseline and 3 hours after the AAES. The protocol consisted of 5 minutes of warm-up, 30 minutes of continuous aerobic exercise at heart rate corresponding to the anaerobic threshold or angina threshold obtained in the cardiopulmonary exercise testing, and 5 minutes of cooling down. P values less than 0.05 were considered statistically significant. RESULTS: Thirty-two patients with RA were included (61 ± 9 years, 59.4% male). The baseline hs-cTnT concentration was 10.9 ng/L (95% confidence interval: 9.1 to 13.0 ng/L). The hs-cTnT collected 3 hours after the AAES was 11.1 ng/L (95% confidence interval: 9.1 to 13.5 ng/L). No difference occurred in hs-cTnT before and after AAES (p = 0.657). CONCLUSIONS: A single AAES performed at the angina threshold with corresponding visual pain scale did not alter hs-cTnT in patients with RA, suggesting that no significant myocardial injury was elicited by exercising and that this exercise protocol can be considered safe.

FUNDAMENTO: Não está claro se o exercício é seguro em pacientes com formas mais avançadas de doença arterial coronariana, como aqueles com angina refratária (AR). OBJETIVO: Visamos determinar o efeito de uma sessão de exercício aeróbico agudo (SEAA) nos níveis de troponina T cardíaca de alta sensibilidade (TnT-as) em pacientes com AR. MÉTODOS: Trata-se de um estudo clínico longitudinal, não randomizado e não controlado. Os participantes foram recrutados de abril de 2015 a janeiro de 2019. Em uma escala visual de dor de 0 a 10, a dor classificada até 3 foi considerada como o nível máximo permitido para continuar o exercício. Avaliamos TnT-as na linha de base e 3 horas após a SEAA. O protocolo consistiu em 5 minutos de aquecimento, 30 minutos de exercício aeróbico contínuo na frequência cardíaca correspondente ao limiar anaeróbio ou limiar de angina obtido no teste de esforço cardiopulmonar e 5 minutos de resfriamento. Foram considerados estatisticamente significativos valores de p menores que 0,05. RESULTADOS: Foram incluídos 32 pacientes com AR (61 ± 9 anos, 59,4% do sexo masculino). A concentração basal de TnT-as foi de 10,9 ng/L (intervalo de confiança de 95%: 9,1 a 13,0 ng/L). A TnT-as coletada 3 horas após a SEAA foi de 11,1 ng/L (intervalo de confiança de 95%: 9,1 a 13,5 ng/L). Nenhuma diferença ocorreu na TnT-as antes e após a SEAA (p = 0,657). CONCLUSÕES: Uma única SEAA realizada no limiar de angina com correspondente escala visual de dor não alterou a TnT-as em pacientes com AR, sugerindo que nenhuma lesão miocárdica significativa foi provocada pelo exercício e que este protocolo de exercício pode ser considerado seguro.

Ocorre Lesão Miocárdica após uma Sessão de Exercício Aeróbico Agudo em Pacientes com Angina Refratária? / Does Myocardial Injury Occur After an Acute Aerobic Exercise Session in Patients with Refractory Angina?

Resumo Fundamento Não está claro se o exercício é seguro em pacientes com formas mais avançadas de doença arterial coronariana, como aqueles com angina refratária (AR). Objetivo Visamos determinar o efeito de uma sessão de exercício aeróbico agudo (SEAA) nos níveis de troponina T cardíaca de alta sensibilidade (TnT-as) em pacientes com AR. Métodos Trata-se de um estudo clínico longitudinal, não randomizado e não controlado. Os participantes foram recrutados de abril de 2015 a janeiro de 2019. Em uma escala visual de dor de 0 a 10, a dor classificada até 3 foi considerada como o nível máximo permitido para continuar o exercício. Avaliamos TnT-as na linha de base e 3 horas após a SEAA. O protocolo consistiu em 5 minutos de aquecimento, 30 minutos de exercício aeróbico contínuo na frequência cardíaca correspondente ao limiar anaeróbio ou limiar de angina obtido no teste de esforço cardiopulmonar e 5 minutos de resfriamento. Foram considerados estatisticamente significativos valores de p menores que 0,05. Resultados Foram incluídos 32 pacientes com AR (61 ± 9 anos, 59,4% do sexo masculino). A concentração basal de TnT-as foi de 10,9 ng/L (intervalo de confiança de 95%: 9,1 a 13,0 ng/L). A TnT-as coletada 3 horas após a SEAA foi de 11,1 ng/L (intervalo de confiança de 95%: 9,1 a 13,5 ng/L). Nenhuma diferença ocorreu na TnT-as antes e após a SEAA (p = 0,657). Conclusões Uma única SEAA realizada no limiar de angina com correspondente escala visual de dor não alterou a TnT-as em pacientes com AR, sugerindo que nenhuma lesão miocárdica significativa foi provocada pelo exercício e que este protocolo de exercício pode ser considerado seguro.

Abstract Background It is unclear whether exercise is safe in patients with more advanced forms of coronary artery disease, such as those with refractory angina (RA). Objective We aimed to determine the effect of an acute aerobic exercise session (AAES) on high-sensitivity cardiac troponin T (hs-cTnT) levels in patients with RA. Methods This was a longitudinal, non-randomized, and non-controlled clinical study. Participants were recruited from April 2015 to January 2019. On a visual pain scale from 0 to 10, pain rated up to 3 was considered as the top level allowed to continue exercising. We assessed hs-cTnT at baseline and 3 hours after the AAES. The protocol consisted of 5 minutes of warm-up, 30 minutes of continuous aerobic exercise at heart rate corresponding to the anaerobic threshold or angina threshold obtained in the cardiopulmonary exercise testing, and 5 minutes of cooling down. P values less than 0.05 were considered statistically significant. Results Thirty-two patients with RA were included (61 ± 9 years, 59.4% male). The baseline hs-cTnT concentration was 10.9 ng/L (95% confidence interval: 9.1 to 13.0 ng/L). The hs-cTnT collected 3 hours after the AAES was 11.1 ng/L (95% confidence interval: 9.1 to 13.5 ng/L). No difference occurred in hs-cTnT before and after AAES (p = 0.657). Conclusions A single AAES performed at the angina threshold with corresponding visual pain scale did not alter hs-cTnT in patients with RA, suggesting that no significant myocardial injury was elicited by exercising and that this exercise protocol can be considered safe.

Decreased Native T1 Values and Impaired Myocardial Contractility in Anabolic Steroid Users.

Anabolic androgenic steroid (AAS) abuse leads to myocardial toxicity. Human studies are conflicting about the myocardial fibrosis in AAS users. We evaluated cardiac tissue characterization, left ventricle (LV) function, and cardiac structure by cardiovascular magnetic resonance (CMR). Twenty strength-trained AAS users (AASU) aged 29±5 yr, 20 strength-trained AAS nonusers (AASNU), and 7 sedentary controls (SC) were enrolled. Native T1 mapping, late-gadolinium enhancement (LGE), extracellular volume (ECV), and myocardial strain were evaluated. AASU showed lower Native T1 values than AASNU (888±162 vs. 1020±179 ms p=0.047). Focal myocardial fibrosis was found in 2 AASU. AASU showed lower LV radial strain (30±8 vs. 38±6%, p<0.01), LV circumferential strain (-17±3 vs. -20±2%, p<0.01), and LV global longitudinal strain (-17±3 vs. -20±3%, p<0.01) than AASNU by CMR. By echocardiography, AASU demonstrated lower 4-chamber longitudinal strain than AASNU (-15±g3 vs. -18±2%, p=0.03). ECV was similar among AASU, AASNU, and SC (28±10 vs. 28±7 vs. 30±7%, p=0.93). AASU had higher LV mass index than AASNU and SC (85±14 vs. 64±8 vs. 58±5 g/m2, respectively, p<0.01). AAS abuse may be linked to decreased myocardial native T1 values, impaired myocardial contractility, and focal fibrosis. These alterations may be associated with maladaptive cardiac hypertrophy in young AAS users.

Effects of Aerobic Exercise Training on MyomiRs Expression in Cachectic and Non-Cachectic Cancer Mice.

We investigated the effects of AET on myomiRs expression in the skeletal muscle and serum of colon cachectic (CT26) and breast non-cachectic (MMTV-PyMT) cancer mice models. Colon cancer decreased microRNA-486 expression, increasing PTEN in tibialis anterior muscle (TA), decreasing the PI3K/mTOR protein pathway, body and muscle wasting, fibers' cross-sectional area and muscle dysfunction, that were not preserved by AET. In contrast, breast cancer decreased those muscle functions, but were preserved by AET. In circulation, the downregulation of microRNA-486 and -206 in colon cancer, and the downregulation of microRNA-486 and upregulation of microRNA-206 expression in breast cancer might be good cancer serum biomarkers. Since the microRNA-206 is skeletal muscle specific, their expression was increased in the TA, serum and tumor in MMTV, suggesting a communication among these three compartments. The AET prevents these effects on microRNA-206, but not on microRNA-486 in MMTV. In conclusion, cancer induced a downregulation of microRNA-486 expression in TA and serum of CT26 and MMTV mice and these effects were not prevented by AET; however, to MMTV, the trained muscle function was preserved, probably sustained by the downregulation of microRNA-206 expression. Serum microRNA-206 is a potential biomarker for colon (decreased) and breast (increased) cancer to monitor the disease evolution and the effects promoted by the AET.

Exercise training reduces sympathetic nerve activity and improves executive performance in individuals with obstructive sleep apnea.

OBJECTIVE: To investigate the effects of exercise training (ET) on muscle sympathetic nerve activity (MSNA) and executive performance during Stroop Color Word Test (SCWT) also referred to as mental stress test. METHODS: Forty-four individuals with obstructive sleep apnea (OSA) and no significant co-morbidities were randomized into 2 groups; 15 individuals completed the control period, and 18 individuals completed the ET. Mini-mental state of examination and intelligence quotient were also assessed. MSNA assessed by microneurography, heart rate by electrocardiography, blood pressure (automated oscillometric device) were measured at baseline and during 3 min of the SCWT. Peak oxygen uptake (VO2 peak) was evaluated using cardiopulmonary exercise testing. Executive performance was assessed by the total correct responses during 3 min of the SCWT. ET consisted of 3 weekly sessions of aerobic exercise, resistance exercises, and flexibility (72 sessions, achieved in 40±3.9 weeks). RESULTS: Baseline parameters were similar between groups. Heart rate, blood pressure, and MSNA responses during SCWT were similar between groups (p>0.05). The comparisons between groups showed that the changes in VO2 (4.7±0.8 vs -1.2±0.4) and apnea-hypopnea index (-7.4±3.1 vs 5.5±3.3) in the exercise-trained group were significantly greater than those observed in the control group respectively (p<0.05) after intervention. ET reduced MSNA responses (p<0.05) and significantly increased the number of correct answers (12.4%) during SCWT. The number of correct answers was unchanged in the control group (p>0.05). CONCLUSIONS: ET improves sympathetic response and executive performance during SCWT, suggesting a prominent positive impact of ET on prefrontal functioning in individuals with OSA. ClinicalTrials.gov: NCT002289625.

Effects of inspiratory muscle training combined with aerobic exercise training on neurovascular control in chronic heart failure patients.

AIMS: We tested the hypothesis that the effects of combined inspiratory muscle training and aerobic exercise training (IMT + AET) on muscle sympathetic nerve activity (MSNA) and forearm blood flow in patients with heart failure with reduced ejection fraction are more pronounced than the effects of AET alone. METHODS AND RESULTS: Patients aged 30-70 years, New York Heart Association Functional Class II-III, and left ventricular ejection fraction ≤40% were randomly assigned to four groups: IMT (n = 11), AET (n = 12), IMT + AET (n = 9), and non-training (NT; n = 10). MSNA was recorded using microneurography. Forearm blood flow was measured by venous occlusion plethysmography and inspiratory muscle strength by maximal inspiratory pressure. IMT consisted of 30 min sessions, five times a week, for 4 months. Moderate AET consisted of 60 min sessions, three times a week for 4 months. AET (-10 ± 2 bursts/min, P = 0.03) and IMT + AET (-13 ± 4 bursts/min, P = 0.007) reduced MSNA. These responses in MSNA were not different between AET and IMT + AET groups. IMT (0.22 ± 0.08 mL/min/100 mL, P = 0.03), AET (0.27 ± 0.09 mL/min/100 mL, P = 0.01), and IMT + AET (0.35 ± 0.12 mL/min/100 mL, P = 0.008) increased forearm blood flow. No differences were found between groups. AET (3 ± 1 mL/kg/min, P = 0.006) and IMT + AET (4 ± 1 mL/kg/min, P = 0.001) increased peak oxygen consumption. These responses were similar between these groups. IMT (20 ± 3 cmH2 O, P = 0.005) and IMT + AET (18 ± 3 cmH2 O, P = 0.01) increased maximal inspiratory pressure. No significant changes were observed in the NT group. CONCLUSIONS: IMT + AET causes no additive effects on neurovascular control in patients with heart failure with reduced ejection fraction compared with AET alone. These findings may be, in part, because few patients had inspiratory muscle weakness.

Association of physical activity levels and the prevalence of COVID-19-associated hospitalization.

OBJECTIVES: We compared physical activity levels before the outbreak and quarantine measures with COVID-19-associated hospitalization prevalence in surviving patients infected with SARS-CoV-2. Additionally, we investigated the association of physical activity levels with symptoms of the disease, length of hospital stay, and mechanical ventilation. DESIGN: Observational, cross-sectional. METHODS: Between June 2020 and August 2020, we invited Brazilian survivors and fully recovered patients infected with SARS-CoV-2 to respond to an online questionnaire. We shared the electronic link to the questionnaire on the internet. We collected data about clinical outcomes (symptoms, medications, hospitalization, and length of hospital stay) and cofactors, such as age, sex, ethnicity, preexisting diseases, socioeconomic and educational, and physical activity levels using the International Physical Activity Questionnaire (IPAQ short version). RESULTS: Out of 938 patients, 91 (9.7%) were hospitalized due to COVID-19. In a univariate analysis, sex, age, and BMI were all associated with hospitalizations due to COVID-19. Men had a higher prevalence of hospitalization (66.6%, p = 0.013). Patients older than 65 years, obese, and with preexisting disease had a higher prevalence of COVID-19-related hospitalizations. In a multivariate regression model, performance of at least 150 min/wk (moderate) and/or 75 min/wk (vigorous) physical activity was associated with a lower prevalence of hospitalizations after adjustment for age, sex, BMI, and preexisting diseases (PR = 0.657; p = 0.046). CONCLUSIONS: Sufficient physical activity levels were associated with a lower prevalence of COVID-19-related hospitalizations. Performing at least 150 min a week of moderate-intensity, or 75 min a week of vigorous-intensity physical activity was associated with 34.3% reduction in prevalence.

Sacubitril/valsartan versus enalapril on exercise capacity in patients with heart failure with reduced ejection fraction: A randomized, double-blind, active-controlled study.

Sacubitril/valsartan reduces mortality in patients with heart failure with reduced ejection fraction (HFrEF) when compared with enalapril. However, it is unknown the effect of both treatments on exercise capacity. We compared sacubitril/valsartan versus enalapril in patients with HFrEF based on peak oxygen consumption (VO2) and 6-minute walk test (6-MWT). METHODS: We included 52 participants with HFrEF with a left ventricular ejection fraction <40% to receive either sacubitril/valsartan (target dose of 400 mg daily) or enalapril (target dose of 40 mg daily). Peak VO2 was measured by using cardiopulmonary exercise testing. Six-minute walk test was also performed. RESULTS: At 12 weeks, the sacubitril/valsartan (mean dose 382.6 ± 57.6 mg daily) group had increased peak VO2 of 13.1% (19.35 ± 0.99 to 21.89 ± 1.04 mL/kg/min) and enalapril (mean dose 34.4 ± 9.2 mg daily) 5.6% (18.58 ± 1.19 to 19.62 ± 1.25 mL/kg/min). However, no difference was found between groups (P = .332 interaction). At 24 weeks, peak VO2 increased 13.5% (19.35 ± 0.99 to 21.96 ± 0.98 mL/kg/min) and 12.0% (18.58 ± 1.19 to 20.82 ± 1.18 mL/kg/min) in sacubitril/valsartan (mean dose 400 ± 0 mg daily) and enalapril (mean dose 32.7 ± 11.0 mg daily), respectively. However, no differences were found between groups (P= .332 interaction). At 12 weeks, 6-MWT increased in both groups (sacubitril/valsartan: 459 ± 18 to 488 ± 17 meters [6.3%] and enalapril: 443 ± 22 to 477 ± 21 meters [7.7%]). At 24 weeks, sacubitril/valsartan increased 18.3% from baseline (543 ± 26 meters) and enalapril decreased slightly to 6.8% (473 ± 31 meters), but no differences existed between groups (P= .257 interaction). CONCLUSIONS: Compared to enalapril, sacubitril/valsartan did not substantially improve peak VO2 or 6-MWT after 12 or 24 weeks in participants with HFrEF. (NEPRIExTol-HF Trial, ClinicalTrials.gov number, NCT03190304).

Aerobic exercise and inspiratory muscle training increase functional capacity in patients with univentricular physiology after Fontan operation: A randomized controlled trial.

BACKGROUND: The effect of exercise training and its mechanisms on the functional capacity improvement in Fontan patients (FP) are virtually unknown. This trial evaluated four-month aerobic exercise training and inspiratory muscle training on functional capacity, pulmonary function, and autonomic control in patients after Fontan operation. METHODS: A randomized controlled clinical trial with 42 FP aged 12 to 30 years and, at least, five years of Fontan completion. Twenty-seven were referred to a four-months supervised and personalized aerobic exercise training (AET) or an inspiratory muscle training (IMT). A group of non-exercise (NET) was used as control. The effects of the exercise training in peak VO2; pulmonary volumes and capacities, maximal inspiratory pressure (MIP); muscle sympathetic nerve activity (MSNA); forearm blood flow (FBF); handgrip strength and cross-sectional area of the thigh were analyzed. RESULTS: The AET decreased MSNA (p = 0.042), increased FBF (p = 0.012) and handgrip strength (p = 0.017). No significant changes in autonomic control were found in IMT and NET groups. Both AET and IMT increased peak VO2, but the increase was higher in the AET group compared to IMT (23% vs. 9%). No difference was found in the NET group. IMT group showed a 58% increase in MIP (p = 0.008) in forced vital capacity (p = 0.011) and forced expiratory volume in the first second (p = 0.011). No difference in pulmonary function was found in the AET group. CONCLUSIONS: Both aerobic exercise and inspiratory muscle training improved functional capacity. The AET group developed autonomic control, and handgrip strength, and the IMT increased inspiratory muscle strength and spirometry. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02283255.

Exercise training reduces sympathetic nerve activity and improves executive performance in individuals with obstructive sleep apnea

OBJECTIVE: To investigate the effects of exercise training (ET) on muscle sympathetic nerve activity (MSNA) and executive performance during Stroop Color Word Test (SCWT) also referred to as mental stress test. METHODS: Forty-four individuals with obstructive sleep apnea (OSA) and no significant co-morbidities were randomized into 2 groups; 15 individuals completed the control period, and 18 individuals completed the ET. Mini-mental state of examination and intelligence quotient were also assessed. MSNA assessed by microneurography, heart rate by electrocardiography, blood pressure (automated oscillometric device) were measured at baseline and during 3 min of the SCWT. Peak oxygen uptake (VO2 peak) was evaluated using cardiopulmonary exercise testing. Executive performance was assessed by the total correct responses during 3 min of the SCWT. ET consisted of 3 weekly sessions of aerobic exercise, resistance exercises, and flexibility (72 sessions, achieved in 40±3.9 weeks). RESULTS: Baseline parameters were similar between groups. Heart rate, blood pressure, and MSNA responses during SCWT were similar between groups (p>0.05). The comparisons between groups showed that the changes in VO2 (4.7±0.8 vs -1.2±0.4) and apnea-hypopnea index (-7.4±3.1 vs 5.5±3.3) in the exercise-trained group were significantly greater than those observed in the control group respectively (p<0.05) after intervention. ET reduced MSNA responses (p<0.05) and significantly increased the number of correct answers (12.4%) during SCWT. The number of correct answers was unchanged in the control group (p>0.05). CONCLUSIONS: ET improves sympathetic response and executive performance during SCWT, suggesting a prominent positive impact of ET on prefrontal functioning in individuals with OSA. ClinicalTrials.gov: NCT002289625.

Muscle mass, muscle strength, and functional capacity in patients with heart failure of Chagas disease and other aetiologies.

AIMS: Patients with Chagas disease and heart failure (HF) have a poor prognosis similar to that of patients with ischaemic or dilated cardiomyopathy. However, the impact of body composition and muscle strength changes in these aetiologies is still unknown. We aimed to evaluate these parameters across aetiologies in two distinct cohort studies [TESTOsterone-Heart Failure trial (TESTO-HF; Brazil) and Studies Investigating Co-morbidities Aggravating Heart Failure (SICA-HF; Germany)]. METHODS AND RESULTS: A total of 64 male patients with left ventricular ejection fraction ≤40% were matched for body mass index and New York Heart Association class, including 22 patients with Chagas disease (TESTO-HF; Brazil), and 20 patients with dilated cardiomyopathy and 22 patients with ischaemic heart disease (SICA-HF; Germany). Lean body mass (LBM), appendicular lean mass (ALM), and fat mass were assessed by dual energy X-ray absorptiometry. Sarcopenia was defined as ALM divided by height in metres squared <7.0 kg/m2 (ALM/height2 ) and handgrip strength cut-off for men according to the European Working Group on Sarcopenia in Older People. All patients performed maximal cardiopulmonary exercise testing. Forearm blood flow (FBF) was measured by venous occlusion plethysmography. Chagasic and ischaemic patients had lower total fat mass (16.3 ± 8.1 vs. 19.3 ± 8.0 vs. 27.6 ± 9.4 kg; P < 0.05) and reduced peak oxygen consumption (VO2 ) (1.17 ± 0.36 vs. 1.15 ± 0.36 vs. 1.50 ± 0.45 L/min; P < 0.05) than patients with dilated cardiomyopathy, respectively. Chagasic patients showed a trend towards decreased LBM when compared with ischaemic patients (48.3 ± 7.6 vs. 54.2 ± 6.3 kg; P = 0.09). Chagasic patients showed lower handgrip strength (27 ± 8 vs. 37 ± 11 vs. 36 ± 14 kg; P < 0.05) and FBF (1.84 ± 0.54 vs. 2.75 ± 0.76 vs. 3.42 ± 1.21 mL/min/100 mL; P < 0.01) than ischaemic and dilated cardiomyopathy patients, respectively. There was no statistical difference in the distribution of sarcopenia between groups (P = 0.87). In addition, FBF correlated positively with LBM (r = 0.31; P = 0.012), ALM (r = 0.25; P = 0.046), and handgrip strength (r = 0.36; P = 0.004). In a logistic regression model using peak VO2 as the dependent variable, haemoglobin (odds ratio, 1.506; 95% confidence interval, 1.043-2.177; P = 0.029) and ALM (odds ratio, 1.179; 95% confidence interval, 1.011-1.374; P = 0.035) were independent predictors for peak VO2 adjusted by age, left ventricular ejection fraction, New York Heart Association, creatinine, and FBF. CONCLUSIONS: Patients with Chagas disease and HF have decreased fat mass and exhibit reduced peripheral blood flow and impaired muscle strength compared with ischaemic HF patients. In addition, patients with Chagas disease and HF show a tendency to have greater reduction in total LBM, with ALM remaining an independent predictor of reduced functional capacity in these patients. The percentage of patients affected by sarcopenia was equal between groups.

Android to gynoid fat ratio and its association with functional capacity in male patients with heart failure.

AIMS: We studied the association between android (A) to gynoid (G) fat ratio and functional capacity (peak VO2 ) in male patients with heart failure with reduced ejection fraction (HFrEF). METHODS AND RESULTS: We enrolled 118 male patients with HFrEF with left ventricular ejection fraction (LVEF) <40%. Body composition (by using dual x-ray absorptiometry) and peak VO2 (by cardiopulmonary exercise testing) were measured. Sarcopenic obesity was defined according to the Foundation for the National Institutes of Health criteria (FNIH). Blood sample for metabolic and hormonal parameters were measured. Fifteen patients (12.7%) showed sarcopenic obesity (body mass index > 25 kg/m2 with FNIH index < 0.789). The median A/G ratio was 0.55. A/G ratio > 0.55 was detected in 60 patients. Relative peak VO2 was lower in patients with A/G ratio > 0.55 than in patients with A/G ratio <0.55 (18.7 ± 5.3 vs. 22.5 ± 6.1 mL/kg/min, P < 0.001). Logistic regression analysis showed A/G ratio >0.55 to be independently associated with reduced peak VO2 adjusted for age, body mass index, LVEF, presence of sarcopenia, anabolic hormones, and haemoglobin (odds ratio 3.895, 95% confidence interval 1.030-14.730, P = 0.045). CONCLUSIONS: Body fat distribution, particularly android and gynoid fat composition, together with other cofactors, might have an important adverse role on functional capacity in male patients with HFrEF. Future studies are needed to address possible mechanisms involved in this relationship.