Differential impacts of body composition on oxygen kinetics and exercise tolerance of HFrEF and HFpEF patients.

This study aims to (1) compare the kinetics of pulmonary oxygen uptake (VO2p), skeletal muscle deoxygenation ([HHb]), and microvascular O2 delivery (QO2mv) between heart failure (HF) patients with reduced ejection fraction (HFrEF) and those with preserved ejection fraction (HFpEF), and (2) explore the correlation between body composition, kinetic parameters, and exercise performance. Twenty-one patients (10 HFpEF and 11 HFrEF) underwent cardiopulmonary exercise testing to assess VO2 kinetics, with near-infrared spectroscopy (NIRS) employed to measure [HHb]. Microvascular O2 delivery (QO2mv) was calculated using the Fick principle. Dual-energy X-ray absorptiometry (DEXA) was performed to evaluate body composition. HFrEF patients exhibited significantly slower VO2 kinetics (time constant [t]: 63 ± 10.8 s vs. 45.4 ± 7.9 s; P < 0.05) and quicker [HHb] response (t: 12.4 ± 9.9 s vs. 25 ± 11.6 s; P < 0.05). Microvascular O2 delivery (QO2mv) was higher in HFrEF patients (3.6 ± 1.2 vs. 1.7 ± 0.8; P < 0.05), who also experienced shorter time to exercise intolerance (281.6 ± 84 s vs. 405.3 ± 96 s; P < 0.05). Correlation analyses revealed a significant negative relationship between time to exercise and both QO2mv (ρ= -0.51; P < 0.05) and VO2 kinetics (ρ= -0.63). Body adiposity was negatively correlated with [HHb] amplitude (ρ= -0.78) and peak VO2 (ρ= -0.54), while a positive correlation was observed between lean muscle percentage, [HHb] amplitude, and tau (ρ= 0.74 and 0.57; P < 0.05), respectively. HFrEF patients demonstrate more severely impaired VO2p kinetics, skeletal muscle deoxygenation, and microvascular O2 delivery compared to HFpEF patients, indicating compromised peripheral function. Additionally, increased adiposity and reduced lean mass are linked to decreased oxygen diffusion capacity and impaired oxygen uptake kinetics in HFrEF patients.

Comparable Ventilatory Inefficiency at Maximal and Submaximal Performance in COPD vs. CHF subjects: An Innovative Approach. / Ineficiência Ventilatória Comparável no Desempenho Máximo e Submáximo em Indivíduos com DPOC e ICC: Uma Abordagem Inovadora.

BACKGROUND: Currently, excess ventilation has been grounded under the relationship between minute-ventilation/carbon dioxide output ( V ˙ E - V ˙ CO 2 ). Alternatively, a new approach for ventilatory efficiency ( η E V ˙ ) has been published. OBJECTIVE: Our main hypothesis is that comparatively low levels of η E V ˙ between chronic heart failure (CHF) and chronic obstructive pulmonary disease (COPD) are attainable for a similar level of maximum and submaximal aerobic performance, conversely to long-established methods ( V ˙ E - V ˙ CO 2 slope and intercept). METHODS: Both groups performed lung function tests, echocardiography, and cardiopulmonary exercise testing. The significance level adopted in the statistical analysis was 5%. Thus, nineteen COPD and nineteen CHF-eligible subjects completed the study. With the aim of contrasting full values of V ˙ E - V ˙ CO 2 and η V ˙ E for the exercise period (100%), correlations were made with smaller fractions, such as 90% and 75% of the maximum values. RESULTS: The two groups attained matched characteristics for age (62±6 vs. 59±9 yrs, p>.05), sex (10/9 vs. 14/5, p>0.05), BMI (26±4 vs. 27±3 Kg m2, p>0.05), and peak V ˙ O 2 (72±19 vs. 74±20 %pred, p>0.05), respectively. The V ˙ E - V ˙ CO 2 slope and intercept were significantly different for COPD and CHF (27.2±1.4 vs. 33.1±5.7 and 5.3±1.9 vs. 1.7±3.6, p<0.05 for both), but η V ˙ E average values were similar between-groups (10.2±3.4 vs. 10.9±2.3%, p=0.462). The correlations between 100% of the exercise period with 90% and 75% of it were stronger for η V ˙ E (r>0.850 for both). CONCLUSION: The η V ˙ E is a valuable method for comparison between cardiopulmonary diseases, with so far distinct physiopathological mechanisms, including ventilatory constraints in COPD.

FUNDAMENTO: Atualmente, o excesso de ventilação tem sido fundamentado na relação entre ventilação-minuto/produção de dióxido de carbono ( V ˙ E − V ˙ CO 2 ). Alternativamente, uma nova abordagem para eficiência ventilatória ( η E V ˙ ) tem sido publicada. OBJETIVO: Nossa hipótese principal é que níveis comparativamente baixos de η E V ˙ entre insuficiência cardíaca crônica (ICC) e doença pulmonar obstrutiva crônica (DPOC) são atingíveis para um nível semelhante de desempenho aeróbico máximo e submáximo, inversamente aos métodos estabelecidos há muito tempo (inclinação V ˙ E − V ˙ CO 2 e intercepto). MÉTODOS: Ambos os grupos realizaram testes de função pulmonar, ecocardiografia e teste de exercício cardiopulmonar. O nível de significância adotada na análise estatística foi 5%. Assim, dezenove indivíduos elegíveis para DPOC e dezenove indivíduos elegíveis para ICC completaram o estudo. Com o objetivo de contrastar valores completos de V ˙ E − V ˙ CO 2 e η E V ˙ para o período de exercício (100%), correlações foram feitas com frações menores, como 90% e 75% dos valores máximos. RESULTADOS: Os dois grupos tiveram características correspondentes para a idade (62±6 vs 59±9 anos, p>.05), sexo (10/9 vs 14/5, p>0,05), IMC (26±4 vs 27±3 Kg m2, p>0,05), e pico V ˙ O 2 (72±19 vs 74±20 % pred, p>0,05), respectivamente. A inclinação V ˙ E − V ˙ CO 2 e intercepto foram significativamente diferentes para DPOC e ICC (207,2±1,4 vs 33,1±5,7 e 5,3±1,9 vs 1,7±3,6, p<0,05 para ambas), mas os valores médios da η E V ˙ foram semelhantes entre os grupos (10,2±3,4 vs 10,9±2,3%, p=0,462). As correlações entre 100% do período do exercício com 90% e 75% dele foram mais fortes para η E V ˙ (r>0,850 para ambos). CONCLUSÃO: A η E V ˙ é um método valioso para comparação entre doenças cardiopulmonares, com mecanismos fisiopatológicos até agora distintos, incluindo restrições ventilatórias na DPOC.

Ineficiência Ventilatória Comparável no Desempenho Máximo e Submáximo em Indivíduos com DPOC e ICC: Uma Abordagem Inovadora / Comparable Ventilatory Inefficiency at Maximal and Submaximal Performance in COPD vs. CHF subjects: An Innovative Approach

Resumo Fundamento: Atualmente, o excesso de ventilação tem sido fundamentado na relação entre ventilação-minuto/produção de dióxido de carbono ( V ˙ E − V ˙ CO 2). Alternativamente, uma nova abordagem para eficiência ventilatória ( η E V ˙) tem sido publicada. Objetivo: Nossa hipótese principal é que níveis comparativamente baixos de η E V ˙ entre insuficiência cardíaca crônica (ICC) e doença pulmonar obstrutiva crônica (DPOC) são atingíveis para um nível semelhante de desempenho aeróbico máximo e submáximo, inversamente aos métodos estabelecidos há muito tempo (inclinação V ˙ E − V ˙ CO 2 e intercepto). Métodos: Ambos os grupos realizaram testes de função pulmonar, ecocardiografia e teste de exercício cardiopulmonar. O nível de significância adotada na análise estatística foi 5%. Assim, dezenove indivíduos elegíveis para DPOC e dezenove indivíduos elegíveis para ICC completaram o estudo. Com o objetivo de contrastar valores completos de V ˙ E − V ˙ CO 2 e η E V ˙ para o período de exercício (100%), correlações foram feitas com frações menores, como 90% e 75% dos valores máximos. Resultados: Os dois grupos tiveram características correspondentes para a idade (62±6 vs 59±9 anos, p>.05), sexo (10/9 vs 14/5, p>0,05), IMC (26±4 vs 27±3 Kg m2, p>0,05), e pico V ˙ O 2 (72±19 vs 74±20 % pred, p>0,05), respectivamente. A inclinação V ˙ E − V ˙ CO 2 e intercepto foram significativamente diferentes para DPOC e ICC (207,2±1,4 vs 33,1±5,7 e 5,3±1,9 vs 1,7±3,6, p<0,05 para ambas), mas os valores médios da η E V ˙ foram semelhantes entre os grupos (10,2±3,4 vs 10,9±2,3%, p=0,462). As correlações entre 100% do período do exercício com 90% e 75% dele foram mais fortes para η E V ˙ (r>0,850 para ambos). Conclusão: A η E V ˙ é um método valioso para comparação entre doenças cardiopulmonares, com mecanismos fisiopatológicos até agora distintos, incluindo restrições ventilatórias na DPOC.

Abstract Background: Currently, excess ventilation has been grounded under the relationship between minute-ventilation/carbon dioxide output ( V ˙ E − V ˙ CO 2). Alternatively, a new approach for ventilatory efficiency ( η E V ˙) has been published. Objective: Our main hypothesis is that comparatively low levels of η E V ˙ between chronic heart failure (CHF) and chronic obstructive pulmonary disease (COPD) are attainable for a similar level of maximum and submaximal aerobic performance, conversely to long-established methods ( V ˙ E − V ˙ CO 2 slope and intercept). Methods: Both groups performed lung function tests, echocardiography, and cardiopulmonary exercise testing. The significance level adopted in the statistical analysis was 5%. Thus, nineteen COPD and nineteen CHF-eligible subjects completed the study. With the aim of contrasting full values of V ˙ E − V ˙ CO 2 and η V ˙ E for the exercise period (100%), correlations were made with smaller fractions, such as 90% and 75% of the maximum values. Results: The two groups attained matched characteristics for age (62±6 vs. 59±9 yrs, p>.05), sex (10/9 vs. 14/5, p>0.05), BMI (26±4 vs. 27±3 Kg m2, p>0.05), and peak V ˙ O 2 (72±19 vs. 74±20 %pred, p>0.05), respectively. The V ˙ E − V ˙ CO 2 slope and intercept were significantly different for COPD and CHF (27.2±1.4 vs. 33.1±5.7 and 5.3±1.9 vs. 1.7±3.6, p<0.05 for both), but η V ˙ E average values were similar between-groups (10.2±3.4 vs. 10.9±2.3%, p=0.462). The correlations between 100% of the exercise period with 90% and 75% of it were stronger for η V ˙ E (r>0.850 for both). Conclusion: The η V ˙ E is a valuable method for comparison between cardiopulmonary diseases, with so far distinct physiopathological mechanisms, including ventilatory constraints in COPD.

Early Neuromuscular Electrical Stimulation Preserves Muscle Size and Quality and Maintains Systemic Levels of Signaling Mediators of Muscle Growth and Inflammation in Patients with Traumatic Brain Injury: A Randomized Clinical Trial.

Objective: To investigate the effects of an early neuromuscular electrical stimulation (NMES) protocol on muscle quality and size as well as signaling mediators of muscle growth and systemic inflammation in patients with traumatic brain injury (TBI). Design: Two-arm, single-blinded, parallel-group, randomized, controlled trial with a blinded assessment. Setting. Trauma intensive care unit at a university hospital. Participants. Forty consecutive patients on mechanical ventilation (MV) secondary to TBI were prospectively recruited within the first 24 hours following admission. Interventions. The intervention group (NMES; n = 20) received a daily session of NMES on the rectus femoris muscle for five consecutive days (55 min/each session). The control group (n = 20) received usual care. Main Outcome Measures. Muscle echogenicity and thickness were evaluated by ultrasonography. A daily blood sample was collected to assess circulating levels of insulin-like growth factor I (IGF-I), inflammatory cytokines, and matrix metalloproteinases (MMP). Results: Both groups were similar at baseline. A smaller change in muscle echogenicity and thickness (difference between Day 1 and Day 7) was found in the control group compared to the NMES group (29.9 ± 2.1 vs. 3.0 ± 1.2, p < 0.001; -0.79 ± 0.12 vs. -0.01 ± 0.06, p < 0.001, respectively). Circulating levels of IGF-I, pro-inflammatory cytokines (IFN-y), and MMP were similar between groups. Conclusion: An early NMES protocol can preserve muscle size and quality and maintain systemic levels of signaling mediators of muscle growth and inflammation in patients with TBI. This trial is registered with https://www.ensaiosclinicos.gov.br under number RBR-2db.

Inspiratory muscle training on quality of life in individuals with spinal cord injury: A systematic review and meta-analysis.

STUDY DESIGN: Systematic review and meta-analysis. OBJECTIVES: The objective was to summarize the effectiveness of Inspiratory Muscle Training (IMT) on the quality of life in individuals with Spinal Cord Injury (SCI). METHODS: An online systematic literature search was conducted in the following databases: PubMed/MEDLINE, PubMed CENTRAL, EMBASE, ISI Web of Science, SciELO, CINAHL/SPORTDiscus, and PsycINFO. Randomized and non-randomized clinical studies investigating the effectiveness of IMT in quality of life were included in the present study. The results used the mean difference and 95% confidence interval for maximal inspiratory pressure (MIP), forced expiratory volume in 1 s (FEV1), maximal expiratory pressure (MEP), and the standardized mean differences for the quality of life and maximum ventilation volume. RESULTS: The search found 232 papers, and after the screening, four studies met the inclusion criteria and were included in the meta-analytical procedures (n = 150 participants). No changes were demonstrated in the quality of life domains (general health, physical function, mental health, vitality, social function, emotional problem, and pain) after IMT. The IMT provided a considerable effect over the MIP but not on FEV1 and MEP. Conversely, it was not able to provide changes in any of the quality of life domains. None of the included studies evaluated the IMT effects on the expiratory muscle maximal expiratory pressure. CONCLUSION: Evidence from studies shows that inspiratory muscle training improves the MIP; however, this effect does not seem to translate to any change in the quality of life or respiratory function outcomes in individuals with SCI.

Short-term physical exercise controls age-related hyperinsulinemia and improves hepatic metabolism in aged rodents.

PURPOSE: Aging is associated with changes in glucose homeostasis related to both decreased insulin secretion and/or impaired insulin action, contributing to the high prevalence of type 2 diabetes (T2D) in the elderly population. Additionally, studies are showing that chronically high levels of circulating insulin can also lead to insulin resistance. In contrast, physical exercise has been a strategy used to improve insulin sensitivity and metabolic health. However, the molecular alterations resulting from the effects of physical exercise in the liver on age-related hyperinsulinemia conditions are not yet fully established. This study aimed to investigate the effects of 7 days of aerobic exercise on hepatic metabolism in aged hyperinsulinemic rats (i.e., Wistar and F344) and in Slc2a4+/- mice (hyperglycemic and hyperinsulinemic mice). RESULTS: Both aged models showed alterations in insulin and glucose tolerance, which were associated with essential changes in hepatic fat metabolism (lipogenesis, gluconeogenesis, and inflammation). In contrast, 7 days of physical exercise was efficient in improving whole-body glucose and insulin sensitivity, and hepatic metabolism. The Slc2a4+/- mice presented significant metabolic impairments (insulin resistance and hepatic fat accumulation) that were improved by short-term exercise training. In this scenario, high circulating insulin may be an important contributor to age-related insulin resistance and hepatic disarrangements in some specific conditions. CONCLUSION: In conclusion, our data demonstrated that short-term aerobic exercise was able to control mechanisms related to hepatic fat accumulation and insulin sensitivity in aged rodents. These effects could contribute to late-life metabolic health and prevent the development/progression of age-related T2D.

Acute hemodynamic responses from low-load resistance exercise with blood flow restriction in young and older individuals: A systematic review and meta-analysis of cross-over trials.

OBJECTIVE: To summarize the existing evidence on the acute response of low-load (LL) resistance exercise (RE) with blood flow restriction (BFR) on hemodynamic parameters. DATA SOURCES: MEDLINE (via PubMed), EMBASE (via Scopus), SPORTDiscus, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, Web of Science and MedRxiv databases were searched from inception to February 2022. REVIEW METHODS: Cross-over trials investigating the acute effect of LLRE + BFR versus passive (no exercise) and active control methods (LLRE or HLRE) on heart rate (HR), systolic (SBP), diastolic (DBP) and mean (MBP) blood pressure responses. RESULTS: The quality of the studies was assessed using the PEDro scale, risk of bias using the RoB 2.0 tool for cross-over trials and certainty of the evidence using the GRADE method. A total of 15 randomized cross-over studies with 466 participants were eligible for analyses. Our data showed that LLRE + BFR increases all hemodynamic parameters compared to passive control, but not compared to conventional resistance exercise. Subgroup analysis did not demonstrate any differences between LLRE + BFR and low- (LL) or high-load (HL) resistance exercise protocols. Studies including younger volunteers presented higher chronotropic responses (HR) than those with older volunteers. CONCLUSIONS: Despite causing notable hemodynamic responses compared to no exercise, the short-term LL resistance exercise with BFR modulates all hemodynamic parameters HR, SBP, DBP and MBP, similarly to a conventional resistance exercise protocol, whether at low or high-intensity. The chronotropic response is slightly higher in younger healthy individuals despite the similarity regarding pressure parameters.

Muscle-Skeletal Abnormalities and Muscle Oxygenation during Isokinetic Strength Exercise in Heart Failure with Preserved Ejection Fraction Phenotype: A Cross-Sectional Study.

Exercise intolerance, a hallmark of patients with heart failure (HF), is associated with muscle weakness. However, its causative microcirculatory and muscle characteristics among those with preserved or reduced ejection fraction (HFpEF or HFrEF) phenotype is unclear. The musculoskeletal abnormalities that could result in impaired peripheral microcirculation are sarcopenia and muscle strength reduction in HF, implying lowered oxidative capacity and perfusion affect transport and oxygen utilization during exercise, an essential task from the microvascular muscle function. Besides that, skeletal muscle microcirculatory abnormalities have also been associated with exercise intolerance in HF patients who also present skeletal muscle myopathy. This cross-sectional study aimed to compare the muscle microcirculation dynamics via near-infrared spectroscopy (NIRS) response during an isokinetic muscle strength test and ultrasound-derived parameters (echo intensity was rectus femoris muscle, while the muscle thickness parameter was measured on rectus femoris and quadriceps femoris) in heart failure patients with HFpEF and HFrEF phenotypes and different functional severities (Weber Class A, B, and C). Twenty-eight aged-matched patients with HFpEF (n = 16) and HFrEF (n = 12) were assessed. We found phenotype differences among those with Weber C severity, with HFrEF patients reaching lower oxyhemoglobin (O2Hb, µM) (-10.9 ± 3.8 vs. -23.7 ± 5.7, p = 0.029) during exercise, while HFpEF reached lower O2Hb during the recovery period (-3.0 ± 3.4 vs. 5.9 ± 2.8, p = 0.007). HFpEF with Weber Class C also presented a higher echo intensity than HFrEF patients (29.7 ± 8.4 vs. 15.1 ± 6.8, p = 0.017) among the ultrasound-derived variables. Our preliminary study revealed more pronounced impairments in local microcirculatory dynamics in HFpEF vs. HFrEF patients during a muscle strength exercise, combined with muscle-skeletal abnormalities detected via ultrasound imaging, which may help explain the commonly observed exercise intolerance in HFpEF patients.

Moderate-intensity exercise with blood flow restriction on cardiopulmonary kinetics and efficiency during a subsequent high-intensity exercise in young women: A cross-sectional study.

ABSTRACT: Blood flow restriction (BFR) training applied prior to a subsequent exercise has been used as a method to induce changes in oxygen uptake pulmonary kinetics (O2P) and exercise performance. However, the effects of a moderate-intensity training associated with BFR on a subsequent high-intensity exercise on O2P and cardiac output (QT) kinetics, exercise tolerance, and efficiency remain unknown.This prospective physiologic study was performed at the Exercise Physiology Lab, University of Brasilia. Ten healthy females (mean ±â€ŠSD values: age = 21.3 ±â€Š2.2 years; height = 1.6 ±â€Š0.07 m, and weight = 55.6 ±â€Š8.8 kg) underwent moderate-intensity training associated with or without BFR for 6 minutes prior to a maximal high-intensity exercise bout. O2P, heart rate, and QT kinetics and gross efficiency were obtained during the high-intensity constant workload exercise test.No differences were observed in O2P, heart rate, and QT kinetics in the subsequent high-intensity exercise following BFR training. However, exercise tolerance and gross efficiency were significantly greater after BFR (220 ±â€Š45 vs 136 ±â€Š30 seconds; P < .05, and 32.8 ±â€Š6.3 vs 27.1 ±â€Š5.4%; P < .05, respectively), which also resulted in lower oxygen cost (1382 ±â€Š227 vs 1695 ±â€Š305 mL min-1).We concluded that moderate-intensity BFR training implemented prior to a high-intensity protocol did not accelerate subsequent O2P and QT kinetics, but it has the potential to improve both exercise tolerance and work efficiency at high workloads.

Maximal Dynamic Inspiratory Pressure Evaluation in Heart Failure: A Comprehensive Reliability and Agreement Study.

OBJECTIVE: The purpose of this study was to analyze the reliability (interrater and intrarater) and agreement (repeatability and reproducibility) properties of tapered flow resistive loading (TFRL) measures in patients with heart failure (HF). METHODS: For this cross-sectional study, participants were recruited from the cardiopulmonary rehabilitation program at the University of Brasilia from July 2015 to July 2016. All patients participated in the study, and 10 were randomly chosen for intrarater and interrater reliability testing. The 124 participants with HF (75% men) were 57.6 (SD = 1.81) years old and had a mean left ventricular ejection fraction of 38.9% (SD = 15%) and a peak oxygen consumption of 13.05 (SD = 5.3) mL·kg·min-1. The main outcome measures were the maximal inspiratory pressure (MIP) measured with a standard manovacuometer (SM) and the MIP and maximal dynamic inspiratory pressure (S-Index) obtained with TFRL. The S-Index reliability (interrater and intrarater) was examined by 2 evaluators, the S-Index repeatability was examined with 10 repetitions, and the reproducibility of the MIP and S-Index was measured with SM and TFRL, respectively. RESULTS: The reliability analysis revealed high S-Index interrater and intrarater reliability values (intraclass correlation coefficients [ICCs] of 0.89 [95% CI = 0.58-0.98] and 0.97 [95% CI = 0.89-0.99], respectively). Repeatability analyses revealed that 8 maneuvers were required to reach the maximum S-Index in 75.81% (95% CI = 68.27-83.34) of the population. The reproducibility of TFRL measures (S-Index = 68.8 [SD = 32.8] cm H2O; MIP = 66 [SD = 32.3] cm H2O) was slightly lower than that of the SM measurement (MIP = 70.1 [SD = 35.9] cm H2O). CONCLUSIONS: The TFRL device provided a reliable intrarater and interrater S-Index measure in patients with HF and had acceptable repeatability, requiring 8 maneuvers to produce a stable S-Index measure. The reproducibilities of the S-Index, MIP obtained with SM, and MIP obtained with TRFL were similar. IMPACT: TRFL is a feasible method to assess both MIP and the S-index as measures of inspiratory muscle strength in patients with HF and can be used for inspiratory muscle training, making the combined testing and training capabilities important in both clinical research and the management of patients with HF.

Neuromuscular electrical stimulation combined with exercise decreases duration of mechanical ventilation in ICU patients: A randomized controlled trial.

BACKGROUND: Early mobilization can be employed to minimize the duration of intensive care. However, a protocol combining neuromuscular electrical stimulation (NMES) with early mobilization has not yet been tested in ICU patients. Our aim was to assess the efficacy of NMES, exercise (EX), and combined therapy (NMES + EX) on duration of mechanical ventilation (MV) in critically ill patients. METHODS: The participants in this randomized double-blind trial were prospectively recruited within 24 hours following admission to the intensive care unit of a tertiary hospital. Eligible patients had 18 years of age or older; MV for less than 72 hours; and no known neuromuscular disease. Computer-generated permuted block randomization was used to assign patients to NMES, EX, NMES + EX, or standard care (control group). The main endpoint was duration of MV. Clinical characteristics were also evaluated and intention to treat analysis was employed. RESULTS: One hundred forty-four patients were assessed for eligibility to participate in the trial, 51 of whom were enrolled and randomly allocated into four groups: 11 patients in the NMES group, 13 in the EX group, 12 in the NMES + EX group, and 15 in the control group (CG). Duration of MV (days) was significantly shorter in the combined therapy (5.7 ± 1.1) and NMEN (9.0 ± 7.0) groups in comparison to CG (14.8 ± 5.4). CONCLUSIONS: NMES + EX consisting of NMES and active EXs was well tolerated and resulted in shorter duration of MV in comparison to standard care or isolated therapy (NMES or EX alone).

Current insights of inspiratory muscle training on the cardiovascular system: a systematic review with meta-analysis.

Background: Cardiorespiratory limitation is a common hallmark of cardiovascular disease which is a key component of pharmacological and exercise treatments. More recently, inspiratory muscle training (IMT) is becoming an effective complementary treatment with positive effects on muscle strength and exercise capacity. We assessed the effectiveness of IMT on the cardiovascular system through autonomic function modulation via heart rate variability and arterial blood pressure. Methods: Randomized controlled trials (RCTs) were identified from searches of The Cochrane Library, MEDLINE and EMBASE to November 2018. Citations, conference proceedings and previous reviews were included without population restriction, comparing IMT intervention to no treatment, placebo or active control. Results: We identified 10 RCTs involving 267 subjects (mean age range 51-71 years). IMT programs targeted maximum inspiratory pressure (MIP) and cardiovascular outcomes, using low (n=6) and moderate to high intensity (n=4) protocols, but the protocols varied considerably (duration: 1-12 weeks, frequency: 3-14 times/week, time: 10-30 mins). An overall increase of the MIP (cmH2O) was observed (-27.57 95% CI -18.48, -37.45, I 2=64%), according to weighted mean difference (95%CI), and was accompanied by a reduction of the low to high frequency ratio (-0.72 95% CI-1.40, -0.05, I 2=50%). In a subgroup analysis, low- and moderate-intensity IMT treatment was associated with a reduction of the heart rate (HR) (-7.59 95% CI -13.96, -1.22 bpm, I 2=0%) and diastolic blood pressure (DBP) (-8.29 [-11.64, -4.94 mmHg], I 2=0%), respectively. Conclusion: IMT is an effective treatment for inspiratory muscle weakness in several populations and could be considered as a complementary treatment to improve the cardiovascular system, mainly HR and DBP. Further research is required to better understand the above findings.

Alteraciones de la cognición social en síndromes de alto riesgo en psicosis / Social cognitive impairment in clinical high risk for psychos

Resumen La esquizofrenia es una enfermedad crónica, severa y que afecta aproximadamente al 1% de la población mundial. Pacientes con esta enfermedad presentan severos déficits en la cognición social (DCS). Estos déficits han sido observados en pacientes de primer episodio y familiares de primer grado. Los DCS determinan el pronóstico a largo plazo en esta enfermedad y son susceptibles de rehabilitación si es que se detectan precozmente. Solo recientemente se han caracterizado los déficits de la cognición social en sujetos de alto riesgo de desarrollar psicosis crónica. Estos sujetos presentan una oportunidad única para modificar la inserción social y modificar el pronóstico, pues no han sido afectados mayormente por la cronicidad de la enfermedad y presentan una sintomatología más leve que en etapas residuales. El presente trabajo pretende realizar una revisión de cómo los DCS están presentes desde etapas prodrómicas de la esquizofrenia y su importancia en la detección precoz de esta enfermedad.

Schizophrenia is a severe chronic disease that affects approximately 1 % of the world's population. Those who suffer this disease have serious deficits in social cognition (DSC), deficits that have been observed in first psychotic episode patients and first-degree relatives. The DSC determine the long-term prognosis in this disease and are susceptible to rehabilitation if they are detected early. Only recent studies have characterized deficits of social cognition in subjects with a high risk of developing chronic psychosis. These subjects present a unique opportunity to modify their social insertion and medical prognosis, as they have not been affected by the chronicity of the disease and present a milder symptomatology than in residual stages. This paper aims to make a review about how the DSC are present in schizophrenia from its prodromal stages and about its importance in the early detection of this disease.

Syzygium cumini (L.) Skeels improves metabolic and ovarian parameters in female obese rats with malfunctioning hypothalamus-pituitary-gonadal axis.

BACKGROUND: Obesity is a chronic and multifactorial disease characterized by increased adipose tissue. In females, obesity leads to reduced ovulation and lower chances of conception in diseases like polycystic ovary syndrome, making it important to characterize complementary medicine to attenuate such deleterious effects. Therefore, the aim of this study was to assess the effects of a hydroethanolic extract from Syzigium cumini leaves in female reproductive impairments present in the obesity model of neonatal L-monosodium glutamate injection. METHODS: Newborn Wistar rats received saline (CTRL) or L-monosodium glutamate 4 mg/g BW (MSG). At 90 days of age, CTRL and some MSG rats received saline, while others received hydroethanolic extract of S. cumini leaves (HESc 500 mg/kg/day, MSG-Syz group) for 30 consecutive days. Estrous cycle was determined by daily vaginal washes. On days 26 and 28 of treatment, oral glucose tolerance test and blood collection were performed for biochemical assessment. At the end, animals were euthanized during estrous phase; blood was collected to measure sex hormones and organs collected for weighing and histological evaluation. RESULTS: MSG-Syz showed reduced Lee Index, retroperitoneal fat pads and restored gluco-insulin axis. Moreover, HESc treatment reduced serum cholesterol levels when compared to MSG. Treatment with HESc did not restore the oligociclicity observed in obese animals, though MSG-Syz reestablished ovarian follicle health back to CTRL levels, with proliferating primordial follicles - these effects were followed by a decrease on periovarian adipocyte area. CONCLUSIONS: This is the first report to show the reversibility of the reproductive dysfunctions seen in MSG female rats through ethnopharmacological treatment. Moreover, it expands the use of HESc as a prominent tool to treat metabolic and reproductive disorders. Finally, we provide novel evidence that, without a functioning hypothalamus-pituitary-gonads axis, metabolic improvement is ineffective for estrous cyclicity, but critical for ovarian follicle health.

The effect of increased NaCl intake on rat brain endogenous µ-opioid receptor signalling.

Numerous studies demonstrate the significant role of central ß-endorphin and its receptor, the µ-opioid receptor (MOR), in sodium intake regulation. The present study aimed to investigate the possible relationship between chronic high-NaCl intake and brain endogenous MOR functioning. We examined whether short-term (4 days) obligatory salt intake (2% NaCl solution) in rats induces changes in MOR mRNA expression, G-protein activity and MOR binding capacity in brain regions involved in salt intake regulation. Plasma osmolality and electrolyte concentrations after sodium overload and the initial and final body weight of the animals were also examined. After 4 days of obligatory hypertonic sodium chloride intake, there was clearly no difference in MOR mRNA expression and G-protein activity in the median preoptic nucleus (MnPO). In the brainstem, MOR binding capacity also remained unaltered, although the maximal efficacy of MOR G-protein significantly increased. Finally, no significant alterations were observed in plasma osmolality and electrolyte concentrations. Interestingly, animals that received sodium gained significantly less weight than control animals. In conclusion, we found no significant alterations in the MnPO and brainstem in the number of available cell surface MORs or de novo syntheses of MOR after hypertonic sodium intake. The increased MOR G-protein activity following acute sodium overconsumption may participate in the maintenance of normal blood pressure levels and/or in enhancing sodium taste aversion and sodium overload-induced anorexia.

Resistance exercise enhances oxygen uptake without worsening cardiac function in patients with systolic heart failure: a systematic review and meta-analysis.

Recent literature suggests that resistance training (RT) improves peak oxygen uptake ([Formula: see text] peak), similarly to aerobic exercise (AE) in patients with heart failure (HF), but its effect on cardiac remodeling is controversial. Thus, we examined the effects of RT and AE on [Formula: see text] peak and cardiac remodeling in patients with heart failure (HF) via a systematic review and meta-analysis. MEDLINE, EMBASE, Cochrane Library and CINAHL, AMEDEO and PEDro databases search were extracted study characteristics, exercise type, and ventricular outcomes. The main outcomes were [Formula: see text] peak (ml kg-1 min-1), LVEF (%) and LVEDV (mL). Fifty-nine RCTs were included. RT produced a greater increase in [Formula: see text] peak (3.57 ml kg-1 min-1, P < 0.00001, I 2 = 0%) compared to AE (2.63 ml kg-1 min-1, P < 0.00001, I 2 = 58%) while combined RT and AE produced a 2.48 ml kg-1 min-1 increase in [Formula: see text]; I 2 = 69%) compared to control group. Comparison among the three forms of exercise revealed similar effects on [Formula: see text] peak (P = 0.84 and 1.00, respectively; I 2 = 0%). AE was associated with a greater gain in LVEF (3.15%; P < 0.00001, I 2 = 17%) compared to RT alone or combined exercise which produced similar gains compared to control groups. Subgroup analysis revealed that AE reduced LVEDV (- 10.21 ml; P = 0.007, I 2 = 0%), while RT and combined RT and AE had no effect on LVEDV compared with control participants. RT results in a greater gain in [Formula: see text] peak, and induces no deleterious effects on cardiac function in HF patients.

Association between inspiratory muscle weakness and slowed oxygen uptake kinetics in patients with chronic obstructive pulmonary disease.

Patients with chronic obstructive pulmonary disease (COPD) may have poor inspiratory muscle function, which reduces minute and alveolar ventilation, leading to increased hypoxemia and slow pulmonary oxygen uptake kinetics. However, little is known about the effect of inspiratory muscle weakness (IMW) on oxygen uptake kinetics in patients with COPD. Thus, we tested the hypothesis that COPD patients with IMW have slowed oxygen uptake kinetics. An observational study was conducted that included COPD patients with moderate to severe airflow limitation and a history of intolerance to exercise. Participants were divided into 2 groups: (IMW+; n = 22) (IMW-; n = 23) of muscle weakness. The maximal inspiratory, expiratory, and sustained inspiratory strength as well as the maximal endurance of the inspiratory muscles were lower in IMW+ patients (36 ± 9.5 cm H2O; 52 ± 14 cm H2O; 20 ± 6.5 cm H2O; 94 ± 84 s, respectively) than in IMW- patients (88 ± 12 cm H2O; 97 ± 28 cm H2O; 82.5 ± 54 cm H2O; 559 ± 92 s, respectively; p < 0.05). Moreover, the 6-min walk test and peak oxygen uptake were reduced in the IMW+ patients. During the constant work test, oxygen uptake kinetics were slowed in the IMW+ compared with IMW- patients (88 ± 29 vs 61 ± 18 s, p < 0.05). Our findings demonstrate that inspiratory muscle weakness in COPD is associated with slowed oxygen uptake kinetics, and thus, reduced functional capacity.

Novel antiplatelet role for a protein disulfide isomerase-targeted peptide: evidence of covalent binding to the C-terminal CGHC redox motif.

Essentials Inhibitors of protein disulfide isomerase (PDI) have been considered a new antithrombotic class. CxxC is a PDI-targeted peptide that has been previously shown to inhibit its reductase activity. CxxC binds to surface PDI and inhibits ADP- and thrombin-evoked platelet activation and aggregation. CxxC binds to Cys400 on CGHC redox motif of PDI a' domain, a site for PDI prothrombotic activity. SUMMARY: Background Protein disulfide isomerase (PDI) plays a major role in platelet aggregation, and its inhibitors have emerged as novel antithrombotic drugs. In previous work, we designed a peptide based on a PDI redox motif (CGHC) that inhibited both PDI reductase activity and PDI-modulated superoxide generation by neutrophil Nox2. Thus, we hypothesized that this peptide would also inhibit platelet aggregation by association with surface PDI. Methods Three peptides were used: CxxC, containing the PDI redox motif; Scr, presenting a scrambled sequence of the same residues and AxxA, with cysteines replaced by alanine. These peptides were tested under platelet aggregation and flow cytometry protocols to identify their possible antiplatelet activity. We labeled membrane free thiol and electrospray ionization liquid chromatography tandem mass spectrometry to test for an interaction. Results CxxC decreased platelet aggregation in a dose-dependent manner, being more potent at lower agonist concentrations, whereas neither AxxA nor Scr peptides exerted any effect. CxxC decreased aIIbb3 activation, but had no effect on the other markers. CxxC also decreased cell surface PDI pulldown without interfering with the total thiol protein content. Finally, we detected the addition of one CxxC molecule to reduced PDI through binding to Cys400 through mass spectrometry. Interestingly, CxxC did not react with oxidized PDI. Discussion CxxC has consistently shown its antiplatelet effects, both in PRP and washed platelets, corroborated by decreased aIIbb3 activation. The probable mechanism of action is through a mixed dissulphide bond with Cys400 of PDI, which has been shown to be essential for PDI's actions. Conclusion In summary, our data support antiplatelet activity for CxxC through binding to Cys400 in the PDI a0 domain, which can be further exploited as a model for sitedriven antithrombotic agent development.

Skeletal muscle metaboreflex in patients with chronic renal failure.

The sympathetic nervous system is affected in patients with chronic renal failure (CRF). This study tested the hypothesis that patients with CRF have an altered skeletal muscle metaboreflex. Twenty patients with CRF and 18 healthy subjects of similar age participated in the study. The muscle metaboreflex was determined based on heart rate (HR), mean arterial pressure, calf blood flow and calf vascular resistance (CVR) in response to handgrip exercise. The control of vascular resistance in the calf muscle mediated by the metaboreflex was estimated by subtracting the area under the curve with circulatory occlusion from that without occlusion. Arterial pressure and HR responses during exercise and recovery were similar in two groups of subjects. In the control group, CVR increased during exercise and remained elevated during circulatory occlusion, whereas no significant change was seen in the patients. Thus, the index of the metaboreflex was 7·82 ± 9·57 in the patients versus16·52 ± 14 units in the controls. The findings demonstrate that patients with CRF have a decreased vascular resistance response in the calf during the handgrip exercise, which suggests that CRF condition attenuates this reflex.

Spontaneous breathing trial in T-tube negatively impact on autonomic modulation of heart rate compared with pressure support in critically ill patients.

INTRODUCTION: Spontaneous breathing with a conventional T-piece (TT) connected to the tracheal tube orotraqueal has been frequently used in clinical setting to weaning of mechanical ventilation (MV), when compared with pressure support ventilation (PSV). However, the acute effects of spontaneous breathing with TT versus PSV on autonomic function assessed through heart rate variability (HRV) have not been fully elucidated. OBJECTIVE: The purpose of this study was to examine the acute effects of spontaneous breathing in TT vs PSV in critically ill patients. METHOD: Twenty-one patients who had received MV for ≥ 48 h and who met the study inclusion criteria for weaning were assessed. Eligible patients were randomized to TT and PSV. Cardiorespiratory responses (respiratory rate -ƒ, tidal volume-VT , mean blood pressure (MBP) and diastolic blood pressure (DBP), end tidal dioxide carbone (PET CO2 ), peripheral oxygen saturation (SpO2 ) and HRV indices in frequency domain (low-LF, high frequency (HF) and LF/HF ratio were evaluated. RESULTS: TT increased ƒ (20 ± 5 vs 25 ± 4 breaths/min, P<0.05), MBP (90 ± 14 vs 94 ± 18 mmHg, P<0.05), HR (90 ± 17 vs 96 ± 12 beats/min, P<0.05), PET CO2 (33 ± 8 vs 48 ± 10 mmHg, P<0.05) and reduced SpO2 (98 ± 1.6 vs 96 ± 1.6%, P<0.05). In addition, LF increased (47 ± 18 vs 38 ± 12 nu, P<0.05) and HF reduced (29 ± 13 vs 32 ± 16 nu, P<0.05), resulting in higher LF/HF ratio (1.62 ± 2 vs 1.18 ± 1, P<0.05) during TT. Conversely, VT increased with PSV (0.58 ± 0.16 vs 0.50 ± 0.15 L, P<0.05) compared with TT. CONCLUSION: Acute effects of TT mode may be closely linked to cardiorespiratory mismatches and cardiac autonomic imbalance in critically ill patients.