Diaphragm thickness and mobility elicited by two different modalities of inspiratory muscle loading in heart failure participants: A randomized crossover study.

OBJECTIVES: To analyze diaphragmatic thickness, at end-inspiration and end-expiration, diaphragmatic thickening index and mobility via US under two different modalities of inspiratory muscle loading, in two different modalities of inspiratory muscle loading and different load intensities at full-vital capacity maneuvers and the relationship between diaphragmatic thickness with pulmonary function tests in participants with HF. METHODS: This randomized crossover trial, enrolled with 17 HF subjects, evaluated diaphragm thickness (Tdi, mm), fractional thickness (TFdi, %), and mobility (mm) US during low and high intensities (30% and 60% of maximal inspiratory pressure-MIP) with two modalities of inspiratory muscle loading mechanical threshold loading (MTL) and tapered flow-resistive loading (TFRL). RESULTS: Both MTL and TFRL produced a increase in Tdi, but only with high intensity loading compared to baseline-2.21 (0.26) vs. 2.68 (0.33) and 2.73 (0.44) mm; p = .01. TFdi was greater than baseline under all conditions, except during low intensity of TFRL. Diaphragm mobility was greater than baseline under all conditions, and high intensity of TFRL elicited greater mobility compared to all other conditions. Additionally, baseline Tdi was moderately correlated with pulmonary function tests. CONCLUSIONS: MTL and TFRL modalities elicit similar increases in diaphragm thickness at loads, but only during high intensity loading it was greater than baseline. Diaphragm mobility was significantly greater than baseline under both loads and devices, and at high intensity compared to low intensity, although TFRL produced greater mobility compared to modalities of inspiratory muscle loading. There is an association between diaphragm thickness and pulmonary function tests.

Efficacy of home-based inspiratory muscle training in patients post-covid-19: Protocol for a randomized clinical trial.

INTRODUCTION: Current evidence suggests the emergence of a novel syndrome (long COVID syndrome) due to sequels and persistent COVID-19 symptoms. Respiratory muscle training improves respiratory muscle strength, exercise capacity, diaphragm thickness, and dyspnea, especially in patients with decreased respiratory muscle strength. This study aims to evaluate the effectiveness of a protocol for home-based inspiratory muscle training to improve respiratory muscle strength, dyspnea, and quality of life of patients post-COVID-19. METHODS AND ANALYSES: This randomized, controlled, double-blind clinical trial will be conducted at the Instituto de Medicina Tropical of Universidade Federal do Rio Grande do Norte (Brazil). Sample size will be determined using maximal inspiratory pressure after a pilot study with five patients per group (total of 10 patients). Patients included in the study will be evaluated in three moments: pre-training (initial), post-training (three weeks), and retention (24 weeks). The sample will be randomized in two groups: active (IMT using 30% of IMT and load increase of 10% of initial IMT every week. Patients will perform 30 repetitions, twice a day (morning and afternoon), for seven consecutive days, and six weeks) and SHAM (IMT without load). The following measurements will be assessed: anthropometry, respiratory muscle strength, pulmonary volume and capacity, dyspnea, perception of effort and lower limb fatigue, handgrip strength, functional capacity, anxiety, depression, and functional status. After initial evaluation, all patients will receive a POWERbreathe® (POWERbreathe®, HaB Ltd, Southam, UK) device to perform the training. Normality will be verified using Shapiro-Wilk or Kolmogorov-Smirnov, according to the number of patients included. Variables presenting nonparametric distribution will be compared using Wilcoxon (intragroup analysis) and Mann-Whitney test (intergroup analysis), whereas repeated measures two-way ANOVA will be performed in case of parametric distribution. Dunn's post hoc test will be used to identify significant differences in the two-way ANOVA test. PRIMARY OUTCOMES: Respiratory muscle strength, dyspnea, and quality of life of post-COVID-19 patients. SECOND OUTCOMES: Pulmonary function, dyspnea, exercise tolerance, handgrip strength, anxiety, depression, and functional status. TRIAL REGISTRATION: Trial register number NCT05077241.

Failure of Noninvasive Ventilation in Acute Respiratory Failure is Associated with Higher Mortality in Patients with Solid Tumors: A Retrospective Cohort Study.

BACKGROUND: Noninvasive Ventilation (NIV) is a well-established treatment for Acute Respiratory Failure (ARF) in hematological cancer. However, the NIV impact on mortality in patients with solid tumors is unclear. OBJECTIVE: To define the factors associated with NIV failure and mortality and to describe the mortality risk of patients with solid tumors requiring NIV for ARF treatment in the intensive care unit (ICU). METHODS: A retrospective cohort study of patients with solid tumors admitted into an ICU between Jan 2016 and Dec 2017, for cancer treatment, with ARF diagnosis that had used the NIV as first-line treatment. Our primary outcome was ICU and in-hospital mortality. The secondary outcome was NIV failure. A Cox proportional hazards regression was used to identify variables associated with mortality and NIV failure. Kaplan-Meier analyses were performed to demonstrate cumulative survival. RESULTS: A total of 226 patients with solid tumors were included. The ICU and hospital mortality rates were 57.5% and 69.5%, respectively. NIV failed in 52.2% of the patients. The use of vasopressors (HR 2.48 [95% CI: 1.43-4.30] p = 0.001), baseline lactate (HR 1.20 [95% CI: 1.07-1.35] p = 0.003), baseline PaO2/FiO2 ratio (HR1.33 [1.11-1.55] p = 0.002), and NIV success (HR0.17 [95% CI: 0.10-0.27] p = 0.005) was independently associated with hospital mortality. The use of vasopressors (HR 2.58 [95% CI: 1.41-4.73] p = 0.02), NIV duration (HR 0.93 [95% CI: 0.89-0.97] p = 0.003), and baseline lactate (HR 1.13 [95% CI: 1.06-1.20] p = 0.001) was associated with NIV failure. CONCLUSIONS: NIV failure was independently associated with an increase in both ICU and hospital mortality rates. In patients with NIV therapy indication, the duration of this intervention was associated with NIV failure.

Inspiratory muscle strength and six-minute walking distance in heart failure: Prognostic utility in a 10 years follow up cohort study.

BACKGROUND: Maximal inspiratory pressure (PImax) and 6-minutes walk distance test (6MWD) may be more available and feasible alternatives for prognostic assessment than cardiopulmonary testing. We hypothesized that the PImax and 6MWD combination could improve their individual accuracy as risk predictors. We aimed to evaluate PImax ability as a mortality predictor in HF and whether the combination to 6MWD could improve risk stratification. METHODS: Prospective cohort from HF Clinics of three University Hospitals. PImax, 6MWD and pVO2 were obtained at baseline. The end point was all cause mortality. RESULTS: Consecutive 256 individuals (50% woman, 57.4±10.4years) with low ejection fraction (LVEF) (31.8±8.6%) were followed up to 10years. During a median follow-up of 34.7 (IQR 37) months, 110 participants died. Mean±SD values were: pVO2 14.9±5.1mL/kg/min, PImax 5.5±1.3kPa and 6MWD 372±118m. In multivariate Cox regression, pVO2, PImax, 6MWD and LVEF were independent mortality predictors. The pVO2 showed gold standard accuracy, followed by PImax (AUC = 0.84) and 6MWD (AUC = 0.74). Kaplan-Meier mean survival time (MST±SE) for lower (≤5.0kPa) and higher (>6.0kPa) PImax tertiles, were 37.9±2.8months and 105.0±5.2months respectively, and addition of 6MWD did not restratified risk. For intermediate PImax tertile, MST was 81.5±5.5months, but adding 6MWD, MST was lower (53.3±7.6months) if distance was ≤350m and higher (103.1±5.7months) for longer distances. CONCLUSION: PImax is an independent mortality predictor in HF, more accurate than 6MWD and LVEF. Addition of 6MWD empowers risk stratification only for intermediate PImax tertile. Although less accurate than pVO2, this simpler approach could be a feasible alternative as a prognostic assessment.

Faster oxygen uptake, heart rate, and ventilatory kinetics in stepping compared with cycle ergometry in patients with COPD during moderate-intensity exercise.

Step tests are a stressful and feasible cost-effective modality to evaluate aerobic performance. However, the eccentric in addition to concentric muscle contractions of the legs on stepping emerge as a potential speeding factor for cardioventilatory and metabolic adjustments towards a steady-state, since eccentric contractions would prompt an earlier and stronger mechanoreceptor activation, as well as higher heart rate/cardiac output adjustments to the same metabolic demand. Moreover, shorter tests are ideal for exercise-limited subjects. Nine subjects with chronic obstructive pulmonary disease were invited to participate in comprehensive lung function tests and constant work tests performed on different days at a 90% gas exchange threshold for 6 min, in single-step tests or cycle ergometry. After careful monoexponential regression modelling, statistically relevant faster phase II time constants for oxygen uptake (45 ± 18 s vs 53 ± 17 s, p = 0.017) and minute ventilation (61 ± 13 s vs 74 ± 17 s, p = 0.027) were observed in the 6-min step tests compared with cycle ergometry, respectively. Despite an absence of heart rate time constant difference (43 ± 20 s vs 69 ± 46 s, p = 0.167), there was a significantly faster rate constant toward a steady state for heart rate (p = 0.02). In addition, 4-min compared with 6-min analysis presented similar results (p > 0.05), providing an appropriate steady-state. We conclude that step tests might elicit faster time constants compared with cycle ergometry, at the same average metabolic level, and 4-min analysis has similar mean errors compared with 6-min analysis within an acceptable range. New studies, comprising mechanisms and detailed physiological backgrounds, are necessary.

CPAP and EPAP elicit similar lung deflation in a non-equivalent mode in GOLD 3-4 COPD patients.

INTRODUCTION: Lung hyperinflation is associated with inspiratory muscle strength reduction, nocturnal desaturation, dyspnea, altered cardiac function and poor exercise capacity in advanced COPD. OBJECTIVES: We investigated the responses of inspiratory capacity (IC) and inspiratory muscle strength (PImax), comparing continuous positive airway pressure (CPAP) and expiratory positive airway pressure (EPAP) with the main hypothesis that there would be similar effects on lung deflation. METHODS: Eligible patients were submitted to 10 cmH2 O CPAP and EPAP on different days, under careful ECG (HR) and peripheral oxygen saturation (SpO2 ) monitoring. RESULTS: Twenty-one eligible COPD patients were studied (13 male/8 female, FEV1 % predicted of 36.5 ± 9.8). Both CPAP and EPAP demonstrated significant post-pre (Δ) changes for IC and PImax, with mean ΔIC for CPAP and EPAP of 200 ± 100 mL and 170 ± 105 mL (P = .001 for both) in 13 and 12 patients (responders) respectively. There were similar changes in % predicted IC and PImax (∼7%, P = .001 for both) for responders and poor responder/non-responder agreement depending on CPAP/EPAP mode (Kappa = .113, P = .604). There were no differences in CPAP and EPAP regarding intensity of lung deflation (P =.254) and no difference was measured regarding HR (P = .235) or SpO2 (P = .111). CONCLUSIONS: Both CPAP and EPAP presented a similar effect on lung deflation, without guaranteeing that the response to one modality would be predictive of the response to the other.

Effects of transcutaneous electrical nerve stimulation (TENS) on arterial stiffness and blood pressure in resistant hypertensive individuals: study protocol for a randomized controlled trial.

BACKGROUND: Resistant hypertension (RH) treatment requires an adequate and intense therapeutic approach. However, the results are not always satisfactory despite intensive treatment. Of the different pathophysiological mechanisms involved in the pathogenesis of RH, sympathetic overstimulation and therapies that block the sympathetic system have been widely studied. These approaches, however, are invasive and expensive. Another possible approach is by transcutaneous electrical nerve stimulation (TENS), a noninvasive method that modulates activity by using low-frequency transcutaneous electrical stimulation to inhibit primary afferent pathways. Thus, the current study will evaluate the effect of applying TENS in the cervicothoracic region of subjects with RH and will seek to develop a new low-cost and readily available therapy to treat this group of hypertensive individuals. METHODS/DESIGN: This is a randomized, single blind (subject), parallel-assignment study controlled with a sham group and including participants aged 40 to 70 years with resistant hypertension. The trial has two arms: the treatment and control (sham group). The treatment group will be submitted to the stimulation procedure (TENS). The sham group will not be submitted to stimulation. The primary outcomes will be a reduction in the peripheral blood pressure and adverse events. The secondary outcomes will be a reduction the central blood pressure. The study will last 30 days. The sample size was calculated assuming an alpha error of 5 % to reject the null hypothesis with a statistical power of 80 %, thereby resulting in 28 participants per group (intervention versus sham). DISCUSSION: In recent decades, RH has become very common and costly. Adequate control requires several drugs, and in many cases, treatment is not successful. Sympathetic nervous system inhibition by renal denervation and central inhibition have significant effects in reducing BP; however, these treatments are costly and invasive. Another type of sympathetic nervous system inhibition can also be noninvasively achieved by electric current. Therefore, the application of TENS may be a new therapeutic option for treating resistant hypertensive individuals. TRIAL REGISTRATION: Clinical Trials NCT02365974.

Evaluation of the best environment for the six-minute walk test / Avaliação do melhor ambiente para o teste de caminhada de seis minutos

AbstractIntroduction The purpose of the six-minute walk test (6MWT) is to evaluate cardiopulmonary capacity using a low-cost test that is easy to administer, generally well tolerated by different populations and reflects one’s performance on activities of daily living. However, few studies have been conducted to determine the difference between performing the 6MWT indoors and outdoors.Objective The aim of the present study was to compare the distance covered on the 6MWT performed indoors and outdoors and evaluate the following physiological variables: heart rate, blood pressure and the subjective sensation of shortness of breath, using the Borg perceived exertion scale.Materials and methods A prospective, randomized, clinical trial was conducted involving eight healthy females not engaged in regular physical activity, with mean age 23.75 ± 1.67 years. Each subject performed the 6MWT indoors and outdoors with a 30-minute interval between tests. The order of the tests was determined randomly.Results The mean distance traveled was 578 ± 50.07 m on the outdoor trial and 579.95 ± 45.35 m on the indoor trial (p = 0.932). The mean physiological variables were 82.25 ± 11.02 bpm (indoors) versus 84.38 ± 9.42 bpm (outdoors) for heart rate, 121.88 ± 10.28 mmHg (indoors)versus 118.75 ± 19.40 mmHg (outdoors) for systolic blood pressure, 81.88 ± 9.74 mmHg (indoors) versus 80.50 ± 7.89 mmHg (outdoors) for diastolic blood pressure and a mean score of 12 on the perceived exertion score in both environments.Conclusions The present data demonstrate no differences in the distance walked on the 6MWT or the physiologic variables of participants between the indoor and outdoor trials.

ResumoIntrodução O objetivo do teste de caminhada de seis minutos (TC6) é avaliar a capacidade cardiorrespiratória por meio de um teste de baixo custo e de fácil administração, sendo bem tolerado por diferentes populações, e que reflita a realização das atividades da vida diária. Entretanto, poucos estudos têm sido realizados para determinar a diferença entre a realização do TC6 em ambientes fechados e ao ar livre.Objetivo O presente estudo teve como objetivo comparar a distância percorrida no TC6 realizado em ambientes fechado e ao ar livre e avaliar as seguintes variáveis fisiológicas: frequência cardíaca, pressão arterial e a sensação subjetiva de falta de ar, utilizando a escala de percepção de esforço de Borg.Materiais e métodos Um ensaio clínico randomizado prospectivo foi conduzido envolvendo oito mulheres saudáveis não praticantes de atividade física regular, com média de idade de 23,75 ± 1,67 anos. As participantes realizaram o TC6 nos dois ambientes com um intervalo de 30 minutos entre os testes. A ordem dos testes foi determinada aleatoriamente.Resultados A distância média percorrida foi de 578 ± 50,07 m ao ar livre e 579,95 ± 45,35 m no ambiente fechado (p = 0,932). As variáveis fisiológicas médias foram 82,25 ± 11,02 bpm (fechado) versus 84,38 ± 9,42 bpm (ar livre) para a frequência cardíaca, 121,88 ± 10,28 mmHg (fechado) versus 118,75 ± 19,40 mmHg (ar livre) para a pressão arterial sistólica, 81,88 ± 9,74 mmHg (fechado) versus 80,50 ± 7,89 mmHg (ar livre) para a pressão arterial diastólica e uma pontuação média de 12 pontos na escala de esforço percebido em ambos os ambientes.Conclusão Os dados demonstraram que não há diferenças nas distâncias percorridas ou entre as variáveis fisiológicas dos participantes durante o TC6 nos ambientes fechado e ao ar livre.

Oxidative damage induced by cigarette smoke exposure in mice: impact on lung tissue and diaphragm muscle.

OBJECTIVE: To evaluate oxidative damage (lipid oxidation, protein oxidation, thiobarbituric acid-reactive substances [TBARS], and carbonylation) and inflammation (expression of phosphorylated AMP-activated protein kinase and mammalian target of rapamycin [p-AMPK and p-mTOR, respectively]) in the lung parenchyma and diaphragm muscles of male C57BL-6 mice exposed to cigarette smoke (CS) for 7, 15, 30, 45, or 60 days. METHODS: Thirty-six male C57BL-6 mice were divided into six groups (n = 6/group): a control group; and five groups exposed to CS for 7, 15, 30, 45, and 60 days, respectively. RESULTS: Compared with control mice, CS-exposed mice presented lower body weights at 30 days. In CS-exposed mice (compared with control mice), the greatest differences (increases) in TBARS levels were observed on day 7 in diaphragm-muscle, compared with day 45 in lung tissue; the greatest differences (increases) in carbonyl levels were observed on day 7 in both tissue types; and sulfhydryl levels were lower, in both tissue types, at all time points. In lung tissue and diaphragm muscle, p-AMPK expression exhibited behavior similar to that of TBARS. Expression of p-mTOR was higher than the control value on days 7 and 15 in lung tissue, as it was on day 45 in diaphragm muscle. CONCLUSION: Our data demonstrate that CS exposure produces oxidative damage, not only in lung tissue but also (primarily) in muscle tissue, having an additional effect on respiratory muscle, as is frequently observed in smokers with COPD.

Oxidative damage induced by cigarette smoke exposure in mice: impact on lung tissue and diaphragm muscle, / Dano oxidativo induzido por exposição a fumaça de cigarro em camundongos: impacto sobre o pulmão e o músculo diafragma

OBJECTIVE: To evaluate oxidative damage (lipid oxidation, protein oxidation, thiobarbituric acid-reactive substances [TBARS], and carbonylation) and inflammation (expression of phosphorylated AMP-activated protein kinase and mammalian target of rapamycin [p-AMPK and p-mTOR, respectively]) in the lung parenchyma and diaphragm muscles of male C57BL-6 mice exposed to cigarette smoke (CS) for 7, 15, 30, 45, or 60 days. METHODS: Thirty-six male C57BL-6 mice were divided into six groups (n = 6/group): a control group; and five groups exposed to CS for 7, 15, 30, 45, and 60 days, respectively. RESULTS: Compared with control mice, CS-exposed mice presented lower body weights at 30 days. In CS-exposed mice (compared with control mice), the greatest differences (increases) in TBARS levels were observed on day 7 in diaphragm-muscle, compared with day 45 in lung tissue; the greatest differences (increases) in carbonyl levels were observed on day 7 in both tissue types; and sulfhydryl levels were lower, in both tissue types, at all time points. In lung tissue and diaphragm muscle, p-AMPK expression exhibited behavior similar to that of TBARS. Expression of p-mTOR was higher than the control value on days 7 and 15 in lung tissue, as it was on day 45 in diaphragm muscle. CONCLUSION: Our data demonstrate that CS exposure produces oxidative damage, not only in lung tissue but also (primarily) in muscle tissue, having an additional effect on respiratory muscle, as is frequently observed in smokers with COPD. .

OBJETIVO: Avaliar o dano oxidativo (oxidação lipídica, oxidação proteica, thiobarbituric acid-reactive substances [TBARS, substâncias reativas ao ácido tiobarbitúrico], e carbonilação) e inflamação (expressão de phosphorylated AMP-activated protein kinase e de phosphorylated mammalian target of rapamycin (p-AMPK e p-mTOR, respectivamente) em tecido pulmonar e músculos do diafragma em camundongos C57BL/6 machos expostos à fumaça de cigarro (FC) por 7, 15, 30, 45 ou 60 dias. MÉTODOS: Trinta e seis camundongos machos da espécie C57BL/6 foram divididos em seis grupos (n = 6/grupo): grupo controle e 5 grupos expostos a FC por 7, 15, 30, 45 e 60 dias, respectivamente. RESULTADOS: Comparados aos camundongos controle, os camundongos expostos à FC apresentaram menor peso corporal em 30 dias. Nos camundongos expostos à FC (comparados aos controle) as maiores diferenças (aumentos) nos níveis de TBARS foram observados no dia 7 no músculo diafragma, comparado ao dia 45 em tecido pulmonar; as maiores diferenças (aumentos) nos níveis de carbonilas foram observados no dia 7 em ambos os tipos de tecido; e os níveis de sulfidrilas foram menores, nos dois tipos de tecidos, em todos os tempos. No tecido pulmonar e no músculo diafragma, a expressão de p-AMPK exibiu um comportamento semelhante ao dos níveis de TBARS. A expressão de p-mTOR foi maior que o valor controle nos dias 7 e 15 no tecido pulmonar, assim como no dia 45 no músculo diafragma. CONCLUSÕES: Nossos dados demonstram que a exposição à FC produz dano oxidativo tanto no tecido pulmonar quanto (primariamente) no tecido muscular, tendo um efeito adicional no músculo respiratório, como é frequentemente observado em fumantes com DPOC. .

Fluxo sangüíneo muscular na insuficiência cardíaca: interação entre fatores centrais e locais / Muscle blood flow in heart failure: interaction between central and local factors

A intolerância ao exercício é uma característica marcante da insuficiência cardíaca. Diversos mecanismos, como anormalidades no metabolismo muscular, no consumo de oxigênio do músculo e principalmente no fluxo sangüíneo muscular, têm sido documentados em pacientes com insuficiência cardíaca. Contudo, a relação entre a tolerância ao exercício e perfusão muscular no exercício é ainda controversa neste estado. Diversos mecanismos têm sido propostos na participação da regulação da hiperemia relacionada ao exercício, incluindo os mecanismos neural, endotelial e a bomba muscular. O propósito desta revisão é apresentar as evidências experimentais e clínicas com relação ao controle da perfusão muscular no exercício na insuficiência cardíaca. Existe um consenso geral de que a insuficiência cardíaca crônica esteja associada à vasoconstrição periférica e à marcante elevação da atividade do sistema nervoso autônomo simpático. Evidências recentes sugerem, ainda, que a modulação inadequada da atividade vasoconstritora simpática, a disfunção endotelial e os mecanismos anormais de controle da bomba muscular podem ser responsáveis pela resposta vasodilatadora inadequada ao exercício nesses pacientes. Contudo, a interação entre os mecanismos de controle do fluxo sangüíneo muscular no exercício e, sobretudo, como esses mecanismos afetam a tolerância ao exercício na insuficiência cardíaca ainda precisam ser melhor investigados

Exercise intolerance is a hallmark of heart failure. Several mechanisms, such as abnormalities in muscle metabolism, muscle oxygen uptake and especially muscle blood flow have been documented in patients with heart failure. However, the relation between exercise tolerance and muscle perfusion during exercise is still controversial in this state. Several mechanisms have been proposed to be involved in the regulation of exercise hyperemia, including neural, endothelial and muscle pump mechanisms. The purpose of this review is to present experimental and clinical evidence regarding muscle perfusion control during exercise in heart failure. There is a general consensus that chronic heart failure is associated with peripheral vasoconstriction and marked elevation in sympathetic nervous system activity. Recent evidence also suggests that impaired modulation of sympathetic vasoconstriction, endothelial dysfunction and abnormal muscle pump mechanisms may be responsible for the blunted vasodilator responses to exercise in these patients. However, the interactions between muscle blood flow control mechanisms during exercise and especially how these factors affect exercise tolerance still need to be investigated in heart failure