Effects of intradialytic inspiratory muscle training at different intensities on diaphragm thickness and functional capacity: clinical trial protocol in patients undergoing haemodialysis.

INTRODUCTION: Patients with end-stage renal disease (ESRD) undergoing haemodialysis (HD) commonly present with a sedentary behaviour and reduced functional capacity, factors that can compromise their prognosis. Intradialytic inspiratory muscle training (IMT) can increase respiratory muscle strength and, consequently, improve functional capacity, besides being easy to apply, cheap and performed in a supervised setting. However, few studies show the effects of this type of training applied at different intensities in this population. This study aims to compare the effects of IMT at different intensities in adults with ESRD undergoing HD. METHODS AND ANALYSIS: A randomised, double-blind, sham-controlled trial will be conducted on 36 subjects randomly allocated into three groups: IMT at intensities of 30% or 50% of maximal inspiratory pressure (intervention groups), or 10% of maximal inspiratory pressure (sham-IMT). All the interventions will be supervised and performed three times per week, for 12 weeks, totalling 36 sessions. The primary outcomes are the 6-minute walk test, diaphragm thickness and the response of VO2peak post-intervention. Respiratory muscle strength, 24-hour ambulatory blood pressure measurement and the Kidney Disease Quality of Life 36-item short form survey will be evaluated as secondary outcomes. ETHICS AND DISSEMINATION: This study has been approved by the Research Ethics Committee of the Hospital de Clínicas de Porto Alegre (ID: 2020-0458). The results of this study will be disseminated by conference presentations and peer-reviewed journal. TRIAL REGISTRATION NUMBER: NCT04660383.

Ventilatory Muscle Training for Early Cardiac Rehabilitation Improved Functional Capacity and Modulated Vascular Function of Individuals Undergoing Coronary Artery Bypass Grafting: Pilot Randomized Clinical Trial.

Background: Cardiac rehabilitation with aerobic exercises is the first strategy for nonpharmacological treatment in the postoperative period of individuals undergoing coronary artery bypass grafting (CABG) to improve functional capacity and vascular health. However, other exercise modalities remain uncertain regarding the same benefits. Objectives: Evaluation of the effect of different modalities of exercise, such as early cardiac rehabilitation on subjects submitted to CABG in the six-minute walk test (6-MWT) and on the percentage of flow-mediated dilatation (FMD) of the brachial artery. Methods: A randomized clinical trial in which 15 patients (62.7 ± 6.7 years) who underwent CABG were randomly assigned to the following groups: isometric (IG, Handgrip Jamar®), ventilatory muscle training (VG, PowerBreathe®) and control (CG, conventional respiratory and motor physiotherapy). All patients were attended to physically twice a day (20 min/session) for a consecutive week after the CABG (hospital admission). Functional capacity was assessed by 6-MWT and endothelial function was assessed through the technique of FMD, before and after (~7 days) admission to CABG. The doppler ultrasound videos were analyzed by Cardiovascular Suite® software (Quipu, Pisa, Italy) to measure %FMD. Statistics: Generalized estimation equation, followed by Bonferroni post hoc (p < 0.05). Results: Systolic, diastolic and mean arterial pressure (SBP/DBP/MAP, respectively) were 133, 76 and 95 mmHg. The groups presented walking meters (m) distance before and after intervention of: IGbasal 357.80 ± 47.15 m vs. IGpost 306.20 ± 61.63 m, p = 0.401 (+51 m); VGbasal 261.50 ± 19.91 m vs. VGpost 300.75 ± 26.29 m, p = 0.052 (+39 m); CG basal 487.83 ± 83.23 m vs. CGpost 318.00 ± 31.08, p = 0.006 (−169 m). %FMD before and after intervention was IGbasal 10.4 ± 4.8% vs. IGpost 2.8 ± 2.5%, p = 0.152; VGbasal 9.8 ± 5.1% vs. VGpost 11.0 ± 6.1%, p = 0.825; CGbasal 9.2 ± 15.8% vs. CGpost 2.7 ± 2.6%, p = 0.710 and resting mean basal blood flow was IGbasal 162.0 ± 55.0 mL/min vs. IGpost 129.9 ± 63.7 mL/min, p = 0.662; VGbasal 83.74 ± 12.4 mL/min vs. VGpost 58.7 ± 17.1 mL/min, p = 0.041; CGbasal 375.6 ± 183.7 mL/min vs. CGpost 192.8 ± 115.0 mL/min, p = 0.459. Conclusions: Ventilatory muscle training for early cardiac rehabilitation improved acute functional capacity and modulated mean flow of individuals undergoing CABG.

Short period of high-intensity inspiratory muscle training improves inspiratory muscle strength in patients with chronic kidney disease on hemodialysis: a randomized controlled trial.

BACKGROUND: Chronic kidney disease is a complex disease that impacts multiple organs and systems (including musculoskeletal and cardiorespiratory) leading to reduction of functional capacity. OBJECTIVE: The aim of this study was to investigate the effect of a short period of high intensity inspiratory muscle training on maximum inspiratory pressure, functional capacity and endothelial function of chronic kidney disease patients on hemodialysis. METHODS: This randomized controlled trial enrolled 25 patients who were allocated into two groups: intervention (IMTG=14) and control (CG=11) groups. Intervention patients received the exercise protocol over a period of 5 weeks, 6 times per week, with each session consisting of 5 sets of 10 repetitions with an initial load of 50% progressing to 70% of maximum inspiratory pressure , measured weekly. The primary outcome was inspiratory muscle strength and the secondary outcomes were functional capacity and endothelial function evaluated before and after the training protocol. RESULTS: The inspiratory muscle training induced a marked improvement in maximum inspiratory pressure which was evident after the training period (mean difference 19.0cmH2O - 95%CI 0.4-37.5; IMTG: 102±25.7cmH2O vs CG: 83±19.2; p=0.046). The magnitude of maximum inspiratory pressure improvement was 33.5% at the end of the protocol for the IMTG. Functional capacity and endothelial function did not vary between or within groups. CONCLUSION: A short period of high-intensity inspiratory muscle training for five weeks was able to improve inspiratory muscle strength of chronic kidney disease patients on hemodialysis (ClinicalTrials.gov registration NCT03082404).

Treating periodontal disease in patients with myocardial infarction: A randomized clinical trial.

BACKGROUND: Periodontitis has been associated with coronary artery disease, but the impact of a periodontal treatment on the endothelial function of patients with a recent ST-segment elevation myocardial infarction (STEMI) was not investigated. METHODS: Randomized controlled trial (NCT02543502). Patients admitted between August 2012 and January 2015 were included. Patients were screened during the index hospitalization for STEMI, and those with severe periodontal disease were randomized 2 weeks later to periodontal treatment or to control. The primary endpoint of this trial was the between group difference in the variation of flow-mediated vasodilation (FMD) in the brachial artery assessed by ultrasound from baseline to the 6-month follow-up. Secondary outcomes were cardiovascular events, adverse effects of periodontal treatment and inflammatory markers. RESULTS: Baseline characteristics were balanced between patients in the intervention (n = 24) and control groups (n = 24). There was a significant FMD improvement in the intervention group (3.05%; p = .01), but not in the control group (-0.29%; p = .79) (p = .03 for the intergroup comparison). Periodontal treatment was not associated with any adverse events and the inflammatory profile and cardiovascular events were not significantly different between both groups. CONCLUSIONS: Treatment of periodontal disease improves the endothelial function of patients with a recent myocardial infarction, without adverse clinical events. Larger trials are needed to assess the benefit of periodontal treatment on clinical outcomes. CLINICAL TRIAL REGISTRATION: NCT02543502 (https://clinicaltrials.gov/ct2/show/NCT02543502?term=NCT02543502&rank=1).

Intradialytic training in patients with end-stage renal disease: a systematic review and meta-analysis of randomized clinical trials assessing the effects of five different training interventions.

OBJECTIVE: Patients with end-stage renal disease (ESRD) undergoing hemodialysis may have reduced dialysis adequacy (Kt/V), low cardiorespiratory fitness, and worse prognosis. Different types of intradialytic training (IDT) may serve as an adjunct therapy for the management of the ESRD. This systematic review and meta-analysis aimed to assess the impact of different types of IDT on clinical outcomes and functional parameters in ESRD. METHODS: PubMed, Embase, CINAHL, Cochrane CENTRAL, Scopus, SPORTDiscus, and Google Scholar were searched for randomized clinical trials in adult patients with ESRD which compared IDT with usual care (UC), without language restrictions and published up to July 2019; a handsearch of references was also performed. Certainty of evidence was assessed using GRADE, and risk of bias in primary studies with the RoB 1.0 tool. RESULTS: Fifty studies were included (n = 1757). Compared to UC, aerobic IDT improved Kt/V (WMD = 0.08), VO2peak (WMD = 2.07 mL/kg/min), 6-minute walk test (6MWT) distance (64.98 m), reduced systolic blood pressure (- 10.07 mmHg) and C-reactive protein (- 3.28 mg/L). Resistance training increased 6MWT distance (68.50 m). Combined training increased VO2peak (5.41 mL/kg/min) and reduced diastolic blood pressure (- 5.76 mmHg). Functional electrostimulation (FES) and inspiratory muscle training (IMT) improved 6MWT distance (54.14 m and 117.62 m, respectively). There was no impact on total cholesterol, interleukin-6, or hemoglobin levels. There was no difference in incidence of adverse events between the IDT and control groups. The certainty of evidence was variable according to the GRADE scale, with most outcomes rated very low certainty. The risk of bias assessment of primary studies showed unclear risk in most. CONCLUSIONS: Aerobic, resistance, and combined training during hemodialysis, as well as FES and IMT, demonstrated to be effective for the treatment of the patient with ESRD. Our data should be interpreted in light of the unclear risk of bias of most evaluated articles and the low to very low certainty of evidence for evaluated outcomes. PROSPERO REGISTRATION ID: CRD42017081338. DATA SHARING REPOSITORY: https://osf.io/fpj54/.

Quality of life as a predictor of hospitalization in patients with chronic kidney disease on hemodialysis: a retrospective cohort study

Introduction: As medical advances are achieved in the care of chronically ill patients, there is increasing evidence that health-related quality of life (QoL) is associated with poor outcomes, including hospitalization and death. This study aimed to evaluate QoL as a predictor of hospitalization and death in patients with chronic kidney disease (CKD) on hemodialysis. Methods: A retrospective cohort study of 108 patients with CKD on hemodialysis with 24-month follow-up. QoL was assessed by the Kidney Disease Quality of Life Short-Form (KDQOL-SF), including time to first hospitalization and death as outcomes. Results: The highest KDQOL-SF scores at baseline were observed in Sexual function, Dialysis staff encouragement, and Cognitive function, while the lowest scores were observed in Working status, Role physical, and Energy/fatigue. There was an association of Overall health and Role emotional domains with shorter time to first hospitalization. Data analyzed were insufficient to indicate an association of QoL with mortality in this population. Conclusion: QoL was associated with time to first hospitalization in patients with CKD on hemodialysis, but the results were not sufficient to indicate its association with mortality. (AU)

Intradialytic neuromuscular electrical stimulation reduces DNA damage in chronic kidney failure patients: a randomized controlled trial.

BACKGROUND: Chronic kidney failure (CKF) patients on renal replacement therapies exhibit elevated levels of DNA lesions and this is directly related to high mortality. OBJECTIVE: This study aimed to evaluate the effect of neuromuscular electrical stimulation (NMES) on genomic damage in CKF patients on conventional haemodialysis (HD). METHODS: Twenty-one patients with CKF on HD were randomized into control (CG =10) or neuromuscular electrical stimulation (NMESG = 11) groups. NMES was applied on the quadriceps muscle during the HD session, three times a week, for 8 weeks in NMESG. DNA damage in blood was evaluated by the alkaline comet assay prior to follow-up, after 4 and 8 weeks of intervention. RESULTS: Intradialytic NMES in CKF patients induced a significant decrease in DNA damage after four [49.9 (3.68) vs 101.5 (6.53); p = 0.000] than eight [19.9 (2.07) vs 101.5 (6.53); p = 0.000] weeks compared to baseline. Genomic damage was also significantly less after four [NMESG: 49.9 (3.68) vs CG: 92.9 (12.61); p = 0.001] than after eight [NMESG: 19.9 (2.07) vs CG: 76.4 (11.15); p = 0.000] weeks compared to CG. CONCLUSIONS: This study demonstrates for the first time that intradialytic NMES is able to reduce DNA damage in blood of CKF patients.

Effects of Intradialytic Neuromuscular Electrical Stimulation on Strength and Muscle Architecture in Patients With Chronic Kidney Failure: Randomized Clinical Trial.

This study aimed to evaluate the effects of neuromuscular electrical stimulation (NMES) on muscle strength and architecture, functional capacity, and endothelial function in patients with chronic kidney failure (CKF) on hemodialysis (HD). Twenty-one patients with CKF on HD were randomized into a control group (CG; n = 10) and neuromuscular electrical stimulation group (NMESG; n = 11) who received NMES in the quadriceps muscle for 8 weeks, 3 times/week (20-34 min) during HD sessions. The muscle strength of the lower limbs was evaluated by dynamometry and sit-and-stand test (SST); muscle architecture through ultrasonography; functional capacity by the distance covered in a 6-min walk test and the endothelial function by flow-mediated dilatation technique of the brachial artery. There was an increase in the strength of the lower limbs in the NMESG compared to the CG (dynamometry: 43.28 ± 16.94 vs. 35.84 ± 16.89, P = 0.006; SST: 16.10 ± 6.51 vs. 12.50 ± 4.7, P = 0.029). There was a significant reduction in pennation angles of the right vastus lateralis (RVL) and left vastus lateralis (LVL) in the CG when compared to the NMESG (RVL: 11.93 [10.70-15.11] vs. 13.57 [11.81-15.96], P = 0.039; LVL: 11.62 [9.00-14.20] vs. 15.52 [12.86-20.02], P = 0.042). There was no change in functional capacity and in the endothelial function for CG and NMESG, respectively. In conclusion, NMES increases muscle strength and has a protective effect against muscle atrophy of the lower limbs of patients with chronic kidney failure on HD.

Associação entre função endotelial e balanço autonômico em indivíduos saudáveis (y modulación autonómica en sujetos sanos) / Association between endothelial function and autonomic balance in healthy subjects

Objetivo: Avaliar a associação da função endotelial com o balanço autonômico, variáveis antropométricas e bioquímicas em indivíduos saudáveis (Evaluar la asociación de la función endotelial con el equilibrio autónomo, variables antropométricas y bioquímicas en sujetos sanos). Metodologia: Estudo transversal com 35 voluntários normotensos, ativos e muito ativos, de ambos os sexos (27.5 ± 5.8 anos de idade). O balanço autonômico foi estimado pela medida da variabilidade da frequência cardíaca, com o Polar RS800CX, por 20 minutos (10 minutos em ventilação espontânea/10 minutos com ventilação controlada). O sinal foi analisado pelo (La señal se analizó con el) software Kubios Heart Rate Variability. A frequência respiratória foi fixada em um (La frecuencia respiratoria se estableció con un) metrônomo ajustado a 12 irpm. A função endotelial foi avaliada por ultrassonografia da artéria braquial e estimada pela dilatação mediada pelo fluxo. Resultados: Houve correlação negativa entre a dilatação mediada pelo fluxo e a relação (Hubo una correlación negativa entre la dilatación mediada por el flujo y la relación) LF/HF (r = -0.43; p = 0.011), componente de baixa frequência (componente de baja frecuencia) (LF; r = -0.41; p = 0.016), índice de massa corporal (r = -0.43; p = 0.01) e peso (r = -0.39; p = 0.02). A dilatação mediada pelo fluxo esteve associada com o componente de alta frequência (HF; r = 0.41; p = 0.015). Não houve associação da dilatação mediada pelo fluxo ou de componentes do balanço autonômico (hubo una asociación de la dilatación mediada por flujo o de los componentes del equilibrio autonómico) com colesterol total, glicemia e triglicerídeos. Conclusão: A associação da função endotelial com o balanço autonômico em sujeitos saudáveis, ativos e muito ativos, demonstra a ação simultânea entre respostas biológicas das células endoteliais e estímulos neurohumorais do sistema nervoso autônomo, ambos visando o adequado controle cardiovascular (ambos con vistas al adecuado control cardiovascular).

Objective: To evaluate the association between endothelial function and autonomic balance, anthropometric and biochemical variables in healthy subjects. Methods: Cross-sectional study with 35 normotensive, active and very active volunteers of both sexes (27.5 ± 5.8 years). Autonomic balance was estimated by measuring heart rate variability, with the Polar RS800CX, for 20 minutes (10 minutes in spontaneous ventilation/10 minutes with controlled ventilation). The signal was analyzed by Kubios Heart Rate Variability software. Respiratory rate was fixed on a metronome set at 12 breaths/min. Endothelial function was assessed by ultrasound of the brachial artery and estimated by flow-mediated dilation. Results: There was a negative correlation between flow-mediated dilation and LF/HF ratio (r = -0.43; p = 0.011), low frequency component (LF; r = -0.41; p = 0.016), body mass index (r = -0.43; p = 0.01) and weight (r = -0.39; p = 0.02). Flow-mediated dilation was associated with the high-frequency component (HF, r = 0.41; p = 0.015). There was no association between flow-mediated dilation or components of the autonomic balance and total cholesterol, blood glucose and triglycerides. Conclusion: The association between endothelial function and autonomic balance in healthy, active and very active subjects demonstrates the simultaneous action between biological responses of endothelial cells and neuro-humoral stimuli of the autonomic nervous system, both with a view to proper cardiovascular control.

VEGF gene therapy cooperatively recruits molecules from the immune system and stimulates cell homing and angiogenesis in refractory angina.

BACKGROUND: New vessels are formed in response to stimuli from angiogenic factors, a process in which paracrine signaling is fundamental. OBJECTIVE: To investigate the cooperative paracrine signaling profile in response to Vascular Endothelial Growth Factor (VEGF) gene therapy in patients with coronary artery disease (CAD) and refractory angina. METHOD: A cohort study was conducted in which plasma was collected from patients who underwent gene therapy with a plasmid expressing VEGF 165 (10) and from surgical procedure controls (4). Blood samples were collected from both groups prior to baseline and on days 3, 9 and 27 after the interventions and subjected to systemic analysis of protein expression (Interleukin-6, IL-6; Tumor Necrosis Factor-α, TNF-α; Interleukin-10, IL-10; Stromal Derived Factor-1 α, SDF-1α; VEGF; Angiopoietin-1, ANGPT-1; and Endothelin-1, ET-1) using the enzyme-linked immunosorbent assay (ELISA). RESULTS: Analysis showed an increase in proinflammatory IL-6 (p=0.02) and ET-1 (p=0.05) on day 3 after gene therapy and in VEGF (p=0.02) on day 9. A strong positive correlation was found between mobilization of endothelial progenitor cells and TNF-α on day 9 (r=0.71; p=0.03). Furthermore, a strong correlation between ß-blockers, antiplatelets, and vasodilators with SDF-1α baseline in the group undergoing gene therapy was verified (r=0.74; p=0.004). CONCLUSION: Analysis of cooperative paracrine signaling after VEGF gene therapy suggests that the immune system cell and angiogenic molecule expression as well as the endothelial progenitor cell mobilization are time-dependent, influenced by chronic inflammatory process and continuous pharmacological treatment.

Efeitos Agudos da Estimulação Elétrica Funcional e do Treinamento Muscular Inspiratório em Pacientes com Insuficiência Cardíaca: Ensaio Clínico Randomizado Cruzado / Acute Effects of Functional Electrical Stimulation and Inspiratory Muscle Training in Patients With Heart Failure: A Randomized Crossover Clinical Trial

Fundamentos: A insuficiência cardíaca é uma doença multissistêmica que inclui disfunção autonômica. Objetivo: Avaliar os efeitos agudos da Estimulação Elétrica Funcional (EEF) e do Treinamento Muscular Inspiratório (TMI) sobre o controle autonômico, a função endotelial e os níveis de citocinas inflamatórias em pacientes portadores de IC. Métodos: Estudo randomizado cruzado que incluiu 12 pacientes submetidos a três intervenções randomizadas: EEF, TMI, e EEF + TMI, com intervalo de 1 semana entre as sessões. O TMI foi realizado durante 15 minutos, com 30% da pressão inspiratória máxima. A EEF foi realizada nos músculos vasto lateral e vasto medial, a uma frequência de 20Hz durante 30 minutos. O controle autonômico foi medido através de monitorização de pressão batimento por batimento (Finapres); a função endotelial, através da técnica de dilatação mediada por fluxo (DMF); e os níveis de citocinas inflamatórias foram medidos antes e depois de cada sessão. Resultados: O controle autonômico após EEF diminuiu em termos de BF/AF (p=0,01) e BFn.u (p=0,03), e aumentou em termos de RR médio (p=0,005). Observou-se um aumento do RR médio após o TMI (p=0,005) e após EEF+TMI (p=0,02). Não houve diferenças na DMF e na concentração de lactato sérico. Quanto às citocinas, a EEF promoveu uma redução nos níveis de TNF-α (pré versus pós 24 horas, p = 0,05). O TMI resultou em níveis aumentados de IL-10 (pré versus 24 horas pós, p=0,05) e em níveis diminuídos de TNF-α (1 hora pós versus 24 horas pós, p = 0,03). Não houve diferenças quando as duas intervenções foram associadas. Conclusão: EEF, TMI, e EEF + TMI alteraram o controle autonômico, mas não a função endotelial. A EEF e o TMI isoladamente alteraram os níveis de citocinas inflamatórias. Ensaios Clínicos: NCT01325597

Background: Heart Failure is a multisystem disorder, which includes autonomic dysfunction. Objective: To evaluate the acute effects of Functional Electrical Stimulation (FES) and Inspiratory Muscle Training (IMT) on autonomic control, endothelial function and inflammatory cytokine levels in patients with HF. Methods: Randomized crossover trial including 12 patients undergoing three randomized interventions: FES, IMT, and FES+IMT, with a 1-week interval between sessions. IMT was performed for 15 minutes with 30% of the maximal inspiratory pressure. FES was performed in the vastus lateralis and vastus medialis muscles, at 20Hz for 30 minutes. The autonomic control was measured using beat-to-beat blood pressure monitoring (Finapres); the endothelial function, using the flow-mediated dilation technique (FMD); and inflammatory cytokine levels were assessed before and after the sessions. Results: Autonomic control after FES decreased regarding LF/HF (p=0.01) and LFn.u (p=0.03), and increased regarding mean RR (p=0.005). Increased mean RR was observed after IMT (p=0.005) and after FES+IMT (p=0.02). No differences were found in FMD and blood lactate concentration. As regards the cytokines, FES led to a decrease in TNF-α levels (pre vs. 24 hours post, p = 0.05). IMT resulted in increased IL-10 levels (pre vs. 24 hours post, p=0.05) and decreased TNF-α levels (1 hour post vs. 24 hours post, p = 0.03). No difference was observed when the two interventions were associated. Conclusion: FES, IMT, and FES+IMT changed the autonomic control without changing the endothelial function. FES and IMT separately changed inflammatory cytokine levels. Clinical Trials: NCT01325597

Treinamento (Entrenamiento) muscular inspiratório para o controle (el control) autonômico de indivíduos saudáveis (sanos) / Inspiratory muscle training in autonomic control in healthy individuals

Verificar o efeito (el efecto) agudo de diferentes sobrecargas de treinamento (entrenamiento) muscular inspiratório (TMI) sobre a (la) modulação autonômica cardiovascular em indivíduos saudáveis.Métodos: Ensaio (Ensayo) clínico randomizado cruzado. Foram (Fueron) incluídos voluntários saudáveis (sanos) entre 18 e 35 anos. A variabilidade da (de la) frequência cardíaca (VFC) foi analisada antes e após o (y después del) TMI a os (a los) 10 minutos, 60 minutos e 24 horas (agudo, subagudo e tardio, respectivamente). A força (La fuerza) muscular inspiratória foi avaliada (fue evaluada) através da (de la)medida de pressão inspiratória máxima (PImáx) com a utilização do (del) manovacuômetro digital MVD300 (Microhard System®, Globalmed, Porto Alegre, Brasil). O TMI foi realizado à 30% e 60% da PImáx ajustados no (en el) dispositivo pressórico linear Power breathe®. Resultados: Foram avaliados dezenove (diecinueve) indivíduos (47% homens, 25 ± 5 anos). Na (En la) fase aguda apenas com 60% da PImá houve redução (hubo una reducción) significativa da variabilidade dos (de los) intervalos RR e no (y enel) componente de alta frequência (HFnu), en quanto que o (mientras que el) componente de baixa(baja) frequência (LFnu) e o balanço (y el equilibrio) autonômico (LF/HF) aumentaram significativamente.Na (En la) fase subaguda, o mesmo comportamento foi observado para HFnu, LFnu, LF/HF. Quando comparadas as (Cuando se compararon las) sobrecargas, houve (hubo) aumento significativo na (en la) magnitude do efeito a 60% PImáx para NN50, LF/HF, LFnu, HFnu na fase aguda, bem como, para (así como para) RR, NN50, LFnu e HFnu na fase subaguda (p < 0.05). Conclusão: Agudamente, o efeito doTMI à 60% da PImáx foi maior deslocando a (fue más grande, desplazando la) modulação autonômicado sistema cardiovascular em indivíduos saudáveis para um predomínio simpático...

Effects of therapeutic ultrasound on haematological dynamics and fibrinogen during the inflammatory phase after muscle injury in rats / Efeitos do ultrassom terapêutico na dinâmica hematológica e no fibrinogênio durante a fase inflamatória após lesão muscular em ratos

This study investigated the effects of ultrasound therapy on haematological dynamics and plasma fibrinogen during the inflammatory phase of muscle injury. Forty-eight male Wistar rats were divided into control group (CG), continuous ultrasound treated group (CTU) and pulsed ultrasound (PTU). Animals were subjected to surgical incision. A transverse lesion was made in the biceps femoris muscle (50%). CTU (1.0 MHz) was applied at 12-hour intervals on the lesion, for three days, with 0.4 W cm-2 and three minutes of duration (six applications in the total). PTU was applied in the pulsed mode 20% (2 ms on/8 ms off), maintaining the other parameters. Fibrinogen, white and red blood cells were analyzed in the 24th, 48th and 72nd hour after the injury. PTU has reduced fibrinogen levels by 20% at the 24thh and by 30% at the 48thh (p < 0.001) and haemoglobin reduction at the 72nd hour (p < 0.001), which had already occurred during the 2nd collection in the other groups. CTU favoured erythrocyte reduction at the 48th h (p = 0.003). PTU presented an anti-inflammatory effect due to plasma fibrinogen reduction, and CTU favored haemorrhage due to the reduction of erythrocytes when applied in the first 72 hours after muscle injury.

O objetivo desta pesquisa foi investigar os efeitos do ultrassom terapêutico na dinâmica hematológica e no fibrinogênio plasmático durante a fase inflamatória de lesão muscular. Quarenta e oito ratos Wistar foram divididos em grupo controle (CG), grupo tratado com ultrassom contínuo (CTU) e tratado com ultrassom pulsado (PTU). Os animais foram submetidos a uma incisão cirúrgica. A lesão transversal (50%) foi realizada no músculo bíceps femoral. O CTU (1,0 MHz) foi aplicado sobre a lesão em intervalos de 12h, por três dias, a 0,4 W cm-2 e duração de 3 min. (total de 6 aplicações). O PTU foi aplicado em modo de pulso de 20% (2 ms on/8 ms off) mantido os demais parâmetros. O fibrinogênio e as células sanguíneas brancas e vermelhas foram avaliados na 24ª, 48ª e 72ªh após a lesão. O PTU reduziu os níveis plasmáticos do fibrinogênio em 20% na 24ªh e 30% na 48ªh (p < 0,001), a hemoglobina apresentou uma redução na 72ªh (p < 0,001), sendo que nos outros grupos isso ocorreu na 2ª coleta. O CTU favorece a redução dos eritrócitos na 48ªh (p = 0,003). O PTU apresenta efeito anti-inflamatório pela redução plasmática do fibrinogênio e o CTU favorece a hemorragia pela redução dos eritrócitos quando aplicados nas primeiras 72h após lesão muscular.

Continuous blood pressure response at different intensities in leg press exercise.

BACKGROUND: Generally, the evaluation of the blood pressure response to resistance exercise has been limited to the evaluation of discontinuous casual blood pressure monitoring, often measured at the end of the exercise. DESIGN: To continuously evaluate the blood pressure response at different intensities of leg press exercise with the same duration and number of repetitions. METHODS: Seven normotensive healthy men performed an incremental test on the leg press machine at relative intensities of one repetition maximum (1RM). The blood pressure and heart rate were measured simultaneously to the incremental exercise by a photoplethysmographic method. RESULTS: The mean ± SD peak values of the heart rate, diastolic blood pressure (DBP) and systolic blood pressure (SBP) were obtained on 70% of 1RM and were 145 ± 20 bpm, 113.1 ± 15.4 mmHg, and 192.4 ± 20.0 mmHg, respectively. The SBP was characterized by a decrease followed by an increase during the sets of exercise. The decrease in the SBP was 12-22 mmHg and took approximately 25 seconds to reach the minimum value before the increase. It was observed for all participants in most of the intensities. The rate of increase in the SBP was not statistically different between the intensities. CONCLUSIONS: Both duration and intensity of exercise have an impact on the blood pressure response. Above 30% of 1RM, the SBP decreases in approximately 20 seconds and starts to increase until the end of the set of leg press exercise.

Higher mean blood pressure is associated with autonomic imbalance but not with endothelial dysfunction in young soccer players.

BACKGROUND: Blood pressure (BP) should be kept within a narrow range to allow adequate tissue perfusion. In particular, heart-rate variability (HRV) can be used to assess autonomic cardiovascular modulation, and flow-mediated dilation (FMD) can provide valuable information about the ability of the cardiovascular system to adapt to different pressures. Our objective in the study described here was to investigate the effect of a difference of 10mm Hg in mean arterial pressure (MAP) on endothelial function and autonomic balance in young and normotensive soccer players. METHODS: Twenty-nine young male soccer players (mean age 17.7 years) were divided into two groups according to their MAP (mm Hg): MAP-84 and MAP-94. The BP, FMD, HRV and maximum oxygen uptake (VO2max) of each group were measured. RESULTS: Systolic BP (SBP) and diastolic BP (DBP) were significantly higher (P < 0.0001 and P < 0.006, respectively) in the MAP-94 group. There were no differences in VO2max and endothelial function in the two groups (P < 0.7699). However, the standard deviation (SD) of normal RR intervals (SDNN) and the square root of the mean squared differences in successive RR intervals (RMSSD) were significantly lower in the MAP-94 than in the MAP-84 group (P < 0.0001 and P < 0.005, respectively). In the MAP-94 group, both the high-and low-frequency components were significantly (P < 0.001, P < 0.021, P < 0.017, respectively) lower in both absolute and normalized units, whereas the LF/HF ratio was significantly (P < 0.012) higher. CONCLUSIONS: Collectively, our findings indicate that in young soccer players, autonomic cardiovascular modulation is impaired when MAP is increased by 10mm Hg, even within an optimal range of BP and regardless of endothelial function and VO2max.

Terapia gênica com fator de crescimento endotelial vascular 165 para pacientes com angina refratária: mobilização de células progenitoras endoteliais / VEGF 165 gene therapy for patients with refractory angina: mobilization of endothelial progenitor cells

FUNDAMENTO: O fator de crescimento endotelial vascular (VEGF - vascular endothelial growth factor) induz a mobilização de células progenitoras endoteliais (CPEs) com capacidade de proliferação e diferenciação em células endoteliais, contribuindo, dessa forma, para o processo angiogênico. OBJETIVO: Buscamos avaliar o comportamento de CPEs em pacientes com doença cardíaca isquêmica e angina refratária que receberam injeções intramiocardicas de 2000 µg de VEGF165 como terapia única. MÉTODOS: O estudo foi uma subanálise de um ensaio clínico. Pacientes com doença cardíaca isquêmica avançada e angina refratária foram avaliados para inclusão no estudo. Os critérios de inclusão foram: sinais e sintomas de angina e/ou insuficiência cardíaca apesar de tratamento medicamentoso máximo e área de isquemia miocárdica de, no mínimo, 5% conforme avaliado por uma tomografia computadorizada por emissão de fóton único (TCEFU). Os critérios de exclusão foram: idade > 65 anos, fração de ejeção do ventrículo esquerdo < 25% e cancer diagnosticado. Os pacientes cujos níveis de CPE foram avaliados foram incluídos. A intervenção consistiu na administração de 2000 µg de VEGF 165 de plasmídeo injetado no miocárdio isquêmico. A frequência de células CD34+/KDR+ foi analisada por citometria de fluxo antes e 3, 9, e 27 dias após a intervenção. RESULTADOS: Um total de 9 pacientes foram incluídos, 8 homens, média de idade de 59,4 anos, fração de ejeção ventricular esquerda de 59,3%, e classe de angina predominante III. Observou-se um aumento significativo dos níveis de CPEs no terceiro dia após a intervenção. Todavia, 9 e 27 dias após a intervenção, os níveis de CPEs foram similares aos basais. CONCLUSÃO: Identificamos uma mobilização transitória de CPE, com pico no terceiro dia após a intervenção com VEGF 165 em pacientes com angina refratária. Todavia, os níveis de CPEs apresentaram-se semelhantes aos basais 9 e 27 dias após a intervenção.

BACKGROUND: Vascular endothelial growth factor (VEGF) induces mobilization of endothelial progenitor cells (EPCs) with the capacity for proliferation and differentiation into mature endothelial cells, thus contributing to the angiogenic process. OBJECTIVE: We sought to assess the behavior of EPCs in patients with ischemic heart disease and refractory angina who received an intramyocardial injections of 2000 µg of VEGF 165 as the sole therapy. METHODS: The study was a subanalysis of a clinical trial. Patients with advanced ischemic heart disease and refractory angina were assessed for eligibility. Inclusion criteria were as follows: signs and symptoms of angina and/or heart failure despite maximum medical treatment and a myocardial ischemic area of at least 5% as assessed by single-photon emission computed tomography (SPECT). Exclusion criteria were as follows: age > 65 years, left ventricular ejection fraction < 25%, and a diagnosis of cancer. Patients whose EPC levels were assessed were included. The intervention was 2000 µg of VEGF 165 plasmid injected into the ischemic myocardium. The frequency of CD34+/KDR+ cells was analyzed by flow cytometry before and 3, 9, and 27 days after the intervention. RESULTS: A total of 9 patients were included, 8 males, mean age 59.4 years, mean left ventricular ejection fraction of 59.3% and predominant class III angina. The number of EPCs on day 3 was significantly higher than that at baseline (p = 0.03); however, that on days 9 and 27 was comparable to that at baseline. CONCLUSION: We identified a transient mobilization of EPCs, which peaked on the 3th day after VEGF 165 gene therapy in patients with refractory angina and returned to near baseline levels on days 9 and 27.

VEGF 165 gene therapy for patients with refractory angina: mobilization of endothelial progenitor cells.

BACKGROUND: Vascular endothelial growth factor (VEGF) induces mobilization of endothelial progenitor cells (EPCs) with the capacity for proliferation and differentiation into mature endothelial cells, thus contributing to the angiogenic process. OBJECTIVE: We sought to assess the behavior of EPCs in patients with ischemic heart disease and refractory angina who received an intramyocardial injections of 2000 µg of VEGF 165 as the sole therapy. METHODS: The study was a subanalysis of a clinical trial. Patients with advanced ischemic heart disease and refractory angina were assessed for eligibility. Inclusion criteria were as follows: signs and symptoms of angina and/or heart failure despite maximum medical treatment and a myocardial ischemic area of at least 5% as assessed by single-photon emission computed tomography (SPECT). Exclusion criteria were as follows: age > 65 years, left ventricular ejection fraction < 25%, and a diagnosis of cancer. Patients whose EPC levels were assessed were included. The intervention was 2000 µg of VEGF 165 plasmid injected into the ischemic myocardium. The frequency of CD34+/KDR+ cells was analyzed by flow cytometry before and 3, 9, and 27 days after the intervention. RESULTS: A total of 9 patients were included, 8 males, mean age 59.4 years, mean left ventricular ejection fraction of 59.3% and predominant class III angina. The number of EPCs on day 3 was significantly higher than that at baseline (p = 0.03); however, that on days 9 and 27 was comparable to that at baseline. CONCLUSION: We identified a transient mobilization of EPCs, which peaked on the 3th day after VEGF 165 gene therapy in patients with refractory angina and returned to near baseline levels on days 9 and 27.

Association between endothelial function and autonomic modulation in patients with Chagas disease.

BACKGROUND: Under homeostatic condition, the autonomic nervous system (ANS), through the release of vasoconstrictor neurotransmitters, and the endothelium, through the release of vasodilating substances, interact to maintain blood vessel tone. However, the association between those two systems in patients with Chagas disease in its indeterminate phase (IChD) has not been studied. OBJECTIVE: To assess the association between autonomic modulation parameters and endothelial function in patients with IChD. METHODS: Thirteen patients with IChD (59.2 ± 11.23 years) and no risk factors for cardiovascular disease were assessed for autonomic modulation by using the blood pressure oscillometric method (Finapress) and the heart rate variability technique (HRV) in the frequency domain. Endothelial function was assessed by use of the brachial artery flow-mediated dilation (FMD) method with high-resolution ultrasound images. RESULTS: In the dorsal decubitus position, correlation of FMD was observed with normalized high-frequency (r = 0.78; p = 0.007) and low-frequency spectral components (r = 0.68; p = 0.01), as well as with sympathovagal balance (r = -0.78; p = 0.004). CONCLUSIONS: Our study indicates the existence of a relationship between the changes in autonomic modulation and endothelial function in patients with IChD.

Associação entre função endotelial e a modulação autonômica em pacientes com doença de chagas / Association between endothelial function and autonomic modulation in patients with chagas disease

FUNDAMENTO: Em condição homeostática, o Sistema Nervoso Autônomo (SNA), pela liberação de neurotransmissores vasoconstritores, e o endotélio, pela liberação de substâncias vasodilatadoras, atuam em sintonia para manter o tônus vascular. Todavia, a associação entre esses dois sistemas em portadores da doença de Chagas na forma indeterminada (DChI) ainda não foi estudada. OBJETIVO: Verificar a associação entre parâmetros referentes à modulação autonômica e à função endotelial em portadores da DChI. MÉTODOS: Treze pacientes com DChI (59,2 ± 11,23 anos) sem fatores de risco para doença cardiovascular foram avaliados para modulação autonômica pelo método oscilométrico da pressão arterial (Finapress) e a análise dos registros mediante a técnica da Variabilidade da Frequência Cardíaca (VFC) no domínio da frequência. A função endotelial foi avaliada pelo método de dilatação mediada pelo fluxo da artéria braquial (DMF), usando imagens de ultrassom de alta resolução. RESULTADOS: Na posição em decúbito dorsal foi observada correlação entre os componentes espectrais de alta (HF) (r = 0,78 p = 0,007) e baixa (LF) frequências normalizadas (r = 0,68 p = 0,01), bem como com o balanço simpatovagal (LF/HF) (r= -0,78 p = 0,004) com a DMF. CONCLUSÃO: Nosso estudo aponta a existência de uma relação entre as alterações na modulação autonômica e na função endotelial em pacientes com Doença de Chagas na forma indeterminada.

BACKGROUND: Under homeostatic condition, the autonomic nervous system (ANS), through the release of vasoconstrictor neurotransmitters, and the endothelium, through the release of vasodilating substances, interact to maintain blood vessel tone. However, the association between those two systems in patients with Chagas disease in its indeterminate phase (IChD) has not been studied. OBJECTIVE: To assess the association between autonomic modulation parameters and endothelial function in patients with IChD. METHODS: Thirteen patients with IChD (59.2 ± 11.23 years) and no risk factors for cardiovascular disease were assessed for autonomic modulation by using the blood pressure oscillometric method (Finapress) and the heart rate variability technique (HRV) in the frequency domain. Endothelial function was assessed by use of the brachial artery flow-mediated dilation (FMD) method with high-resolution ultrasound images. RESULTS: In the dorsal decubitus position, correlation of FMD was observed with normalized high-frequency (r = 0.78; p = 0.007) and low-frequency spectral components (r = 0.68; p = 0.01), as well as with sympathovagal balance (r = -0.78; p = 0.004). CONCLUSIONS: Our study indicates the existence of a relationship between the changes in autonomic modulation and endothelial function in patients with IChD.

Prognostic value of the six-minute walk test in end-stage renal disease life expectancy: a prospective cohort study.

OBJECTIVES: The six-minute walk test has been widely used to evaluate functional capacity and predict mortality in several populations. Thus, the aim of this study was to evaluate the prognostic value of the six-minute walk test for the life expectancy of end-stage renal disease patients. METHODS: Patients over 18 years old who underwent hemodialysis for at least six months were included. Patients with hemodynamic instability, smoking, chronic obstructive pulmonary disease, physical incapacity and acute myocardial stroke in the preceding three months were excluded. RESULTS: Fifty-two patients (54% males; 36+11 years old) were followed for 144 months. The distance walked in the six-minute walk test was a survival predictor for end-stage renal disease patients. In the multivariate analysis, for each 100 meters walked with a 100-meter increment, the hazard ratio was 0.53, with a 95% confidence interval of 0.37-0.74. There was a positive correlation between the distance walked in the six-minute walk test and peak oxygen consumption (r = 0.508). In the multivariate analysis, each year of dialysis treatment represented a 10% increase in death probability; in the severity index analysis, each point on the scale represented an 11% increase in the death risk. CONCLUSIONS: We observed that survival increased approximately 5% for every 100 meters walked in the six-minute walk test, demonstrating that the test is a viable option for evaluating the functional capacity in patients with end-stage renal disease.